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ISSN 1027-0299 Recognised and registered with the Pakistan Medical & Dental Council NO.PF.11-F-96 (Infectious Diseases) 2560 College of Physicians & Surgeons, Pakistan Indexed - WHO EMRO 69 73 68 October - December 2019 Volume 28 Issue 04 INFECTIOUS DISEASES JOURNAL Published by the Medical Microbiology & Infectious Diseases Society of Pakistan of Pakistan I D J Oct - Dec 2019. 67 Volume 28 Issue 04 Volume 28 Issue 04 CONTENTS PAGE # Rights: No part of this issue or associated program may be reproduced, transmitted, transcribed, stored in a retrieval system or translated into language or computer language in any form or means, electronic, mechanical, magnetic, optical, chemical, manual or otherwise without the express permission of the editor/publisher and author(s) of IDJ. Disclaimer: Statements and opinions expressed in the articles, news, letters to the editors and any communications herein are those of the author(s), the editor and the publisher disclaim any responsibility or liability for such material. Neither the editor nor publisher guarantee, warrant, or endorse any product or service advertised in their publication, nor do they guarantee any claim made by the manufacturers of such product or service. Submission: Infectious Diseases Journal (IDJ) is published quarterly. Please submit manuscripts at [email protected]. See author guidelines. Designed & Published by: Medishine Publications A-452, Ground Floor, Block 7, K.A.E.C.H.S, Karachi. Tel:34555263, E-mail:[email protected] Proprietor: Medical Microbiology & Infectious Diseases Society of Pakistan 21 G /1, Block - 6, P.E.C.H.S., Shahrah-e-Faisal, Karachi. Ph: 0333-3977011 E-mail: [email protected] Infectious Diseases Journal of Pakistan Official Organ of the Medical Microbiology & Infectious Diseases Society of Pakistan President Bushra Jamil Internal Medicine, Infectious Diseases Aga Khan University Hospital, Karachi. Pakistan Gen. Secretary Summiya Nizamuddin Section of Microbiology Shaukat Khanum Memorial Cancer Hsopital and Research Centre, Lahore, Pakistan. Treasurer Sunil Dodani Department of Infectious Diseases, Sindh Institute of Urology & Transplantation Karachi, Pakistan Editorial Office Editor: Ali Faisal Saleem Associate Editors: Iffat Khanum Kiran Habib Muhammad Idris Mazhar Sunil Dodani Nosheen Nasir Editorial Board: Aamer Ikram Naseem Salahuddin Altaf Ahmed Ejaz A. Khan Shehla Baqi Luqman Setti M. Asim Beg Naila Baig Ansari Rana Muzaffar 78 Manager MMIDSP: Luqman Mahmood 85 87 EDITORIAL Role of Digital Health for Ceftriaxone-Resistant Salmonella Outbreak Investigation and Control in Sindh Province, Pakistan Abdul Momin Kazi ORIGINAL ARTICLES Does Abnormal Serum Glucose Level Compromise the Outcome in Neonatal Sepsis? Muhammad Usman Khalid, Farah Haroon, Sikandar Hayat, Rafia Gul, Khawaja Ahmad Irfan Waheed, Javaria Younus Socioeconomic Status of Father and Vaccination Status of Children: A Community Based Household Survey Naureen Omar, Shamaila Hassnain, Umbreen Navied, Iram Manzoor Emergence of Multidrug Resistant Gram-negative Pathogens in an Intensive Care Unit of a Tertiary Care Hospital Zehra NM, Hanif F, Khursheed U, Jaffer SR, Yousuf S, Nadeem S CASE REPORT Extremely Drug Resistant Pseudomonas in Qazi Hussain Ahmed Medical Complex, Nowshera, Pakistan. Hamzullah Khan, Fazli Bari INSTRUCTIONS FOR AUTHORS Courtesy : Ali Faisal Saleem, Assistant professor, Paediatric Infectious Diseases, Aga Khan University, Karachi, Pakistan A 13-year-old girl with fever, weight loss, poor intake and lethargies. Family of Pulmonary tuberculosis s present Upper lung infiltrates are identified in anterior segment of left upper lobe showing calcifications. Left apical infiltrates also noted. A tiny calcified granuloma is identified involving the posterior segment of the left lower lobe. No evidence of pleural effusion or pneumothorax identified bilaterally. Central tracheobronchial tree appears unremarkable. Left upper lobe infiltrates with calcifications. Findings could represent granulomatous infection likely tuberculosis. a b c

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  • ISSN 1027-0299Recognised and registered with thePakistan Medical & Dental CouncilNO.PF.11-F-96 (Infectious Diseases) 2560College of Physicians & Surgeons, PakistanIndexed - WHO EMRO

    69

    73

    68

    October - December 2019 Volume 28 Issue 04

    INFECTIOUSDISEASESJOURNALPublished by the Medical Microbiology & Infectious Diseases Society of Pakistan

    of Pakistan

    IDJ

    Oct - Dec 2019. 67Volume 28 Issue 04Volume 28 Issue 04

    CONTENTS PAGE #

    Rights:No part of this issue or associated program may be reproduced, transmitted,transcribed, stored in a retrieval system or translated into language orcomputer language in any form or means, electronic, mechanical, magnetic,optical, chemical, manual or otherwise without the express permission ofthe editor/publisher and author(s) of IDJ.

    Disclaimer:Statements and opinions expressed in the articles, news, letters to the editorsand any communications herein are those of the author(s), the editor and thepublisher disclaim any responsibility or liability for such material. Neitherthe editor nor publisher guarantee, warrant, or endorse any product orservice advertised in their publication, nor do they guarantee any claimmade by the manufacturers of such product or service.

    Submission:Infectious Diseases Journal (IDJ) is published quarterly. Please submit manuscriptsat [email protected]. See author guidelines.

    Designed & Published by:Medishine PublicationsA-452, Ground Floor, Block 7, K.A.E.C.H.S, Karachi.Tel:34555263, E-mail:[email protected]

    Proprietor:Medical Microbiology & Infectious Diseases Society of Pakistan21 G /1, Block - 6, P.E.C.H.S., Shahrah-e-Faisal, Karachi. Ph: 0333-3977011E-mail: [email protected]

    Infectious Diseases Journal of PakistanOfficial Organ of the

    Medical Microbiology & Infectious Diseases Society of Pakistan

    President Bushra JamilInternal Medicine, Infectious DiseasesAga Khan University Hospital,Karachi. Pakistan

    Gen. Secretary Summiya NizamuddinSection of MicrobiologyShaukat Khanum Memorial Cancer Hsopitaland Research Centre, Lahore, Pakistan.

    Treasurer Sunil DodaniDepartment of Infectious Diseases,Sindh Institute of Urology & TransplantationKarachi, Pakistan

    Editorial Office

    Editor: Ali Faisal Saleem

    Associate Editors: Iffat KhanumKiran HabibMuhammad Idris MazharSunil DodaniNosheen Nasir

    Editorial Board: Aamer Ikram Naseem SalahuddinAltaf Ahmed Ejaz A. KhanShehla Baqi Luqman SettiM. Asim Beg Naila Baig Ansari

    Rana Muzaffar

    78

    Manager MMIDSP: Luqman Mahmood85

    87

    EDITORIAL

    Role of Digital Health for Ceftriaxone-Resistant SalmonellaOutbreak Investigation and Control in Sindh Province, PakistanAbdul Momin Kazi

    ORIGINAL ARTICLES

    Does Abnormal Serum Glucose Level Compromise the Outcomein Neonatal Sepsis?Muhammad Usman Khalid, Farah Haroon, Sikandar Hayat, Rafia Gul,Khawaja Ahmad Irfan Waheed, Javaria Younus

    Socioeconomic Status of Father and Vaccination Status of Children:A Community Based Household SurveyNaureen Omar, Shamaila Hassnain, Umbreen Navied, Iram Manzoor

    Emergence of Multidrug Resistant Gram-negative Pathogens inan Intensive Care Unit of a Tertiary Care HospitalZehra NM, Hanif F, Khursheed U, Jaffer SR, Yousuf S, Nadeem S

    CASE REPORT

    Extremely Drug Resistant Pseudomonas in Qazi Hussain AhmedMedical Complex, Nowshera, Pakistan.Hamzullah Khan, Fazli Bari

    INSTRUCTIONS FOR AUTHORS

    Courtesy : Ali Faisal Saleem, Assistant professor, Paediatric InfectiousDiseases, Aga Khan University, Karachi, Pakistan

    A 13-year-old girl with fever, weight loss, poor intake andlethargies. Family of Pulmonary tuberculosis s present

    Upper lung infiltrates are identified in anterior segment of leftupper lobe showing calcifications. Left apical infiltrates alsonoted. A tiny calcified granuloma is identified involving theposterior segment of the left lower lobe. No evidence of pleuraleffusion or pneumothorax identified bilaterally. Centraltracheobronchial tree appears unremarkable. Left upper lobeinfiltrates with calcifications. Findings could representgranulomatous infection likely tuberculosis.

    a b c

  • 68 . Infectious Diseases Journal of Pakistan

    GUEST EDITORIAL

    Role of Digital Health for Ceftriaxone-Resistant Salmonella Outbreak Investigation and Control inSindh Province, Pakistan

    In Nov 2016 the Clinical laboratory of Aga Khan UniversityHospital started reporting cases admitted at Aga Khan Maternal& Child Center Hyderabad with ceftriaxone resistant S. Typhi.This was the largest outbreak of ceftriaxone-resistant S Typhireported in Hyderabad, Pakistan. Given the urgency of theoutbreak and to understand attributable factors for the mode oftransmission it was decided to initiate an outbreak investigationwith epidemiological and technological support.

    With the leapfrog in mobile phone use, there has been a drasticincrease in access and acceptability of technology in bothdeveloped as well as developing countries. There is a greatpotential for digital health interventions to improve servicequality, provide information and decision support to healthprofessionals and improve visualization of data and therebyhaving a positive public health impact even in resourceconstrained settings.

    As part of an outbreak investigation an age-matched case-control (1:4) study was conducted from 1st December 2016 to15th September 2017. Further it was decided to use technologyat two fronts to support this study.1 To collect the participant’sinformation through eQuestionnaire and geotagging theirlocation.2 To conduct geospatial analysis in order to map outcases and understand mode of transmission. An open streetview map of Hyderabad was integrated in the Esri ArcGIS,version 10·5 to identify famous points and localities inHyderabad, using geospatial mapping technique. A paper-basedmap of Hyderabad sewerage line network was also acquiredfrom Hyderabad water board which was scanned andgeoreferenced in the ArcGIS software. In addition, co-ordinatesof the households for both cases and controls and importantrelevant landmarks including water supply were incorporated. Color coding of serum positive and negative cases, as well aswater positive cases, were also conducted.

