941564. cgfjhgf fghjfgafag bagfajanabda. cgdfjhgdf cjhdfgf

8/10/2019 941564. cgfjhgf fghjfgafag bagfajanabda. cgdfjhgdf cjhdfgf

1/8

Research ArticleAntimicrobial Resistance Trends among Community-AcquiredRespiratory Tract Pathogens in Greece, 20092012

Sofia Maraki and Ioannis S. Papadakis

Department of Clinical Microbiology, Parasitology, Zoonoses and Geographical Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece

Correspondence should be addressed to Soa Maraki; [email protected]

Received August ; Accepted November ; Published January

Academic Editors: D. P. Levine and G. A. Rocha

Copyright S. Maraki and I. S. Papadakis. Tis is an openaccess article distributed under the Creative Commons AttributionLicense, whichpermits unrestricted use, distribution, andreproduction in anymedium, providedthe original workis properlycited.

Te aim o the present study was to determine the antimicrobial resistance trends o respiratory tract pathogens isolated rompatients with community-acquired respiratory tract inections (CARIs) in Crete, Greece, over a -year period (). Atotal o community-acquired respiratory pathogens were isolated during the study period. Streptococcus pneumoniaewas themost common organism responsible or .% o CARIs, ollowed byHaemophilus inuenzae(.%) andMoraxella catarrhalis(.%). AmongS. pneumoniae, the prevalence o isolates with intermediate- and high-level resistance to penicillin was .% and.%, respectively. Macrolide resistance slightly decreased rom .% over the period - to .% over the period -. Multiresistance was observed among (.%) penicillin nonsusceptible isolates. A nonsignicant increase in resistance o

H. inuenzaeisolates was noted or-lactams, cotrimoxazole, and tetracycline. Among the M. catarrhalistested, producedbeta-lactamase and wereresistant to ampicillin. Macrolideresistance decreasedover the study period. All isolates weresusceptibletoamoxicillin + clavulanic acid,chloramphenicol,riampicin, and the uoroquinolones. Although a decreasing trendin the prevalenceo resistance o the three most common pathogens involved in CARIs was noted, continuous surveillance o antimicrobialsusceptibility at the local and national level remains important, in order to guide appropriate empirical antimicrobial therapy.

1. Introduction

Community-acquired respiratory tract inections (CARIs)such as acute otitis media, acute sinusitis, acute exacerbationso chronic bronchitis, and community-acquired pneumoniaare very common causes o morbidity and are among the

leading reasons or physicians office visits worldwide [].Due to the severity o these inections and the difficultiesin determining the bacterial etiology and the antimicrobialsusceptibility, treatment is ofen empirical, consisting usuallyo orally administered agents. Te choice o empiric antimi-crobial chemotherapy is guided by the clinical presentation,the severity o the inection, and epidemiologic data, com-prising the causative organisms and their susceptibility toantimicrobial agents [,].

Streptococcus pneumoniae, Haemophilus inuenzae, andMoraxella catarrhalis are the major pathogens implicatedin community-acquired respiratory tract inections. Teincreasing prevalence o antimicrobial resistance among

these species remains a global problem complicating themanagement o CARIs [,].

O particular concern are the emergence and dissemi-nation o S. pneumoniae strains resistant to penicillin andmultidrug resistant (MDR) to several antibiotic classes [].InH. inuenzaeandM. catarrhalis -lactamase (BL) production

has been the primary mechanism or bacterial resistanceto beta-lactams [, ]. However, rare -lactamase negativeampicillin-resistant (BLNAR) H. inuenzae isolates havebeen reported [].

In the present study, we describe the antimicrobial sus-ceptibility patterns o community-acquired respiratory tractpathogens that were isolated in the microbiology laboratorythe last years.

2. Materials and Methods

We prospectively tested in vitroall isolates oH. inuenzae,S. pneumoniae, andM. catarrhalis that were recovered rom

Hindawi Publishing Corporatione Scientific World JournalVolume 2014, Article ID 941564, 7 pageshttp://dx.doi.org/10.1155/2014/941564
http://dx.doi.org/10.1155/2014/941564http://dx.doi.org/10.1155/2014/941564


2/8

Te Scientic World Journal

: Distribution o community-acquired respiratory pathogens by study year ().