    The geospatial analysis revealed a clustering of the cases aroundsewage lines both in Qasimabad and Latifabad areas inHyderabad indicating mixing of sewage water with municipalwater supply. Electronic mapping and microbiological analysisof community water supply samples from the drinking sourcealso indicated E-Coli contamination supporting our hypothesisof broken sewerage lines and mixing of sewerage water withthe drinking water; this was confirmed by molecular detectionof S. Typhi DNA by PCR. Data collected through mobilephone/tablet supported in generating geospatial maps andincorporation of information with Google maps and paper-based maps. This helped in identifying the specific distributionof the outbreak and in prediction of water born origin of bacteriathat was causing infection.

    Simultaneously spread of cases in Karachi from Hyderabadwere also identified and an algorithm was developed to extractgeographical location of the XDR typhi cases from AKU centrallaboratory data base according to towns in Karachi. This aidedin identifying clustering of XDR cases in Karachi and pointingout high burden areas. The geospatial data of Karachi alsoreinforced the evidence of spread to other cities of Sindhprovince. Our technique highlights the importance of usingdigital technology in a resource-constrained settings to improveroutine immunization coverage among Pakistani children andworldwide. One major limitation of the strategy used was thatthe culture positive cases were only from Aga Khan UniversityHospital main and satellite labs.

    In conclusion this was a unique digital health strategy which wasused for an outbreak investigation, following John Snow mappingtechnique for the Cholera epidemic but including latest informationand technology techniques. This study facilitated in formingCDC recommendations to travel to Pakistan and recommendationfor inclusion of TCV vaccine in the Expanded Program ofImmunization (EPI). This data aided in guiding the policy makersin understanding the reason of XDR spread through water born,direction of spread and identifying high burden areas for TCVvaccination campaigns and catch up doses. Future strategiesshould include adding culture positive XDR cases locationinformation from other major laboratories in Pakistan in the database and generating prediction models for spread of ceftriaxone-resistant Salmonella in Pakistan using geospatial, genomic,environmental and sero-prevalence data.

    AcknowledgementDr. Farah Qamar and Tahir Yousufzai.

    References1. Qamar FN, Yousafzai MT, Khalid M, Kazi AM, Lohana

    H, Karim S, Khan A, Hotwani A, Qureshi S, Kabir F, AzizF, Memon NM, Domki MH, Hasan R. Outbreak investigation ofceftriaxone-resistant Salmonella enterica serotype Typhi and its riskfactors among the general population in Hyderabad, Pakistan: a matchedcase-control study. Lancet Infect Dis. 2018 Dec;18(12):1368-1376.

    2. Yousafzai MT, Qamar FN, Shakoor S, Saleem K, LohanaH, Karim S, Hotwani A, Qureshi S, Masood N, Rauf M,Khanzada JA, Kazi M, Hasan R. Ceftr iaxone-resistantSalmonella Typhi Outbreak in Hyderabad City of Sindh,Pakistan: High Time for the Introduction of Typhoid Conjugate Vaccine.Clin Infect Dis. 2019 Feb 15;68 (Suppl1):S16-S21.

    Dr. Abdul Momin KaziAssistant Professor,Department of PaediatricsThe Aga Khan University, Karachi, PakistanEmail: [email protected]

  • Oct - Dec 2019. 69Volume 28 Issue 04

    ORIGINAL ARTICLE

    contributes 47% to U5MR.1 Its rate is 19 per 1,000 live birthsworldwide whereas in Pakistan it is 42 per 1,000 live births.2

    Neonatal sepsis is a significant cause of morbidity and mortalityand contributes up to 13% - 15% of deaths in developed, 30%- 50% deaths in developing countries and 28% neonatal deathsin Pakistan.3-5

    Neonatal sepsis is defined as the clinical syndrome with presenceof both infection and systemic inflammatory response.6 Clinicalvariables suggestive of sepsis are lethargy, feed intolerance,apnea, prolonged capillary refill time and hypotension alongwith variability in temperature, heart rate and respiratory rate.Laboratory parameters suggestive of sepsis include leukocytosis,leukopenia, raised C-reactive protein, Immature: Total neutrophilratio, thrombocytopenia, raised plasma lactate, raisedprocalcitonin, increase in IL-6 or IL-8, 16S PCR positive.7

    Whereas, blood culture is the gold standard for its diagnosis.8

    Sepsis has variable impact on neonatal glucose level leadingto hypoglycemia (blood sugar level 125 mg/dl).9,10 Septic neonates experiencehypoglycemia because of reluctance to feed, increased metabolicdemand, hypothermia and defective gluconeogenesis. Differentstudies have shown its variable association with brain injury,epilepsy and neurocognitive outcome in later childhood.11,12

    Whereas, hyperglycemia is due to increased production of stresshormone like glucagon, growth hormone, catecholamines,glucocorticoids and an increase in proinflammatorycytokines.12,16 Complications associated with neonatalhyperglycemia are intra-ventricular hemorrhage, late onsetinfections and necrotizing enterocolitis.13

    Incidence of altered blood glucose in septic neonates varies indifferent studies showing 7.63% to 13.5% of septic neonatesexperiencing hypoglycemia.14,15 While, 23.8%16 to 50%13 ofseptic neonates observed to have hyperglycemia. Reportedmortality in hypoglycemic septic neonates is 42.8%, whereasit is 11.8% to 32.4 % in septic neonates with hyperglycemia.15,18,19

    There is paucity of local data regarding impact of serum glucoselevels on outcome of septic babies. The current study wasdesigned with an aim to fill in this gap. The information obtainedwill help in identifying those septic babies that requirepreferential attention and channelizing resources and willultimately lead to improvement in their morbidity and mortality.

    Abstract

    BackgroundIn Pakistan, neonatal mortality rate is 42 per 1,000 live birthsand sepsis contributes up to 28% neonatal deaths.2,3,5 Sepsishas variable impact on neonatal glucose level. This study wasconducted to determine if abnormal glucose levels compromisethe outcome in neonatal sepsis.

    MethodsThis study was conducted in the Neonatology Department ofThe Children’s Hospital, Lahore from September 2017 toFebruary 2018. Two hundred and twenty septic neonates withpositive blood culture were included in this descriptive crosssectional study. Blood glucose estimation was done using bloodglucose strips, later confirmed with spectrophotometer technique.Statistical analysis was performed using SPSS v19.

    ResultsAmong 220 blood culture proven septic neonates, there were128 (58.2%) males and 92 (41.8%) females. There were 71(32.27%) low birth weight babies and 36 (16.4%) large forgestational age babies. Blood sugar level monitoring showedthat hypoglycemia and hyperglycemia was noted in 35(15.9%)and 52(23.63%) neonates, respectively, while 133 (60.5%) hadnormal glucose level. Among all neonates, 145 (65.9%) survivedwhile 75 (34.1%) expired. Among total 75 expiries,hypoglycemia, euglycemia and hyperglycemia were documentedin 12(16%), 39 (52%) and 24 (32%) babies, respectively.Hyperglycemic neonates had significantly increased mortality(p=0.036) and prolonged hospital stay (p=0.02).

    ConclusionAbnormal serum glucose level compromises the outcome inneonatal sepsis. Hyperglycemia leads to significant increase inmortality in neonatal sepsis and prolonged hospital stay.

    Key wordsabnormal serum glucose, neonatal sepsis, neonatal mortality.

    IntroductionNeonatal mortality is a major health issue globally and

    Corresponding Author: Muhammad Usman Khalid,Senior Registrar Neonatology,The Children’s Hospital & the Institute of Child Health,Lahore,Pakistan.Email: [email protected]

    Muhammad Usman Khalid, Farah Haroon, Sikandar Hayat, Rafia Gul, Khawaja Ahmad Irfan Waheed, Javaria Younus

    The Children’s Hospital & the Institute of Child Health, Lahore, Pakistan.

    Does Abnormal Serum Glucose Level Compromise the Outcome in Neonatal Sepsis?

  • 70 . Infectious Diseases Journal of Pakistan

    Material & MethodsThis descriptive cross sectional study was conducted fromSeptember 2017 to February 2018 in the Neonatology Unit ofThe Children’s Hospital & the Institute of Child Health, Lahore.It was initiated after obtaining permission from the InstitutionalReview Board of the hospital. Informed written consent wasobtained from parents or guardians. Sample size was calculatedwith 80% power of test and 5 % level of significance by usingformula:

    n=Z^2(p) (1-p)/d^2

    Blood glucose estimation of every neonates with probablesepsis was performed at the time of admission by glucose teststrips (hexokinase method) later confirmed withspectrophotometer technique. Neonates with blood cultureproven sepsis were included in study and neonates with surgicalproblems, malformations, syndromes, infant of diabetic motherand those who received intravenous glucose within 6 hoursbefore or after admission before checking of glucose level wereexcluded. Incomplete data and left against medical advice(LAMA) before completion of data were also excluded.

    Each septic neonate was managed as per standard institutionalguidelines. On the basis of blood sugar, babies were classifiedinto groups as hypoglycemia (blood sugar level 125 mg/dl).9,10 Information including demographic data,outcome and duration of hospital stay were recorded on dataform. Duration of stay more than 14days was labeled asprolonged hospital stay.

    Statistical analysis was performed using Statistical Package forSocial Sciences (SPSS) 19. The studied variables were describedby numbers and percentages. Chi-square test was applied tostudy differences in the various categories and group. P-value3.5 12(33.33%) 19(52.77%) 05(13.88%) 36(16.36%)

    Total 35(15.90%) 133(60.45%) 52(23.63%) 220 (100%)

  • Volume 28 Issue 04 Oct - Dec 2019. 71

    euglycemic neonates, 39(29.3%) died while 94(70.7%) survivedwith (p value =0.06). Among 52 hyperglycemic neonates,24(46.1%) died while 28(53.9%) survived (p-value = 0.036)(figure 1).

    Among 35 hypoglycemic neonates, 14(40%) had prolongedhospital stay ( p=0.31) and in euglycemic neonates, 59(44.36%)

    had prolonged hospital stay (p=0.21). Among 52 hyperglycemicneonates, 32(61.5%) had prolonged hospital stay (p=0.023)(figure 2).

    DiscussionNeonatal sepsis is one of the major contributing factors amongthe numerous risk factors for neonatal morbidity and mortality.

    Fig 1. Outcome of septic neonates in relation to blood glucose level

    Fig 2. Length Hospital stay

    Abnormal glucose metabolism in neonatal sepsis may worsenthe outcome in neonates. This descriptive cross sectional studywas carried out with an objective to find the effect of bloodglucose level on outcome in confirmed neonatal sepsis.

    In our study, males were 1.4 times more as compared to femaleneonates. Similar demographic patterns were observed in studies

    carried out in various NICUs.13,16 Low birth weight is animportant risk factor for neonatal sepsis.20 Septic low birthweight babies are more prone to have altered blood glucoselevel because of intricate multifaceted mechanism involvingaltered endogenous glucose production, insulin response,catecholamine and their antagonists along with reduced oralintake and hypothermia.13 Sultan11 has shown in study that15.3% septic low birth weight neonates have hypoglycemia.Similarly in our study, 19.71 % septic low birth weight neonateswere hypoglycemic. On the other hand, fifty percent of theseptic low birth weight babies experienced hyperglycemia.Whereas, reported incidences of hyperglycemia in VLBWbabies vary a lot between 20 and 80% due to different cut offvalues used to define hyperglycemia in different studies.21

    In a study conducted by Swain15 7.63% of all septic neonateshad hypoglycemia while in a study from Bangladesh,14

    documented prevalence of hypoglycemia was 13.5% in neonatalsepsis. Studies by Sabzehei et al16, Islam17 and Gul13 reportedthat 29%, 23.8%, and 50% of all septic neonates hadhyperglycemia, respectively. In our study 15% septic neonates

  • 72 . Infectious Diseases Journal of Pakistan

    were hypoglycemic, 23.6% hyperglycemic and 61.4%euglycemic. The difference in results is because of differencein study design, including birth weight and different levels tobe considered as hyperglycemia or hypoglycemia.

    Reported mortality in hypoglycemic neonates with probablesepsis is 32%, by Ahmed and Khalid.11 The results arecomparable to our study as 34.3% hypoglycemic septic neonatesdied. This similarity could be due to similarity in studypopulation. In a study from Thailand and Sudan, 32.4% and11.8% of septic neonates with hyperglycemia died.18,19 However,reported mortality was quite high (46.1%) in our septichyperglycemic neonates. This difference can be due to differentcomorbidities with hyperglycemia leading to high mortality.

    Prolonged hospital stay was observed in hyperglycemic neonateswhich is attributed to complications related to high bloodglucose level requiring interventions including intraventricularhemorrhage and necrotizing enterocolitis.. Sabzehei et al22

    found that hyperglycemic neonates had prolonged hospital stayas compared to non-hyperglycemic neonates. This is comparableto our study where prolonged hospital stay was statisticallysignificant in hyperglycemic septic neonates.

    For the babies with confirmed neonatal sepsis, there must bea meticulous monitoring of glucose level as they are at risk ofdeveloping hyperglycemia which, if managed early may leadto better outcome otherwise lead to an adverse outcome andprolonged hospital stay. Further, research work needed by thetorch bearers in neonatology field to make a consensus statementregarding the target blood glucose levels in neonatal sepsis toimprove the outcome.

    ConclusionAbnormal serum glucose level compromises the outcome inneonatal sepsis. Hyperglycemia leads to significant increase inmortality in neonatal sepsis and prolonged hospital stay.

    References1. World Health Organization. (2017). Neonatal mortality. [online] Available

    at: http://www.who.int/gho/child_health/mortality/neonatal/en/ [Accessed4 Oct. 2017].

    2. National Institute of Population Studies (NIPS) [Pakistan] and ICF. 2018.Pakistan Demographic and Health Survey 2017-18. Islamabad, Pakistan,and Rockville, Maryland, USA: NIPS and ICF.

    3. Committing to Child Survival: A Promise Renewed – Progress Report

    2015 [Internet]. UNICEF. 2015 [cited 21 October 2017]. Available from:h t t p s : / /www.un i ce f . o rg /pub l i c a t i ons / i ndex_83078 .h tml .

    4. World Health Organization. World Health Statistics 2015.www.who.int/gho/publications/world_health_statistics/2015/en/.

    5. Khan A, Kinney M, Hazir T, Hafeez A, Wall S, Ali N et al. Newbornsurvival in Pakistan: a decade of change and future implications. HealthPolicy and Planning. 2012; 27(suppl_3):iii72-iii87.

    6. Javaid S, Waheed K, Sheikh M, Gul R, Nizami N. Is ThrombocytopeniaConsistent with Specific Bacterial/Fungal Neonatal Sepsis?. Infec Dis JPak 2016; 25(2):27-30.

    7. Bentlin M, de Souza Rugolo L. Late-onset Sepsis: Epidemiology,Evaluation, and Outcome. Neo Reviews 2010; 11(8):e426-e435.

    8. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectiousdiseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013;60:367–89.

    9. Harris D, Weston P, Harding J. Incidence of Neonatal Hypoglycemia inBabies Identified as at Risk. The J Pediatr 2012; 161(5):787-791.

    10. Jain V, Chen M, Menon K. Disorders of carbohydrate metabolism. GleasonC A, Devaskar S U. Avery’s Diseases of the Newborn. 9th Ed: USA;Saunders 2012; 1327-9.

    11. Ahmad S, Khalid R. Blood Glucose Levels in Neonatal Sepsis andProbable Sepsis and its Association with Mortality. 2012 Jan; 22(1):15-18.

    12. Branco RG, Tasker RC, Garcia PCR, Piva JP, Xavier LD. GlycemicControl and Insulin Therapy in Sepsis and Critical Illness. Jornal dePediatria 2007; 83: 128-36.

    13. Gul R, Waheed KAI, Sheikh M, Javaid S, Haroon F, Fatima ST. Ishyperglycemia a risk factor for neonatal morbidity and mortality? PakArmed Forces Med J 2017; 67 (4): 621-26

    14. Islam Z, et al. Evaluation of hypoglycemic status and causative factorsin neonatal sepsis. Int J Contemp Pediatr 2017 Nov; 4(6):1927-1933.

    15. Swain A, Das K , Tripathy SK , Behera S, Satpath SK. Study of morbiditypattern of hypoglycemia in neonates admitted to a tertiary care centeran experience of two years. ejpmr 2017; 4(7):497-502.

    16. Islam MF, Mia MAH, Akhter KR, Haque M, Malik M. Glycemic Statusand its Effect in Neonatal Sepsis in a Tertiary Care Hospital. BangladeshJ Child Health 2016; 40(1):21.

    17. Sabzehei M K, Afjeh S A, Shakiba M, Alizadeh P, Shamshiri AR, EsmailiF. Hyperglycemia in VLBW Infants; Incidence, Risk Factors and Outcome.Arch Iran Med 2014; 17(6): 429-34.

    18. Tareen Z, Jirapradittha J, Sirivichayakul C, Chokejindachai W. FactorsAssociated with Mortality Outcomes in Neonatal Septicemia in SrinagarindHospital, Thailand. Neonat Pediatr Med 2017; 3:131. doi:10.4172/25724983.1000131.

    19. Mohammed MMM, Abdel Rahman SMK. Frequency of neonatalhyperglycaemia at Gaafar Ibnauf Children’s Hospital: Clinical aspectsand short term outcome. Sudan J Paediatr 2016; 16 (1):45 - 52.

    20. Schrag SJ, et al. Risk factors for neonatal sepsis and perinatal deathamong infants enrolled in the prevention of perinatal sepsis trial, Soweto,South Africa. 2012 Aug; 31(8):821-6.

    21. Decaro M, Vain N. Hyperglycaemia in preterm neonates: What to know,what to do. Early Human Development. 2011; 87:S19-S22.

    22. Sabzehei M K, Afjeh S A, Shakiba M, Alizadeh P, Shamshiri AR, EsmailiF. Hyperglycemia in VLBW Infants; Incidence, Risk Factors and Outcome.Arch Iran Med 2014; 17(6): 429-34.

  • Volume 28 Issue 04 Oct - Dec 2019. 73

    ORIGINAL ARTICLE

    Corresponding Author: Naureen Omar,Assistant Professor,Department of Community Health SciencesFatima Memorial College of Medicine and Dentistry,Lahore, Pakistan.Email: [email protected]

    Socioeconomic Status of Father and Vaccination Status of Children: A Community Based HouseholdSurvey

    Naureen Omar*, Shamaila Hassnain*, Umbreen Navied*, Iram Manzoor**

    *Department of Community Health Sciences, Fatima Memorial College of Medicine and Dentistry,Lahore, Pakistan

    ** Department of Community Health Sciences, Akhtar Saeed Medical College. Lahore, Pakistan

    Abstract

    BackgroundPakistan, being a developing country faces the challenge ofcompromised maternal and child health, as a state it is laggingbehind with poor child health status and extremely high mortalityrates for the past many years. Immunization can be consideredto be the keystone factor to help combat with this situation.

    ObjectiveTo assess the influence of fathers’ socioeconomic status on thevaccination status of children aged less than five years in theNorthern Peri-Urban areas of Lahore.

    DesignCommunity based household survey

    MethodologyCommunity based household survey was conducted in NorthernPeri-urban areas of Lahore within a period of three months. Atotal of 939 households were visited, married couples havingat least one child were enrolled in the study after informedconsent. A pretested structured questionnaire translated in locallanguage was used to collect data pertaining to socio-demographic profile, paternal education, occupational statusand immunization status of under five children.

    ResultSurvey was conducted on a total of 939 households inhabitedby 5,356 members,836 household had male heads, mean age45+14 years and 153 were headed by females, mean age 52+15years. Children under 5 years of age, 617 (74%) were fullyvaccinated, 111 (13%) partially vaccinated and 108 (13%)unvaccinated. Income of 541 (65%) was less than 15,000 and295 (35%) more than 15,000. Majority fathers were uneducatedor had attended madrasah/Quran literate 550 (66%). Nosignificant relationships were exhibited between vaccinationstatus of children, income and father’s educational status

    ConclusionAs observed father’s educational status was pertinent indetermining the vaccination status of their children in additionto the socioeconomic status. Majority fathers were illiteratethus highlighting the need of educational services in additionto better EPI coverage within this particular area.