S. pneumoniae (.%) (.%) (%) (.%) (.%)

H. inuenzae (.%) (.%) (.%) (.%) (.%)

M. catarrhalis (.%) (.%) (.%) (.%) (.%)

otal

patients with CARIs at the University Hospital o Heraklionover the period //. One bacterial isolate wastested per patient. Isolates collected either rom nonhospital-ized patients or rom hospitalized patients within hourso admission were included. Organisms were recovered rompatients with sinusitis, otitis media, community-acquiredpneumonia, acute bacterial exacerbation o chronic bronchi-tis, and acute exacerbation o chronic obstructive airwaysdisease. Blood, pleural uid, bronchoalveolar uid, sputum,middle ear uid, and sinus aspirate cultures were consideredacceptable sources or study isolates.

.. Identication and Antimicrobial Susceptibility Testing.S. pneumoniae was identied on the basis o colony andmicroscopic morphology, hemolytic reactions on sheepblood agar medium, catalase test, optochin susceptibility,bile solubility, and biochemical prole using the Vitek automated system (BioMerieux). H. inuenzae was iden-tied on the basis o hemolytic reactions on horse bloodagar, growth requirement or X and V actors, and by theuse o Vitek automated system (BioMerieux, Marcy lEtoile, France). Identication o M. catarrhalis was basedon colony and microscopic morphology, oxidase test, andby the use o Vitek automated system (BioMerieux). ForS. pneumoniaeisolates, minimum inhibitory concentrations(MICs) were determined using theE-test method, or peni-cillin, ceuroxime, ceotaxime, cefriaxone, ceepime, im-ipenem, meropenem, erythromycin, clarithromycin, roxi-thromycin, azithromycin, clindamycin, ciprooxacin, lev-ooxacin, moxioxacin, chloramphenicol, tetracycline, cot-rimoxazole (SX), and vancomycin. Results were inter-preted according to the Clinical and Laboratory Stan-dards Institute criteria (CLSI) []. Te double-disk diffusionmethod with erythromycin ( g) and clindamycin ( g)(Bio-Rad, Marnes-la-Coquette, France) and MIC data wereused or the determination o macrolideresistance phenotype

[]. Resistance to both erythromycin and clindamycin ischaracteristic o a cMLS

Bphenotype, while blunting o the

clindamycin inhibition zone near the erythromycin discis indicative o an iMLS

B phenotype. Resistance to ery-

thromycin and susceptibility to clindamycin with no bluntingare characteristic o the M phenotype. Multiresistance wasdened as resistance to three or more classes o antibiotics.

ForH. inuenzae and M. catarrhalis antimicrobial sus-ceptibility tests were perormed by employing the disk diffu-sion method andthe results were interpreted according to the CLSI criteria [,]. Intermediate isolates were groupedalong with resistant isolates. Te antibiotics that were testedagainst H. inuenzae isolates are the ollowing: ampicillin,

amoxicillin + clavulanic acid, clarithromycin, chloram-phenicol, tetracycline, SX, ciprooxacin, ooxacin, andmoxioxacin. Te antibiotics that were tested against M.catarrhalis isolates are the ollowing: amoxicillin, amoxicillin+ clavulanic acid, chloramphenicol, tetracycline, clar-ithromycin, SX, riampicin, ciprooxacin, and moxioxa-cin. Beta-lactamase (BL) production was assayed bythenitrocen test (Oxoid, Basingstoke, UK). BLNARH. inu-enzae strains were dened as BL-negative strains that wereresistant to ampicillin (MIC g/mL) [].

In order to test or differences in the antibiotic suscepti-bility patterns between the earlier and later study years ora given antibiotic, we compared the resistance proles orespiratory isolates o the period - with those o theperiod -.

.. Statistical Analysis. Statistical analysis was conductedby Fishers exact and Kruskal-Wallis tests, as appropriate.Statistical signicance was set at < 0.05. All analyses wereperormed with Graphpad Prism, V. (GraphPad SofwareInc., CA, USA).