    KeywordsImmunization, Father Education, Household Survey

    IntroductionPakistan, being a developing country faces the challenge ofcompromised maternal and child health, as a state it is laggingbehind with poor child health status and extremely high mortalityrates for the past many years. In 2017 the under –five mortalitieshave been reported to be 74.9/ 1000 live births.1 Appropriate,acceptable and implementable steps need to be taken to identify,improve and reduce the factors responsible for thesecircumstances. Immunization can be considered to be thekeystone factor to help combat with this situation.2

    The Expanded Program on Immunization was launched in 1979by UNICEF and WHO, with the objective of prevention ofchildhood diseases. This program still faces a number of hurdlesin provision of complete immunization. According to thePakistan Demographic and Health Survey 2017-2018 80% ofchildren are fully vaccinated in Punjab and only 1% are notvaccinated.3 Punjab Health Survey (PDHS) 2016 over 81% ofchildren aged 12-23 months are fully vaccinated in Punjab.3

    According to the Pakistan Demographic Health Survey (PDHS)2017-2018 the total vaccination coverage in Pakistan hasimproved from 54% to 66%.3

    Education inculcates moral and ethical values, positive thinkingand attitudes within an individual. Education helps to strengthenone’s mind enabling to perceive to deal with specific challengesin life. Parental education plays a significant role in decisionmaking and comprehending different preventive health servicesconcerned with their children, especially immunization. Manystudies, emphasize and support that educated parents play adominant role in regards to immunization of their children. Thecomprehensive involvement of both parents is fruitful.4,5 It was

  • 74 . Infectious Diseases Journal of Pakistan

    observed that lowest immunization coverage was noticed inchildren with lesser educated fathers, thus parental educationhad a positive effect in promoting immunization coverage.6

    Gaps have been identified in the knowledge of parents regardingprevention of infectious diseases thus highlighting the importanceof awareness of parents especially fathers regarding relevantinformation related to these diseases.7 It has been noted that theavailability of relevant information with respect to children’shealth is important for parents as it influences them in decisionmaking, especially in relation to immunization.8 Anothermisleading factor responsible for prevention of immunizationare the associated risks which may occur due to immunization.Misconceptions regarding immunizations need to be reviewedto reduce chances of non-immunization.9 It has been distinguishedthat the immunization status of children is related to the socio-economic status of the household. In India it has been observedthat children belonging to the poorest economic householdshowed an increase trend in non-immunization.10 Low andmiddle income countries also exhibit missed opportunities inimmunization.11 Studies reported different issues responsiblefor low immunization coverage in Pakistan. Researches inPakistan have also highlighted different issues responsible forthe low vaccination coverage.

    These included distant vaccination centers, improper knowledgeof Expanded Program on Immunization (EPI) schedule andparental education.12

    It is imperative that we understand the relationship of parentalespecially father’s education and socioeconomic status indeciding the vaccination status of their children. The parent’sawareness especially fathers in relation to the understandingof the significance of vaccination requires interventions toaddress this domain, as decision making of children’s healthis dependent on the parents. Pakistan is in dire need to improveits EPI vaccination coverage to overcome and eliminate theprevailing communicable diseases in children. Research targetingthis domain is essential as it would help us identify areas wherewe could use interventions to enhance the awareness of parentsespecially fathers regarding the importance of vaccination asthey play a major role in decision making. In addition, Pakistanis in dire need to improve its EPI vaccination coverage so asto target the elimination of targeted communicable diseases.

    This study was conducted with the aim to assess the influenceof father’s socioeconomic status on the immunization status ofchildren aged less than five years in the Northern Peri Urbanareas of Lahore. This study was conducted with the aim toassess the influence of father’s socioeconomic status on thevaccination status of children aged less than five years in theNorthern Peri Urban areas of Lahore.

    MethodologyIn the Northern Peri urban areas of Lahore including the townsof Malikpur, Bheni, Talwara, Jandiala, Icho Gill and Awan Dhai

    Wala, Union Council 176 a community based household surveywas conducted within a period of three months. Each townapproximately has 2500 households, every 15th house (calculatedby systematic random sampling/kth fraction) was visitedamounting to a total of 939 households. Married couples havingat least one child were enrolled in the study after informedconsent. Investigators conducted personal interviews collectingdata pertaining to socio-demographic profile, paternaleducational, occupational status and EPI vaccination status ofunder five children. Children up to five years of age receivingcomplete course of EPI vaccination were considered fullyvaccinated, unvaccinated were children up to five years of agereceiving no dose of any EPI vaccination and partially vaccinatedwere children up to five years of age missing even one dose ofany EPI vaccination. A non-response rate of less than 3% wasencountered. A pretested structured questionnaire translated inlocal language was used. Pilot study was conducted on tenhouseholds before using the instrument. Consent was takenfrom all of the participants and Institutional Review Boardclearance was sought before collection of data. Analysis wasdone on SPSS version 20 with chi square being the test ofsignificance at 95% confidence interval p value of 0.05 hasbeen considered significant. Chi Square was calculated.

    ResultsThis survey was conducted on a total of 939 households inhabitedby 5,356 members, out of whom 836 household had male heads,mean age 45.5+ 14.6 years and 153 were headed by females,mean age 52.6+ 14.9 years.

    Households with male heads were evaluated for further results.Children under 5 years of age, 617 (74%) were fully vaccinated,111 (13%) partially vaccinated and 108 (13%) unvaccinated.The questionnaire was based on categories of income definedon the basis of previous surveys done in the community ofNainsukh. So, the mean income cannot be generated. The crosstabulation between the education of fathers and vaccinationstatus shows that there was no significant relationship betweeneducation status and vaccination based on our results. Therelationship of income with vaccination status exhibited a non-significant relationship with a p value of 0.060, indicating thathouseholds with income more than 15,000 rupees had only 6%more vaccination coverage than households with low income.

    DiscussionDespite many strategies Pakistan faces the dilemma of lowvaccination coverage of children which can be attributed tomany factors. It is utmost importance that these factors behighlighted. This study was conducted to highlight the influenceof father’s socioeconomic status on the vaccination status oftheir children. Majority children of the Northern Peri urbanareas of Lahore were vaccinated as witnessed in the currentstudy depicting the overall picture of Punjab especially Lahore.More than half of the children were fully vaccinated supportingthe fact that majority parents were aware of the importance of

  • Volume 28 Issue 04 Oct - Dec 2019. 75

    vaccination in addition to proper coverage of all areas withinthe province.13

    Various studies support the fact that maternal education isessential for the well-being of children, but on the other handfather’s education cannot be denied as being head of thehouseholds they are the decision makers.14, 15, 16 Analysis of sixlow income countries including Pakistan reported that countrieswith low paternal educational status had less vaccinationcoverage.17 In a Nigerian study similar results were reportedin addition lack of approval of father towards vaccination, poorpaternal educational and socioeconomic statue were emphasizedupon.18 Contrarily in the current study although majority fatherswere illiterate or had a low educational status the vaccination

    Cross Tab I: Relationship between Educational Status ofFather and Vaccination Status

    Children Vaccination Status(n = 836)

    Educational Status Yes No

    Illiterate/ Quran /Madrassah 459 91

    (83.5%) (16.5%)

    Primary to Matric 206 34(85.9%) (14.1%)

    Intermediate 31 3(91.2%) (8.8%)

    Bachelor & Above 12 0(100%) (0%)

    Total 708 128(84.7%) (15.3%) p=0.38

    Cross Tab II. Relationship between Income and VaccinationStatus

    Children Vaccination Status(n = 836)

    Income /months Yes No Total(household)

    Less than 15,000 447 94(82.6%) (17.3%)

    More than 15,000 261 34(88.4%) (11.6%)

    Total 708 128(84.7%) (15.3%) p=0.06

    Table 1: Socio-demographic data

    Frequency (%)

    Income/monthLess than 15,000 541 (65%)More than 15,000 295 (35%)

    Educational status of FatherIlliterate/Quran/Madrasah 550 (68%)Primary to Matric 240 (29%)Intermediate 34 (4%)Bachelors & above 12 (1%)

    Immunization Status of Last Born ChildPartially vaccinated 111 (13%)Unvaccinated 108 (13%)Fully Vaccinated 617 (74%)

    Total 37,560 Households Enrolled

    Less than 3%Non-response rate

    After systematicrandom samplingevery 15th house

    was visited

    836 Householdshad male heads

    153 Householdshad female heads

    Total 939Households

    assessed

    36,621 Householdsagreed for survey

    Flow Diagram:

    The reasons for non-response rate among the households were:1. Not willing to be a part of the study.2. Non-availability of the household members on the particular

    day of pre-survey.

  • 76 . Infectious Diseases Journal of Pakistan

    coverage was high and a significant relationship was notestablished (p value 0.382). This can be attributed to the factthat this study was conducted in a Peri urban area whereawareness levels were high as vaccination camps were beingconducted in addition during surveys importance of EPIvaccination was being emphasized upon parents as was doneduring our data collection too.

    The current study witnessed most of the households to have anincome of less than 15,000 PKR in accordance with theeducational status of fathers and low vaccination status of theirchildren (p value 0.008), as was observed in a study conductedin Africa majority households belonged to the lower class withnon- educated father’s thus less vaccinated children.19

    A study conducted in Sindh, Pakistan highlighted that poorsocioeconomic status of parents can be considered to be animportant predictor of the vaccination status of their childrenmajority having a monthly income of less than 3000 PKR.20,21

    The irony being that free vaccination programs are not the onlysolution for adequate vaccination we need to take into accountmany factors.

    This study emphasizes on the fact that we still need to investigateand identify various factors associated with immunization statusof children. Limitations encountered were minimal sample sizewas enrolled in lieu of the feasibility. Vaccination evidence wasbased on responses as in most of the houses vaccination cardswere not available so the element of recall bias cannot be denied,but data was collected under the supervision of the principalinvestigator after training of the data collectors.

    ConclusionVaccination coverage in the Northern Peri Urban areas ofLahore is 85%. As observed father’s educational status wasa pertinent in determining the immunization status of theirchildren in addition to the socioeconomic status. Majorityfathers were illiterate thus highlighting the need of educationalservices in addition to better EPI coverage within this particulararea. Surveys in different geographical areas need to beconducted so as to have a broader overview of the vaccinationcoverage, status and factors associated with it throughout thecountry.

    AcknowledgementsThe authors are thankful to the Department of CommunityHealth Sciences, FMHCM&D and students of 4th year MBBSfor their contribution in the data collection. Worth mentioningare the contributions of Mr Tipu Sultan in the analysis of thedata. We would like to thank the people of the communities wevisited.

    References1. Unicef: Under Five Mortality. Sept 2019 https://data.

    unicef.org/topic/child-survival/under-five-mortality/ Cited

    25 August 2017.2. Shoukat M, Khurmi MS, Faheem MU. Child Health Status

    in Pakistan. Student JAMC. 2015; Sep 15:1(1).3. PDHS – 2017-18 Key indicator report Aug 2018.

    http://www.nips.org.pk/abstract_files/PDHS. Cited 25August 2017

    4. Brugha RF, Kevany JP, Swan AV. An investigation of therole of fathers in immunization uptake. Int J Epidemiol1996;25(4):840-5.