3. Results

.. Bacterial Isolates and Patients Demographics. A total oS. pneumoniae, H. inuenzae, and M. catarrhaliswere isolated during the period // rom patientswith CARIs. Te distribution o respiratory pathogens bystudy year is shown in able . Sixty-three percent o allisolates were obtained rom male patients (able ). Mosto the S. pneumoniae strains were most requently isolatedrom pediatric patients years o age, while H. inuenzaeandM. catarrhaliswere derived rom adults years o age(able ).

.. Antibiotic Resistance among S. pneumoniae Isolates. In

vitro susceptibility data or antimicrobial agents are pre-sented inable . Te proportion o penicillin nonsuscep-tible (PNSP) isolates was .% (.% with intermediateresistance and .% with high-level resistance). Isolateswith intermediate and high-level resistance became morerequent over time, rom .% over the period to, increased to .% over the years to , whileisolates with high-level resistance decreased the second halo the study period ( = 0.09) (able ). Resistance tothe third generation cephalosporins decreased over the twotwo-year time periods, rom .% to .% or ceotaximeand rom .% to .% or cefriaxone. Similarly, there wasa trend or nonsignicant decrease in ceepime resistance


3/8


: Numbers o isolates oH. inuenzae,S. pneumoniae, andM. catarrhalis, grouped according to gender and age.

S. pneumoniae( = 261)

H. inuenzae( = 260)

M. catarrhalis( = 67)

Gender

Male

Female

Age groups(years)

(including intermediately and ully resistant strains) thatdecreased rom .% to % ( = 0.15). Resistance toerythromycin was detected in isolates (.%). Amongthem, M and cMLS

Bphenotypes were observed in (.%)

and (.%) strains, respectively, by the use o the doubledisk approximation test. Additionally, strains (.%) withtheiMLS

Bphenotype weredetected.Erythromycin resistance

decreased rom .% over the years to to .%over the period to , but this was not signicant ( =1.00) (able ). Only two isolates, one in each study period,were resistant to newer uoroquinolones, while all isolateswere susceptible to vancomycin (able ).

Multiresistance was observed among (.%) PNSPstrains. Te predominant phenotype o multidrug resistancewas nonsusceptible to penicillin, erythromycin, clindamycin,and tetracycline (.%), and the second most requentphenotype was nonsusceptible to penicillin, erythromycin,tetracycline, and SX (.%) (able ).

.. Antibiotic Resistance among H. inuenzae Isolates. O theH. inuenzaeisolates, (.%) produced-lactamase.Ampicillin-resistant isolates represented %, while amox-icillin + clavulanic acid-resistant isolates were only .%.Overall, BLNAR strain was isolated. A nonsignicantincrease in resistance o H. inuenzae isolates was notedbetween the two study periods or ampicillin and amoxicillin

+ clavulanic acid. Te same was true or clarithromycin, SX,and tetracycline (able ).

.. Antibiotic Resistance among M. catarrhalis Isolates.Among the isolates tested, almost hal o them ( isolates)were resistant to ampicillin and produced beta-lactamase.Macrolide resistance decreased rom .% in - to.% in -. Te reverse trend was noted or cotrimox-azole. Only one isolate was resistant to tetracycline and all isolates were susceptible to amoxicillin + clavulanic acid,chloramphenicol, riampicin, and the two uoroquinolonestested (able ).

4. Discussion

Te results o the present study provide an update on resis-tance trends amongst pathogens that cause CARIs in ourarea. Increasingly, resistance oS. pneumoniae to penicillinis o special concern, because this agent has been considered

the therapy o choice or pneumococcal CARIs, due to itsefficacy and low cost [,]. Although resistant strains oS.pneumoniaeare detected universally, the incidence o resis-tance varies markedly between countries and regions. Datarom the Alexander project reported penicillin resistancelevels inS. pneumoniaeranging rom .% in Eastern Europethrough % in the USA to .% in several parts o Asia in [].