    5. Garfield CF, Isacco A. Fathers and the well-child visit.Pediatrics 2006;117(4):637-45.

    6. Rammohan A, Awofeso N, Fernandez RC. Paternaleducation status significantly influences infants’ measlesvaccination uptake, independent of maternal educationstatus. BMC public health 2012;12(1):336.

    7. Hilton S, Hunt K, Petticrew M. Gaps in parentalunderstandings and experiences of vaccine-preventablediseases: a qualitative study. Child Care HLTH DEV 2007;33(2):170-9.

    8. Sporton RK, Francis SA. Choosing not to immunize: areparents making informed decisions? Fam Pract2001;18(2):181-8.

    9. Raithatha N, Holland R, Gerrard S, Harvey I. A qualitativeinvestigation of vaccine risk perception amongst parentswho immunize their children: a matter of public healthconcern. J Public Health 2003;25(2):161-4.

    10. Devasenapathy N, Jerath SG, Sharma S, Allen E, ShankarAH, Zodpey S. Determinants of childhood immunisationcoverage in urban poor settlements of Delhi, India: a cross-sectional study. BMJ open 2016;6(8):013015.

    11. Sridhar S, Maleq N, Guillermet E, Colombini A, GessnerBD. A systematic literature review of missed opportunitiesfor immunization in low-and middle-income countries.Vaccine 2014;32(51):6870-9.

    12. Siddiqi N, Khan A, Nisar N, Siddiqi AE. Assessment ofEPI (expanded program of immunization) vaccine coveragein a peri-urban area. JPMA 2007;57(8):391-5.

    13. Shaheen A, Batool S, Mahmood MA. Coverage ofImmunization among Poor Children. PJMHS 2012;(1):195-197

    14. Babatsikou F, Vorou R, Vardaki Z, Galani S, Ktenas E,Koutis C. Childhood vaccination uptake and factors affectingthis in Athens, Greece. Health Sci J 2010;4(4):237.

    15. Aslam M, Kingdon GG. Parental education and childhealth—understanding the pathways of impact in Pakistan.World Dev 2012;40(10):2014-32.

    16. Cochrane SH, Leslie J, O'Hara DJ. Parental education andchild health: intracountry evidence. Health Policy Educ1982;2(3-4):213-50.

    17. Ilah B, Sakajiki A, Musa A, Edem B, Adelakun M, AdenijiA, Kaura N. Immunization and socioeconomic status ofchildren 12-59 months attending a specialist hospital,Gusau, Nigeria. ATMPH 2015;8(2):23.

    18. Al-lela OQ, Bahari MB, Salih MR, Al-abbassi MG, ElkalmiRM, Jamshed SQ. Factors underlying inadequate parents’

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    awareness regarding pediatrics immunization: findings ofcross-sectional study in Mosul-Iraq. BMC Pediatrics2014;14(1):29.

    19. Sanou A, Simboro S, Kouyaté B, Dugas M, Graham J,Bibeau G. Assessment of factors associated with completeimmunization coverage in children aged 12-23 months: across-sectional study in Nouna district, Burkina Faso. BMCInt health human rights 2009;9(1):S10.

    20. Shaikh S, Taj TM, Kazi A, Ahmed J, Fatmi Z. Coverageand predictors of vaccination among children of 1–4 yearsof age in a rural sub-district of Sindh. JCPSP 2010;20(12):806-10.

    21. Tikmani SS, Soomro T, Ali SA. Vaccination Status andFactors for Non-Vaccination in Children at a Tertiary CareHospital. Int J Vacc Res 2017;2(1):1.

  • ORIGINAL ARTICLE

    78 . Infectious Diseases Journal of Pakistan

    Emergence of Multidrug Resistant Gram-negative Pathogens in an Intensive Care Unit of a TertiaryCare Hospital

    Zehra NM, Hanif F, Khursheed U, Jaffer SR, Yousuf S, Nadeem S

    PNS Shifa Hospital, Karachi, Pakistan

    Correspondence Author: Nadia Midhat Zehra,Resident Microbiology, Department of Pathology,PNS Shifa Hospital, Karachi, PakistanEmail: [email protected]

    Abstract

    ObjectivesTo determine the antimicrobial resistance pattern amongpathogenic gram-negative bacilli isolated from patients withnosocomial infections at PNS Shifa hospital, Karachi.

    Study designDescriptive cross sectional study

    Place and Duration of studyThe study was carried out at the Department of Microbiology,PNS Shifa hospital from Jan 2015 - Dec 2016.

    MethodologyAll samples received from surgical and medical intensive careunit were included in the study. Samples from patients withinsufficient medical history were excluded. Initially, gram stainfrom fresh sample was made followed by inoculation on Bloodagar, Mac Conkey agar and Chocolate media (Biomeurx) for24-48 hours. Pus samples were inoculated additionally onanaerobic media, as per CLSI 2016 guidelines. Positive cultureswere tested for antimicrobial susceptibilities by Kirby-Bauertechnique according to CLSI guidelines. The results were furtherconfirmed by minimum inhibitory concentration.

    ResultsIn 900 patients, a total of 248 gram negative bacilli were isolatedin either mono-microbial or poly-microbial cultures. The mostfrequent pathogens were Klebsiella pnemoniae 88( 32%)followed by Acinetobacter baumanii 63 (23%), Pseudomonasaeruginosa 36 (14%), and E.coli 31(11%), and less frequentlyisolated organisms, Enterobacter aerogenes , Enterobactercloacae and Stenotrophomonas maltophilia , Salmonella typhi,Proteus mirabilis, Proteus vulgaris, Citrobacter freundii,Burkhorderia cepacia ,Serratia marcesens and Serratia odoriferacomprises 12% of the isolates. The tested antimicrobials wereampicillin, amoxicillin-clavulanate, ceftriaxone, cefepime,ceftazidime, doxycycline, Co-trimoxazole, gentamicin, amikacin,ciprofloxacin, levofloxacin, tazobactum-piperacillin, imipenem,meropenem and, polymyxin. The antimicrobial susceptibility

    was high for polymyxin (100%), imipenem (44.6%), meropenem(44.5%), sulbactam-cefoperazone (42.75%) tazobactum-piperacillin (40%), amikacin (29%), gentamicin (31%),doxycycline (28%), ciprofloxacin (12%). Carbapenem resistancewas highest amongst Pseudomonas aeruginosa , Klebsiellapnemoniae. and Acinetobacter baumanii (76%), followed by,and Enterobacter aerogenes (69%) E.coli (30%). All carbapenemresistant isolates were tested for susceptibility topolymyxin, susceptibility to which was 100%.

    ConclusionAntimicrobial susceptibility of the three most common isolatesin our study has been restricted to carbapenems and colistin.Even carbapenem resistance is significantly higher, that makesit unsuitable to be used as an empirical antibiotic. The decreasingsensitivity of MDR gram negative bacteria to third generationcephalosporins and carbapenems leaves us with colistin as theonly option.

    Use of colistin has become a unlikeable necessity in spite ofthe cost and side effects pose by them.

    Key WordsAntibiotic, Antimicrobial resistance, Gram-negative Isolates,Intensive care unit

    IntroductionGram negative bacilli causing significant numbers of infectionsin intensive care units (ICU)1 are a great threat as most of themexist as multidrug resistant isolates.

    They are responsible for 45–70% of ventilator-associatedpneumonia (VAP), 20–30% of catheter-related bloodstreaminfections and generally are involved in ICU-acquired sepsissuch as surgical site or urinary tract infections (UTI).2

    Nevertheless, alarming resistance rates are now beingincreasingly reported worldwide, and rising trends may elicitconcerns for the coming years.3

    Exclusively restricted to the hospital setting, this issueincreasingly applies for patients with healthcare-associated.4,5

    and even community-acquired infections.6 Patients are usuallyfound to be on prolonged exposure to broad spectrum antibiotics,invasive procedures and suffer from an immunocompromisedstatus.7 Enterobacteriaceae and non-fermenting GNB

  • Volume 28 Issue 04 Oct - Dec 2019. 79

    (Pseudomonas aeruginosa, Acinetobacter baumannii andStenotrophomonas maltophilia) account for the major part ofthe troublesome situation.8

    A high prevalence of extended spectrum beta lactamaseproducing E.coli and Klebsiella pnemoniae has been reportedmany times in blood stream infections. 9, 10

    A hoard of antibiotic-inactivating enzymes and non-enzymaticmechanisms have contributed to antimicrobial resistance ingram negative bacteria (GNB).11 Both may be intrinsicallyexpressed by a given species of bacteria (chromosomal genes),or acquired by a subset of strains within the same specie as aconsequence of mutations in chromosomal genes or horizontaltransfer mechanisms incorporated in mobile genetic elements.2

    The reasons for development of resistance are multiple and areattributed to antibiotic overuse and misuse together with failinginfection control practices in health care setting.12

    Multidrug resistant gram-negative infections are beingincreasingly reported from our critical care unit. In order toguide a clinicians in reforming a better treatment plan formultidrug resistant gram negative infections, we haveinvestigated the antimicrobial resistance patterns among gram- negative bacteria isolated from ICU patients at PNS Shifahospital Karachi and devise a plan to curb antibiotic resistance.

    Material & MethodsThis study was carried out at PNS Shifa hospital in Karachifrom January 2014 to December 2016. The study protocol wasapproved by Ethical Review Committee of PNS Shifa hospital.This was descriptive cross-sectional study. Sampling was doneby non-probability consecutive sampling technique.

    Patients belonging to adult ICU, pediatric ICU and neonatalICU were included in the study.Out of 900 culture positive specimens, 248 specimens that yieldnon-lactose fermenting and lactose fermenting gram negativerods were included in our study. The remaining 652 specimenscomprising of gram positive pathogens and fungal isolates wereexcluded from our study.

    Three sets of samples were taken in the ICU. First set consistedof diagnostic samples that were taken at the time of ICUadmission. These samples were not included in our study. Theremaining two sets were surveillance samples that were takenweekly and then followed twice weekly in order to monitorhospital acquired infections and identify carrier state of thepatient. Surveillance samples were included in our study.

    Specimens received for culture and sensitivity comprised ofBlood, Bronchi alveolar lavage, tracheal aspirates, sputum,body fluids, pus specimens, central venous catheter tips andurine specimens. Specimens were then inoculated on bloodagar, MacConkey agar and chocolate agar (Biomeurx) for 24-

    48 hours. Organism was identified up to species level usingAPI 20E and API 20NE.

    Sepsis in terms of microbiology was defined as one or morepositive blood culture collected during stay in the ICU. In anindividual patient, positive cultures from each site were countedas separate samples. All information was documented on aresearch questionnaire. The information collected includeddemographic characteristics of patients, site of infection, andantibiotic sensitivity of the isolate. MDR isolate was definedas resistance to 3 or more than three categories of antimicrobialagainst which it has been tested.13

    The isolates were identified using standard microbiologicaltechniques, on the basis of colony morphology and biochemicaltests using API 20E and 20NE (Biomeurx, France). Antimicrobialsusceptibility was determined by the Kirby-Bauer disc diffusionmethod on Muller-Hinton agar (Oxoid, UK). Antimicrobialdiscs used were: ampicillin amoxicillin –clavulanate, ceftriaxone,cefepime, ceftazidime, doxycycline, co-trimoxazole, gentamicin,amikacin, ciprofloxacin, levofloxacin, tazobactum-piperacillin,imipenem, meropenem, polymxin.

    The Muller-Hinton agar plates were incubated aerobically at35 ±2°C for 18-24 hours in ambient air. E. coli ATCC 25922was used for QC of discs. The interpretation of zone diameterswas done according to clinical and laboratory standards institute(CLSI) guidelines (2016). Isolates showing resistance toantimicrobial agents were confirmed by minimum inhibitoryconcentration using Etest method. The interpretation of minimuminhibitory concentration was done according to clinical andlaboratory standards institute (CLSI) guidelines (2016).14 Thedata was analyzed using SPSS 17.0. Descriptive statistics wereused to calculate frequencies and percentages of the qualitativevariables.

    As per definition, MDR organisms are those which showresistance to at least 3 different antibiotic groups.13 Antibioticsfor which susceptibility testing has been done and were foundto be susceptible to more than 80% isolates are included in thestudy. Multidrug resistant (MDR) has been defined for clinicallysignificant major gram negative bacteria such as Acinetobacterbaumanii, Pseudomonas aeruginosa, Escherichia coli, andKlebsiella pnemoniae. Antibiotics tested for gram negativepathogens were Aminoglycosides (AMG), Cephalosporins(CEPH), Carbapenems (CARB), Tetracyclines (TETRA) andFluroquinolones (FQ).

    Class 1: This class includes organism that pose resistance tofive classes of antimicrobials such as aminoglycosides, thirdgeneration cephalosporins, fluoroquinolones, carbapenems,and tetracyclines. Acinetobacter baumanii are labelled as class1 MDR organism as tetracyclines are tested only forAcinetobacter baumanii among MDR GNB.Class 2: Organism included in this class demonstrate resistance

  • 80 . Infectious Diseases Journal of Pakistan

    against four classes of antimicrobials such as aminoglycosides,third generation cephalosporins, fluoroquinolones andcarbapenems.Class 3: This class is further divided in 3a, 3b, 3c and 3d3(a): Resistance against three classes of antimicrobials such asaminoglycosides, third generation cephalosporins andfluoroquinolones but sensi t ive to carbapenems. 3(b): Resistance demonstrated against three classes ofantimicrobials such as third generation cephalosporins,fluoroquinolones and carbapenems but sensitive toaminoglycosides. 3(c): Resistant to three classes of antimicrobials such asaminoglycosides, fluoroquinolones and carbapenems, butsensitive to third generation cephalosporins. 3(d): Resistant to three classes of antimicrobials such asaminoglycosides, third generation cephalosporins andcarbapenems, but sensit ive to fluoroquinolones.

    Note: For general gram negative bacilli; ceftriaxone andceftazidime were used in third generation cephalosporins exceptfor Acinetobacter and Pseudomonas species, where onlyceftazidime was used. In category of carbapenems, meropenemwas used; aminoglycosides were represented by gentamicinand amikacin, and for fluoroquinolones, ciprofloxacin was themodel drug.

    ResultsAmong 900 culture positive patients selected for study, gramnegative rods were isolated from 248 (28%) patients.Most common clinical specimen yielding gram negativepathogens during the present study were respiratory specimens131 (47.9%) followed by blood 41 (15%) and pus 50 (18.3%).Distribution of pathogens among different clinical specimensreceived from the ICUs during the study period is shown in(table1). It was observed that Klebsiella pnemoniae 88 (32.2%)was the most common organism isolated from various clinicalspecimens in our study followed by Acinetobacter baumanii63(23%) (Figure1). Other common organisms isolated indecreasing order were Pseudomonas aeruginosa 36 and E.coli31 (12%).

    Frequency of pathogens in neonatal, pediatric and adult ICUs(table 2). Klebsiella pnemoniae N=11, Citrobacter species N=8and Enterobacter species N= 4 were recurrently reported fromthe pediatric ICUs. In Adult ICUs, Klebsiella pnemoniae, N=65Acinetobacter baumanii, N=60 and Pseudomonas aeruginosaN=33 were more common.

    The gram-negative bacilli in our study belong to familyEnterobacteracae and some isolates of non- enterobacteracaefamily. Antimicrobial resistance pattern is depicted in (table3). In our study we noted that Klebsiella pnemoniae of familyenterobacteracae ranks top in the gram negative bacilli isolatedfrom ICU. Most of the Klebsiella isolates were multi drugresistant organisms showing resistance against three or more

    than three groups of antimicrobials. High resistance was shownagainst carbapenems and aminoglycosides. Among non-enterobacteracae family, Acinetobacter baumanii andPseudomonas aeruginosa were most common clinical isolatesin this family. Both of these gram negative bacteria turned outto be, highly non-susceptible to quinolones, cephalosporinsand beta lactam inhibitor group of drugs. Resistance tocarbapenems was high and does not show any significantdifference when compared to isolates of enterobacteracae family.

    When we study co resistance pattern among significant gramnegative bacilli [tab-4], we find that out of 218 gram negativebacilli isolates recovered, 105(48.1%) isolates were multidrugresistant i.e., resistant to at least three or more than three classesof antimicrobial agents. About 14.6% of isolates are resistantto four groups of antimicrobials and 2.2% of isolates wereresistant to three classes of antimicrobial drugs. It was observedthat 34.09% of Klebsiella pnemoniae, 35% of Acinetobacterbaumanii and 38.8% of Pseudomonas aeruginosa showedcomplete resistance to aminoglycosides, quinolones, macrolides,tetracyclines and carbapenems.

    DiscussionAntimicrobial resistance among pathogens is a serious threatto mankind that is difficult to overcome. Multi-drug resistantinfections by gram negative bacilli are some of the key causesof deaths, morbidity and economic setback amongst hospitalizedpatients. Through this study we identify major organisms andtheir antimicrobial resistance patterns. We tend to find out theshortage of antimicrobials that we will be facing in near future.

    Klebsiella pnemoniae (35.4%) was the most common organismisolated from our intensive care unit. Jamil et al., in aretrospective study conducted at a tertiary care hospital15 hasnarrated similar findings where Klebsiella pnemoniae was themost common infective agent isolated. In a study by Siddiquiet al, Acinetobacter species was often isolated infective agentfollowed by Klebsiella pnemoniae.16 Different members of theenterobacteracae family isolated less often consists E.coli(12.5%), Enterobacter and Citrobacter species (4%). Thesemultidrug resistant isolates are a challenge to the treatingmedical practitioner and cause of economic burden for thehospital.

    Among members of non-enterobacteracae family, gram negativebacilli like Acinetobacter baummanii (25.4%) followed byPseudomonas aeruginosa (14.5%) were the ensuing commonclass of microorganisms isolated from clinical specimen. Theseisolates are reported from pus and respiratory specimens. Theyare next common to Klebsiella pnemoniae in their occurrencefrom respiratory specimens. All the three isolates havesignificantly different mechanisms which lead to theirp redominance in r e sp i r a to ry spec imens f romimmunocompromised patients of ICU. Klebsiella pnemoniae,have capsular antigens that resist complement mediated killing

  • Volume 28 Issue 04 Oct - Dec 2019. 81

    Table 1: Shows number of different clinical specimens received from ICU patients. Total specimens =273

    Blood(41) Respiratory Urine(32) Pus(50) Body fluids(10) CVP tip(9)15% specimens 11.7% 18.3% 3.6% 3.2%

    (131) 47.9%

    Acinetobacter Klebsiella E.coli(15) Klebsiella Klebsiella Klebsiellabaumanii (4) pnemoniae(59) 46.8% pnemoniae(6) pnemoniae(2) pnemoniae (4)9.7% 45% 12% 20% 44%

    Klebsiella Acinetobacter Klebsiella E.coli(3) Pseudomonas Enterobacterpnemoniae(14) baumanii(24) oxytoca(2) 6% aeruginosa (4) cloacae(1)34.1% 18.3% 6.2% 40% 11%

    Burkhorderia Pseudomonas Enterobacter Pseudomonas Acinetobacter Citrobactercepacia(1) aeruginosa(19) aerogenes(1) aeruginosa(5) baumanii(1) koseri(1)2.4% 14.5% 3.1% 10% 10% 11%

    Enterobacter E.coli(7) Citrobacter Acinetobacter Proteuscloacae(3) 5.3% freundii(1) baumanii(29) mirabilis(1)7.3% 3.1% 58% 10%

    Citrobacter Enterobacter Pseudomonas Proteuskoseri(2) aerogenes(1) aeruginosa(2) mirabilis(1)4.8% 0.76% 6.2% 2%

    Citrobacter Enterobacter Acinetobacter Citrobacterfreundii(4) cloacae(5) baumanii(5) freundii(1)9.7% 3.8% 15.6% 2%

    Pseudomonas Proteus Proteus Klebsiellaaeruginosa(5) mirabilis(1) mirabilis(1) oxytoca(1)12.1% 0.76% 3.1% 2%

    E.coli(6) Providencia Serratia14.6% rettgeri(1) odorifera(1)

    0.76% 2%

    S.typhi(1) Proteus2.4% vulgaris(1)

    0.76%

    Citrobacterkoseri(1)0.76%

    Citrobacterfreundii(1)0.76%

  • 82 . Infectious Diseases Journal of Pakistan

    whereas Acinetobacter baumanii and Pseudomonas aeruginosacolonize respiratory tract of patients on prolonged mechanicalventilation1 7 resulting in nosocomial infections.

    Antimicrobial resistance varies in two commonly occurringisolates of enterobacteracae family. Among, 34.9%(30/88) ofKlebsiella pnemoniae isolates were found to be resistant to 5categories of antimicrobials consisting of third generationcephalosporins, aminoglycosides, quinolones, carbapenemsand tetracyclines. Only 18.8 %( 16/88) of Klebsiella pnemoniaeisolates are found come underneath the class of 4MDR i.e.resistant to four categories of antimicrobials together with thirdgeneration cephalosporins, aminoglycosides, quinolones,carbapenems. As compared to Klebsiella isolates, a significantlyless degree of resistance is shown by E.coli. Among E.coli,only 6.45% (2/31) isolates are classified as five MDR i.e.resistant to cephalosporins, aminoglycosides, quinolones,carbapenems and tetracyclines and 3.22% (1/31) are classifiedas four MDR i.e. resistant to cephalosporins, aminoglycosides,quinolones, and Carbapenum.