Te rst study conducted in Greece in the early ,evaluating the antimicrobial susceptibilities o , clini-cal isolates o S. pneumoniae deriving rom patients withcommunity-acquired pneumonia, reported resistance rateso % or penicillin []. A recent study rom the same

centre showed an increase o .% in penicillin resistance[]. In the present study, the percentage o intermediatelyresistant and resistant isolates decreased rom .% to .%over the two study periods. More specically, the percentageo highly resistant isolates dropped rom .% to .%.Additionally, the low rates o resistance to third-generationcephalosporins avour their use as the rst-choice empiricaltreatment or community-acquired pneumonia necessitatinghospital admission []. In the present study .% o PNSPstrains were ound to be multidrug resistant, a rate similar tothat previously reported []. Riedel et al. in their study in European countries reported overall MDR to .%, varyingrom % in Denmark to .% in Greece [].

Resistance to macrolides, which reached .% amongpneumococcal isolates, renders empirical monotherapy witha macrolide not appropriate or treatment o patientswith community-acquired pneumonia. Te US (IDSA/AS)guidelines recommend that in regions where macrolide-resistance exceeds %, macrolide monotherapy is not appro-priate even or patients without comorbidities []. Te Mphenotype encoded by the me gene predominated in Crete,a eature also prevailing in other areas in Greece, in theUnited States, and Canada but much rarer in other Europeancountries, where the MLS

B phenotype, characterized by

resistance to macrolides, lincosamides, and streptogramin,

is most commonly encountered []. Te high requencyo resistance to macrolides is due to their increased outpa-tient use or CARIs. Te relationship between macrolideresistance inS. pneumoniaeand macrolide consumption hasbeen shown by several investigators, reporting low resistancerates in low consuming areas as Scandinavia and high inMediterranean countries with increased macrolide use, suchas France, Spain, and Italy, where the respective prevalenceare %, %, and %% [,].

Overall, isolates (.%) were resistant to cotrimoxa-zole, which is lower than that ound in our previous study othe period []. Tis nding is likely due to thedecreased outpatient consumption o the drug in our area,


4/8


: Comparison o antibiotic resistance rates inS. pneumoniaisolates over the periods - and -.

- -

Antibiotic MIC MIC Range % % % MIC MIC Range % % % value

Penicillin .


5/8


: rends in antibiotic resistance oH. inuenzaeandM. catarrhalisisolates.

(a) Haemophilus inuenza

Antimicrobial agent

= 79resistant

= 51

resistant

= 61

resistant

= 69

resistant

- (A) = 130resistant

- (B) = 130resistant

valueA versus B

Ampicillin (.%) (.%) (.%) (.%) (.%) (.%) .Amoxicillin + CA (%) (%) (%) (.%) (.%) (.%) .

Clarithromycin (.%) (.%) (.%) (.%) (.%) (.%) .

Chloramphenicol (%) (%) (%) (%) (%) (%) NA

etracycline (.%) (.%) (.%) (.%) (.%) (.%) .

Cotrimoxazole (.%) (.%) (.%) (.%) (.%) (.%) .

Ciprooxacin (%) (%) (%) (%) (%) (%) NA

Ooxacin (%) (%) (%) (%) (%) (%) NA

Moxioxacin (%) (%) (%) (%) (%) (%) NA

CA: clavulanic acid; NA: not applicable.

(b) Moraxella catarrhalis

Antimicrobial agent

= 20resistant

= 13

resistant

= 18

resistant

= 16

resistant

- (A) = 33

resistant

- (B) = 34

resistant

valueA versus B

Amoxicillin (%) (.%) (.%) (%) (.%) (%) .

Amoxicillin + CA (%) (%) (%) (.%) (%) (%) NA

Chloramphenicol (%) (%) (%) (%) (%) (%) NA

etracycline (%) (%) (%) (.%) (%) (.%) .

Clarithromycin (%) (.%) (.%) (.%) (.%) (.%) .

Cotrimoxazole (%) (.%) (.%) (.%) (.%) (.%) .