    Members of non-enterobacteracae, show consistently higherresistance patterns against all major classes of antimicrobialsused in our study. This data is supported by Kaushal V Shethet al18 and Cai B et al.19 A 60 %(38/63) of Acinetobacterbaumanii were found to be resistant to be meropenem; whereas100 % (63/63) isolates are resistant to ceftriaxone .Resistanceis reduced to 57 % (36/63) once combinations(sulbactam/cefoperazone) were used. A 52% (34/63) isolatesdemonstrate resistance to amikacin and 60 % (38/63) isolatesare resistant to ciprofloxacin. Similar concordance patterns arementioned by Kaushal V Sheth at al.18 Only 36.5% (23/63)isolates of Acinetobacter baumanii are resistant to doxycycline.It can be assumed that doxycycline was found to be moreeffective against Acinetobacter baumanii compared to the otherantimicrobials, hence it can be a promising agent for thetreatment of Acinetobacter baumanii infections.

    Multidrug resistant Pseudomonas aeruginosa isolated frommultiple specimens of ICU patients is alarming, Resistance ofisolates of pseudomonas to class A category drugs includingceftazidime was found to be 72%(23/36), while 52.7 %(19/36)isolates showed resistance to cefoperazone/ sulbactam.Resistance to carbapenems and aminoglycosides was found tobe 69.4%(25/36) and 50%(18/36) respectively. Our isolatesrevealed 64% (23/36) resistance to ciprofloxacin. These resultsare in agreement with many alternative studies.20

    On comparison of co-resistance among multidrug resistantgram-negative bacilli, we discover lactose- non fermentinggram-negative bacilli superseding lactose -fermenting gramnegative isolates. It is evident that 30/88 (34.09%) Klebsiellapnemoniae isolates have ceased responding to five majorcategories of antimicrobials i .e. Cephalosporins,aminoglycosides, quinolones, carbapenem and tetracyclines.

    Fig 1. Pattern of gram negative Bacteria in percentages

    Table 2: Distribution of pathogens in neonatal, pediatricand adult Intensive care unit

    Neonatal ICU Pediatric ICU Adult ICU

    Klebsiella Klebsiella Klebsiellapnemoniae pnemoniae pnemoniaeN=12 N=11 N=65

    Enterobacter Citrobacter E.colicloacae freundii N=28N=4 N=8

    E.coli Citrobacter AcinetobacterN=1 koseri baumanii

    N=3 N=60

    Pseudomonas Pseudomonasaeruginosa aeruginosaN=3 N=33

    Acinetobacter Enterobacterbaumanii cloacaeN=3 N=6

    E.coli EnterobacterN=2 aerogenes

    N=1

    Serratia Burkhorderiaodorifera cepaciaN=1 N=1

    Salmonella typhi Proteus mirabilisN=1 N=4

    Providencia rettgeriN=1

    Proteus vulgarisN=1

  • Volume 28 Issue 04 Oct - Dec 2019. 83

    Table 3. Antimicrobial resistance pattern of gram negative isolates. % indicates resistance pattern of a clinical isolate tocorresponding antimicrobial agent

    Antimicrobial Klebsiella Acinetobacter Pseudomonas E.coli Other gramagent pnemoniae baumanii aeruginosa (N=31) negative rods

    (N=88) (N=63) (N=36) N=30

    Ceftriaxone/ 81 (92%) 63 (100%) 23 (72%) 29 (93.5%) 30 (100%)Ceftazidime

    Sulbactam- 66 (75%) 36 (57%) 19 (52.7%) 11 (35.4%) 14 (46.6%)Cefoperazone

    Meropenem 53 (60.2%) 38 (60%) 25 (69.4%) 6 (19.3%) 14 (46.6%)

    Gentamicin 69 (78.4%) 35 (55%) 21 (58.3%) 18 (58%) 17(56.6%)

    Amikacin 66 (75%) 34 (52%) 18 (50%) 10 (32.2%) 14 (46.6%)

    Ciprofloxacin 79 (89.7%) 38 (60%) 23 (64%) 25 (80.6%) 20 (66.6%)

    Doxycycline 61 (69.3%) 23 (36%) - 17 (54.8%) 21 (70%)

    Aztreonam - - 28 (78%) - -

    Table 4. Multidrug resistant pattern among significant clinical isolates of gram-negative bacilli.

    Combination of antibiotic Acinetobacter Pseudomonas Escherichia Klebsiella Total MDRbaumanii aeruginosa* coli Pnemoniae gram negative

    N=63 N=36 N=31 N=88 N=218

    5MDR(AMG+CEFT/FEP*/CAZ*+FQ+CARB+TETRA/TZP*) 22(35%) 14(38.8%) 2(6.45%) 30(34.09%) 68(31.1%)

    4MDR(AMG+CEFT/FEP*/CAZ*+FQ+CARB) 13(20.6%) 2(5.5%) 1(3.22%) 16(18.8%) 32(14.6%)

    3MDR(AMG+CEFT/FEP*/CAZ*+FQ) 0 0 3(9.6%) 0 0

    3MDR(CARB+CEFT/FEP*/CAZ*+FQ) 4(6.3%) 1(2.7%) 0 0 5(2.2%)

    3MDR(AMG+FQ+CARB) 0 0 0 0 0

    3MDR(AMG+CEFT/FEP*/CAZ*+CARB) 0 0 0 0 0

    Total MDR (%) 39(61.9%) 17(47.2%) 6(19.35%) 46(52.2%) 105(48.1%)

    MDR=Multidrug resistant, AMG=aminoglycosides, CEFT=Ceftriaxone, FQ=Fluoroquinolone, CARB=Carbapenum,TZP=Tazobactum-piperacillin, FEP=Cefepime, CAZ=Ceftazidime, *drugs for pseudomona

  • 84 . Infectious Diseases Journal of Pakistan

    patients. World J Crit Care Med 2016; 5(2):111-202. Ruppe E, Woerther P-L, Barbier. Mechanism of antimicrobial resistance

    in Gram negative bacilli. Ann.Intensive Care (2015); 5:213. REA-Raisin Network (2012) Surveillance of nosocomial infections in

    critically ill adult patients, France, 20124. Aliberti S et al. Multidrug-resistant pathogens in hospitalized patients

    coming from the community with pneumonia: a European perspective.Thorax 2013; 68:997–9

    5. Razazi K et al. Clinical impact and risk factors for colonization withextended spectrum beta-lactamase-producing bacteria in the intensivecare unit. Intensive Care Med 2012; 38(11):1769–78

    6. Torres A et al. Bacteremia and antibiotic-resistant pathogens in communityacquired pneumonia: risk and prognosis. Eur Respir J 2015; 45(5):1353–63

    7. Choi J.Y. et al.Trends in the distribution and antimicrobial susceptibilityof causative pathogens of device-associated infection in Korean intensivecare units from 2006 to 2013: results from the Korean NosocomialInfections Surveillance System (KONIS) .J Hosp Infection 2013; 92(4):363 – 71

    8. Center for Diseases Control and Prevention (2013) Threat report2013.http://www.cdc.gov. Accessed 13 Mar 2015

    9. Bassetti M, Righi E, Carnelutti A. Bloodstream infections in the IntensiveCare Unit. Virulence. 2016; 7(3):267-79

    10. Parajuli NP, Acharya SP, Mishra SK, Parajuli K, Rijal BP, Pokhrel BM.High burden of antimicrobial resistance among gram negative bacteriacausing healthcare associated infections in a critical care unit of Nepal.Antimicrobial Resistance and Infection Control. 2017; 6:67.

    11. Alekshun MN, Levy SB Molecular mechanisms of antibacterial multidrugresistance. Cell. 2007; 128(6):1037–50

    12. Wasswa P, Nalwadda CK, Buregyeya E, Gitta SN, Anguzu P, Nuwaha F.Implementation of infection control in health facilities in Arua district,Uganda: a cross-sectional study. BMC Infectious Diseases. 2015; 15:268.

    13. Magiorakos AP et al. Multidrug-resistant, extensively drug-resistant andpan drug-resistant bacteria: an international expert proposal for interimstandard definitions for acquired resistance. Clin Microbiol Infect. 2012;18 (3): 268-81

    14. Patel JB. Performance standards for antimicrobial susceptibility testing.Wayne, PA: Clinical and Laboratory Standards Institute; 2016.

    15. Bushra et al. Bacteremia: Prevalence and antimicrobial resistance profilingin chronic kidney diseases and renal transplant patients. Pak Med Assoc.2016; 66(6):705-9

    16. Siddiqui N-R, Qamar FN, Jurair H, Haque A. Multi-drug resistant gramnegative infections and use of intravenous polymxin B in critically illchildren of developing country: retrospective cohort study. BMC InfectiousDiseases. 2014; 14:626

    17. Bennett, J., Dolin, R., Blaser, M., Mandell, G. and Douglas, R. (2015).Mandell, Douglas, and Bennett's principles and practice of infectiousdiseases. Philadelphia: Elsevier Saunders.

    18. Sheth KV, Patel TK, Malek SS, Tripathi CB. Antibiotic sensitivity patternof bacterial isolates from the intensive care unit of a tertiary care hospitalin India. Trop J Pharm Res. 2012;11(6):991-99

    19. Bin Cai et al. Prevalence of Carbapenem-Resistant Gram-NegativeInfections in the United States Predominated by Acinetobacter baumanniiand Pseudomonas aeruginosa. J Infect Dis.2017; 4(3):176

    20. Yusuf et al. Emergence of antimicrobial resistance to Pseudomonasaeruginosa in the intensive care unit: association with the duration ofantibiotic exposure and mode of administration. Ann. Intensive Care.2017; 7(1):72

    21. Decicera Colombo OV et al. Trends of 9,416 multidrug-resistant Gramnegative bacteria. Rev. Assoc. Med. Bras. 2015; 61(3): 244-49.