Riampicin (%) (%) (%) (%) (%) (%) NA

Ciprooxacin (%) (%) (%) (%) (%) (%) NA

Moxioxacin (%) (%) (%) (%) (%) (%) NA

CA: clavulanic acid; NA: not applicable.

isolates has been shown []. etracycline resistance waslow (%), reecting the tendency in recent years not to useolder tetracyclines or the treatment o CARIs. All isolatesare susceptible to uoroquinolones. Fluoroquinolones stillremain among the antimicrobial agents that are most power-ul againstH. inuenzae in vitro and are also highly effectiveas treatment o respiratory tract inections [], althoughresistance has been recognized [], and therapeutic ail-ures in patients with community-acquired pneumonia havebeen associated with levooxacin resistance in H. inuenzae

[]. Overall, .% o the M. catarrhalis isolates were -lactamase positive. Te-lactamases which coner resistanceto ampicillin have been characterized as BRO- and BRO-orM. catarrhalis and are inhibited by clavulanic acid andthe combination o amoxicillin + clavulanic acid has beenshown to be highly active against these species []. Since therst report o-lactamase-producingM. catarrhalis in [], the percentage o these strains has increased worldwideover the years, exceeding % in some countries [,,].Apart rom macrolides and cotrimoxazole all antimicrobialshad goodin vitroactivity against this organism.

In conclusion, there is a decreasing trend in the preva-lence o resistance o the three most common pathogens

involved in CARIs. However, continuous surveillance atlocal and national levels remains important to detect anyurther changes in pathogens and monitor any changesin antimicrobial susceptibility among the major respiratorypathogens responsible or CARIs.

Conflict of Interests

Te authors declare that there is no conict o interestsregarding the publication o this paper.

References

[] C. W. Stratton, An overview o community-acquired respira-tory tract inections,Advanced Studies in Pharmacy, vol. , no., pp. , .

[] . M. File Jr., J. Garau, F. Blasi et al., Guidelines or empiricantimicrobial prescribing in community-acquired pneumonia,Chest, vol. , no. , pp. , .

[] K. P. Klugman, D. E. Low, J. Metlay, J.-C. Pechere, and K. Weiss,Community-acquired pneumonia: new management strate-gies or evolving pathogens and antimicrobial susceptibilities,


6/8


International Journal of Antimicrobial Agents, vol. , no. , pp., .

[] C. Alpuche, J. Garau, and V. Lim, Global and local variationsin antimicrobial susceptibilities and resistance developmentin the major respiratory pathogens, International Journal ofAntimicrobial Agents, vol. , no. , pp. , .

[] J.-H. Song and D. R. Chung, Respiratory inections due todrug-resistant bacteria, Infectious Disease Clinics of NorthAmerica, vol. , no. , pp. , .

[] J. Aspa, O. Rajas, and F. R. de Castro, Pneumococcal antimi-crobial resistance: therapeutic strategy and management incommunity-acquired pneumonia,Expert Opinion on Pharma-cotherapy, vol. , no. , pp. , .

[] S. ristram, M. R. Jacobs, and P. C. Appelbaum, Antimicrobialresistance in Haemophilus inuenzae, Clinical MicrobiologyReviews, vol. , no. , pp. , .

[] . F. Murphy and G. I. Parameswaran, Moraxella catarrhalis, ahuman respiratory tract pathogen,Clinical Infectious Diseases,vol. , no. , pp. , .

[] Clinical and Laboratory Standards Institute (CLSI), Per-ormance standards or antimicrobial susceptibility testing;wenty-second inormational supplement, M-S, CLSI,Wayne, Pa, USA, .

[] Clinical and Laboratory Standards Institute (CLSI), Dilutionand Disk Susceptibility Testing of Infrequently Isolated or Fastid-ious Bacteria, Approved guideline M-A. CLSI, Wayne, Pa,USA, nd edition, .

[] S. Kanavaki, S. Karabela, E. Marinis, and N. J. Legakis, Antibi-otic resistance o clinical isolates oStreptococcus pneumoniaein Greece,Journal of Clinical Microbiology, vol. , no. , pp., .

[] S. Kanavaki, E. Mantadakis, S. Karabela et al., Antimicrobial

resistance o Streptococcus pneumoniae isolates in Athens,Greece, European Journal of Clinical Microbiology and Infec-tious Diseases, vol. , no. , pp. , .

[] L. R. Peterson, Penicillins or treatment o pneumococcalpneumonia: does in vitro resistance really matter? ClinicalInfectious Diseases, vol. , no. , pp. , .

[] S. Maraki, E. Mantadakis, and G. Samonis, Serotype dis-tribution and antimicrobial resistance o adult Streptococcuspneumoniaeclinical isolates over the period in Crete,Greece,Chemotherapy, vol. , no. , pp. , .

[] S. Riedel, S. E. Beekmann, K. P. Heilmann et al., Antimicrobialuse in Europe and antimicrobial resistance in Streptococcuspneumoniae, European Journal of Clinical Microbiology and

Infectious Diseases, vol. , no. , pp. , .

[] L. A. Mandell, R. G. Wunderink, A. Anzueto et al., Inec-tious Diseases Society o America/American Toracic SocietyConsensus Guidelines on the management o community-acquired pneumonia in adults,Clinical Infectious Diseases, vol., supplement , pp. SS, .

[] G. Poulakou, I. Katsarolis, I. Matthaiopoulou et al., Nationwidesurveillance oStreptococcus pneumoniaein Greece: patterns oresistance and serotype epidemiology,International Journal ofAntimicrobial Agents, vol. , no. , pp. , .

[] A. Marchese and G. C. Schito, Resistance patterns o lowerrespiratory tract pathogens in Europe, International Journal ofAntimicrobial Agents, vol. , supplement , pp. SS, .

[] D. J. Farrell, I. Morrissey, S. Bakker, and D. Felmingham,Molecular characterization o macrolide resistance mecha-nismsamongStreptococcus pneumoniaeand Streptococcuspyo-genes isolated rom the PROEK - study,Journal ofAntimicrobial Chemotherapy, vol. , supplement , pp. ,.

[] M. Bergman, S. Huikko, P. Huovinen, P. Paakkari, H. Seppala,and Te Finnish Study Group or Antimicrobial resistance(FiRe Network), Macrolide and azithromycin use are linkedto increased macrolide resistance in Streptococcus pneumoniae,Antimicrobial Agents and Chemotherapy, vol. , no. , pp., .

[] F. Baquero, G. Baquero-Artigao, R. Canton, and C. Garca-Rey,Antibiotic consumption and resistance selectionStreptococcuspneumoniae, Journal of Antimicrobial Chemotherapy, vol. ,supplement , pp. , .

[] C. Garca-Rey, L. Aguilar, F. Baquero, J. Casal, and R. Dal-Re, Importance o local variations in antibiotic consumptionand geographical differences o erythromycin and penicillinresistance in Streptococcus pneumoniae, Journal of Clinical

Microbiology, vol. , no. , pp. , .[] P. Karpanoja, S. . Nyberg, M. Bergman, Te Finnish

Study Group or Antimicrobial resistance (FiRe Network) etal., Connection between trimethoprim-sulamethoxazole andresistance in Streptococcus pneumoniae, Haemophilus inuen-zae, and Moraxella catarrhalis, Antimicrobial Agents andChemotherapy, vol. , no. , pp. , .

[] M. W. Pletz, M. van der Linden, H. von Baum, C. B. Duesberg,K. P. Klugman, and . Welte, Low prevalence o uoro-quinolone resistant strains and resistance precursor strainsin Streptococcus pneumoniae rom patients with community-acquiredpneumonia despitehigh uoroquinolone usage, Inter-national Journal of Medical Microbiology, vol. , no. , pp. , .

[] C. Garca-Rey, J. E. Martn-Herrero, and F. Baquero, Antibioticconsumption and generation o resistance in Streptococcuspneumoniae: the paradoxical impacto quinolones in a complexselective landscape,Clinical Microbiology and Infection, vol. ,supplement , pp. , .

[] H. J. Adam, D. J. Hoban, A. S. Gin, and G. G. Zhanel,Association between uoroquinolone usage anda dramatic risein ciprooxacin-resistantStreptococcus pneumoniaein Canada,,International Journal of Antimicrobial Agents, vol., no. , pp. , .