    22. Masgala A, Kostaki K, Ioannnidis I. Multi Drug Resistant Gram NegativePathogens in Long Term Care Facilities: A Steadily Arising Problem. JInfect Dis Diagn.2015; 1:101

    As compared to Klebsiella, 35%(22/63) isolates of Acinetobacterbaumanii are multidrug resistant to these five antimicrobials.E.coli, the second commonest lactose fermenting gram-negativebacilli showed comparatively lesser degree of multidrugresistance. Pseudomonas aeruginosa isolates on the oppositehand are equally multidrug resistant as shown by (14/36) 38%of isolates displaying multi-drug resistance to five categoriesof antimicrobials. Nearly similar pattern of multidrug resistancehas been reported in different studies.21, 22

    There are certain limitations of this study. First, non- availabilityof adequate clinical data makes it a retrospective study.Colonization of surfaces by Pseudomonas and Acinetobactermakes it difficult to label these organisms as pathogens especiallywhen they are isolated from blood cultures. We are unable toexplore the outcome of patients suffering from hospital acquiredinfections again due to limited data. Third, in depth analysis oftreatment in cases of MDR infections has not been done. MDRorganisms defined in this study are subjected to changes as perupcoming guidelines and clinical efficacy of drugs when usedby clinicians. We can have entirely different pattern ofantimicrobial resistance once a different definition is applied.

    ConclusionAntimicrobial susceptibility of the three most common isolatesin our study has been restricted to carbapenems and colistin.Even carbapenem resistance is significantly higher, that makesit unsuitable to be used as an empirical antibiotic. The decreasingsensitivity of MDR gram negative bacteria to third generationcephalosporins and carbapenems leaves us with colistin as theonly option. Use of colistin has become a unlikeable necessityin spite of the cost and side effects pose by them.

    RecommendationsDetrimental effects of antimicrobial resistance surface asprolonged hospital stays, increased financial burden and mortalityrate. The main goal of hospital administrators around the worldshould be focused at making worthy efforts to reduceantimicrobial resistance and hospital acquired infection.

    Practicing antimicrobial surveillance is the need of the hour asit directs in generating an antibiogram which reflects our nationaldata. It also guides the clinician in choosing the type ofantimicrobial drug and appropriate duration of therapy.Antimicrobial surveillance cannot be achieved without an effectivehospital infection management policy with frequent revisions ofantimicrobial policy guideline. Thus, practicing antimicrobialstewardship can help us in curbing antimicrobial resistance.

    References1. Paramythiotou E,Routsi C. Association between infections caused by

    multidrug- resistant gram negative bacteria and mortality in critically ill

  • Volume 28 Issue 04 Oct - Dec 2019. 85

    CASE REPORT

    Corresponding Author: Hamzullah Khan,Associate Professor,Nowshera Medical College,NowsheraEmail: [email protected]

    Extremely Drug Resistant Pseudomonas in Qazi Hussain Ahmed Medical Complex, Nowshera, Pakistan.

    AbstractNosocomial infections are major health issues in developingas well as developed countries. The most common pathogensthat cause nosocomial infections are Staphylococcus aureus,Pseudomonas aeruginosa, and E. coli. Pseudomonas Aeruginosais an ubiquitous organism because of its extraordinary survivaland adaptation abilities in various environments like soil, water,sewage, hospitals etc. Among all gram-negative bacteria,Pseudomonas is a predominant opportunistic pathogen whichusually infects persons having some underlying diseases andcompromised immune status. Increasing multidrug resistanceamong nosocomial pathogens specially pseudomonas is alarmingand is a challenge for the health care providers in managementof various infectious diseases in hospital set up.

    Key WordsDrug Resistance, Psuedomonas, Opportunistic Infections

    Case ReportA 3 days old baby presented with Meningomyelocele with nomotor activities in the lower extremities presented to the Pediatricsurgery unit of Qazi Hussain Ahmed Medical complex. Thebaby born in a local private clinic. Child was admitted in thehospital 17/12/2017 for Meningomyelocele and operated on18/12/2017. Baby weight was 3 kg and well built otherwise(Figure 1). Daily dressing was in routine protocol along withtreatment of infection with antibiotics. Child was dischargedon 26/12/2017. The home take medications were ampicillinand cefuraxime during with vit A and paracetamol drops. Childwas re-admitted for oozing post operative wound to the sameunit on 03/01/2018. The child wound was open with oozing ofpus and was re-started on antibiotic cefuraxime 250mg BD,gentamicine 1-2mg/kg, Inj ampicillin+ cloxacillin 250mg BD,with local application of polymyxin B and fusidic acid. Pusswab for culture and sensitivity was sent to microbiology sectionon 03-01-2018.

    Grams stain showed Gran Negative Rods that was followedwith Culture on Macconkey agar. The plate was incubated at35C under aerobic conduction. After 24 hours growth of colonieswas obtained (figure 1). A spot Oxidase test was positive.Presumptive diagnosis made was Pseudomonas auriginosa.

    The colonies were inoculated on Mueller Hinton Agar as perCLSI (Clinical and Laboratory Standards Institutes) Guidelinesfor 24 hours. The accepted zones of sensitivity taken in

    Hamzullah Khan, Fazli Bari

    Nowshera Medical College, Nowshera, Pakistan.

    Figure 2. Figure showing sensitivity of conventional andnon conventional antibiotics against the Pseudomonasaeruginosa.

    Fig 1. Baby general look and growth of isolate on Macconkeyagar.

  • 86 . Infectious Diseases Journal of Pakistan

    consideration as per CLSI (Clinical Laboratory StandardInstitute) Guideline 20151. The pseudomonas bug was foundresistant to all conventional and non conventional antibioticsincluding (Ak-Amikacin, Mem-Meropenem, IPM-imepenum,CAZ-Ceftazadime, CTX-Cefotaxime, TZP-PiperacillinTazobactum, SCF-Cefperazone Sulbactum, AMC-AmoxicillinClavolinic acid) Lev- Levofloxacin, CN-Gentamycin and Cip-ciprofloxacin. Then non conventional drugs like, E-Erythromycin, Dox-Doxycyclin, SXT-Co-Triamaxazol andchloramphenicol,. We found that isolate was only sensitive toCT- Colistin Sulphate.

    DiscussionBaby born with congenital meningomylocele and was broughtto hospital for repair surgery. Various risk factors can becontributed to growth of multidrug resistant pseudomonas inhospital set up. Treatment of diseases with multidrug resistantpseudomonas. P. aeruginosa becomes more challenging forclinicians. The chromosomally encoded AmpC cephalosporinase,the outer membrane porin OprD, and the multidrug effluxpumps are particularly attributed to this therapeutic challengedealing with pseudomonas.2,3 In the hospital, P. aeruginosa canbe isolated from a variety of sources, including respiratorytherapy equipment, antiseptics, soap, sinks, mops, medicines,and physiotherapy and hydrotherapy pools.4

    The risk for acquiring XDR infections may be related to extrinsic,ecological characteristics of patients, such as the number ofcarriers in the same ward, the nurse-to-patient ratio, andcompliance with infection control measures as well as toindividual risk factors, such as patient characteristics and in-hospital events, including treatment with antibiotics.5

    Rates of antibiotic resistance in Pseudomonas aeruginosa isreported worldwide as a therapeutic challenge with some casesas with therapeutic dead end like the case we studied, as wehave no option/ no molecule to treat such like infections. TheExtremely drug-resistance (XDR) in P. aeruginosa isattributed/mediated by several mechanisms including multidrugefflux systems, enzyme production, outer membrane protein(porin) loss, and target mutations.6

    We observed that pseudomonas bug was resistant to allconventional antibiotics including (Ampicillin, Co-Amoxiclav,Cefradine, Cefotaxime, Cefuraxime, Amikacine, Amipenem,Pipracilline Tazobactum, Cefoperazone sulbactum andceftazadime) and non conventional drugs like chloramphenicol,erythromycin, doxycycline, and co-trimoxazole were also noteffective. However, it was found sensitive to only CholistineSulphate which can’t be given as monotherapy and the sametime its availability is an issue.P. aeruginosa exhibits the highest rates of resistance for the

    fluoroquinolones, with resistance to ciprofloxacin andlevofloxacin ranging from 20 to 35%. Specially in ICU patients.P. aeruginosa isolates from ICU patients also confers higherrates of b-lactam resistance than general trends for hospitalizedpatients. Among the aminoglycosides, most studies have focusedon gentamicin, with resistance rates ranging from 12 to 22%.7,8

    We recommended to the clinician to start on liposomal cholistinesulphate along with combination of pipracillin tazobactum ascholistine sulphate is not advised as monotherpay as per CLSIrecommendation.

    After reporting of this isolate, we informed the hospitaladministration, unit in-charge and OT in-charge about theemergence of this super bug, with the request to fumigate theoperation theatre as well as the ward and to isolate the baby.

    We suggest this XDR Pseudomonas infection can be preventedin hospitals with the following general preventive measure ifproperly adopted including proper scientific hand washing,fumigation of the operation theatre and ward, reducing thenumber of visitors to the ward, minimizing the irrational useof antibiotics and prescribing antibiotic after culture andsensitivity.

    We also planned in departmental meeting to start cultures onweekly basis from OT and surgical wards and to report it tothe administration for further necessary actions.

    References1. Clinical Laboratory standard institute. M100-S25. Performance standard

    for antimicrobialsusceptablity testing: twenty fifth informationalsupplement. CLSI, Wayne USA, 2015;35(3):66-72.

    2. Lister PD, Wolter DJ, Hanson ND. Antibacterial-Resistant Pseudomonasaeruginosa: Clinical Impact and Complex Regulation of ChromosomallyEncoded Resistance Mechanisms. Clin Microbiol Rev 2009; 22(4):582–610.

    3. Abdalhamid, B., P. A. Wickman, and N. D. Hanson. Correlation of ampCinduction with PBP binding in Enterobacter cloacae, abstr. C1-2211.2005. Abstr. 45th Intersci. Conf. Antimicrob. Agents Chemother.,Washington, DC

    4. Pollack, M. Pseudomonas aeruginosa, p. 1820-2003. In G. L. Mandell,R. Dolan, and J. E. Bennett (ed.), Principles and practices of infectiousdiseases. Churchil l Livingstone, New York, NY. 1995.

    5. Carmeli, Y., G. M. Eliopoulos, and M. H. Samore. Antecedent treatmentwith different antibiotic agents as a risk factor for vancomycin-resistantEnterococcus. Emerg. Infect. Dis 2002. 8:802-807.

    6. Tam VH, Hirsch EB. Impact of multidrug-resistant Pseudomonasaeruginosa infection on patient outcomes. Expert Rev PharmacoeconOutcomes Res 2010 Aug; 10(4): 441–451.

    7. Poirel, L., M. Van De Loo, H. Mammeri, and P. Nordmann. 2005.Association of plasmid-mediated quinolone resistance with extendedspectrum beta-lactamase VEB-1. Antimicrob. Agents Chemother 49:30913094.

    8. Poole, K. 2005. Aminoglycoside resistance in Pseudomonas aeruginosa.Antimicrob. Agents Chemother 49:479-487.

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