[] E. J. C. Goldstein and S. M. Garabedian-Ruffalo, Widespreaduse o uoroquinolones versus emerging resistance in pneumo-cocci,Clinical Infectious Diseases, vol. , no. , pp. ,.

[] J. P. Lynch III and G. G. Zhanel, Streptococcus pneumoniae:does antimicrobial resistance matter?Seminars in Respiratoryand Critical Care Medicine, vol. , no. , pp. , .

[] J. M. Blondeau, X. Zhao, G. Hansen, and K. Drlica, Mutantprevention concentrations o uoroquinolones or clinical iso-lates oStreptococcus pneumoniae, Antimicrobial Agents andChemotherapy, vol. , no. , pp. , .

[] D. P. Koferidis, G. Notas, S. Maraki et al., Antimicrobialsusceptibilities o Haemophilus inuenzae clinical strainsisolated rom the island o Crete, Greece, Chemotherapy, vol., no. , pp. , .

[] M. R. Jacobs, D. Felmingham, P. C. Appelbaum, and R. N.Gruneberg, Te Alexander Project : susceptibilityo


7/8


pathogens isolated rom community-acquired respiratory tractinection to commonly used antimicrobial agents,Journal ofAntimicrobial Chemotherapy, vol. , no. , pp. , .

[] D. Hoban and D. Felmingham, Te PROEK surveillancestudy: antimicrobial susceptibility oHaemophilus inuenzaeand Moraxella catarrhalis rom community-acquired respira-tory tract inections, Journal of Antimicrobial Chemotherapy,vol. , supplement , pp. , .

[] H. Seki, Y. Kasahara, K. Ohta et al., Increasing prevalence oampicillin-resistant, non-beta-lactamase-producing strains oHaemophilus inuenzae in children in Japan, Chemotherapy,vol. , no. , pp. , .

[] A. Jain, P. Kumar, andS. K. Agarwal, Highnasopharyngeal car-riage o-lactamase-negative ampicillin-resistantHaemophilusinuenzae in north Indian school-going children, Journal ofInfection and Chemotherapy, vol. , no. , pp. , .

[] M. R. Jacobs, Increasing antibiotic resistance among otitismedia pathogens and their susceptibility to oral agents basedon pharmacodynamic parameters,Pediatric Infectious DiseaseJournal, vol. , , supplement, pp. SS, .

[] A. Senok, M. Al-Zarouni, J. Al-Najjar, A. Nublusi, and D.Panigrahi, Antimicrobial resistance amongStreptococcus pneu-moniae and Haemophilus inuenzae isolates in the UnitedArab Emirates: ,Journal of Infection in DevelopingCountries, vol. , no. , pp. , .

[] J. A. Garca-Rodrguez, F. Baquero, J. Garca de Lomas, andL. Aguilar, Antimicrobial susceptibility o Haemophilusinuenzae isolates rom respiratory tract inections in Spain.Results o a year (-) multicenter surveillance study,Infection, vol. , no. -, pp. , .

[] S. L. Barriere and J. A. Hindler, Ciprooxacin-resistantHaemophilus inuenzae inectionin a patient with chronic lungdisease,Annals of Pharmacotherapy, vol. , no. , pp. ,.

[] . Bastida, M. Perez-Vazquez, J. Campos et al., Levooxacintreatment ailure in Haemophilus inuenzae pneumonia,Emerging Infectious Diseases, vol. , no. , pp. , .

[] A. A. Kadry, S. I. Fouda, N. A. Elkhizzi, and A. M. Shibl,Correlation between susceptibility and BRO type enzyme oMoraxella catarrhalisstrains,International Journal of Antimi-crobial Agents, vol. , no. , pp. , .

[] B. E. Malmvall, J.E. Brorsson,and J.Johnsson, In vitro sensitiv-ity to penicillin V and lactamase production oBranhamellacatarrhalis, Journal of Antimicrobial Chemotherapy, vol. , no., pp. , .


8/8

Submit your manuscripts at

http://www.hindawi.com

Documents

941564. cgfjhgf fghjfgafag bagfajanabda. cgdfjhgdf cjhdfgf