Community Acquired Pneumonia - A Malaysian Perspective · PDF fileCONTINUING MEDICAL EDUCATION Community Acquired Pneumonia - AMalaysian Perspective C K Liam, FRCP Department ofMedicine,

CONTINUING MEDICAL EDUCATION

Community Acquired Pneumonia - A MalaysianPerspective

C K Liam, FRCP

Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur

Introduction

Community acquired pneumonia (CAP) is a commonillness and potentially life threatening especially inolder adults and those with co-morbid disease. It is amajor cause of morbidity and death worldwide.Recognising the clinical importance of CAP, manycountries have developed national guidelines for themanagement of this conditionl",3.4.5,6.7. In Malaysia, theMalaysian Thoracic Society together with the Ministryof Health and the Academy of Medicine, Malaysia aredeveloping guidelines for the management of CAP inadults.

The microbial aetiology of community acquiredpneumoniaAlthough many microorganisms have been associatedwith CAP, it is a small range of key pathogens thatcause most cases. Streptococcus pneumoniae(pneumococcus) is the most frequently identifiedpathogen, with the highest incidence of this organismreported in studies that used urinary antigen detection.Apart from Streptococcus pneumoniae, a great deal ofliterature in Western countries has reportedHaemophilus injluenzae, atypical pathogensChlamydia pneumoniae, Mycoplasma pneumoniae,Legionella pneumophila and viruses (influenza virus,adenovirus, respiratory syncytial virus, parainfluenzavirus coronavirus) as the common pathogens ofCAP3,~.8,9,lO,ll. Gram-negative bacilli (Enterobacteriaceaeand pseudomonadas) are the cause of CAP in patientswho have had previous antimicrobial treatment or whohave pulmonary comorbidities)1'. In one study, 33% ofhospitalized CAP patients with unknown aetiologydiagnosed by routine methods were found to due toStreptococcus pneumoniae based on findings from

transthoracic needle lung aspiration, suggesting thatmany patients without a known pathogen havepneumococcal infection13

•

The microbial aetiological distribution of CAP reportedin the literature depends on the patient population, thegeographical region, the intensity of investigationscarried out and the occurrence of epidemics ofinfection. Even when carefully sought for in largeprospective studies, the putative causative organismremains unknown in about half of all patients with CAP.In an observational study that assessed the 'real-world'practice from several centres in the USA, only 6% ofoutpatients and a quarter of inpatients with CAP hadthe cause of their disease definedl4. Reasons for failureto identify the aetiological agent include prior treatmentwith antibiotics, unusual pathogens that gounrecognized, viral infections, non-infectious mimic ofCAP, and pathogens that are currently not identified orrecognized. .

The microbial aetiology of community acquiredpneumonia in patients requiring hospitalisationThe results of some studies on CAP requiringhospitalization from United Kingdom, the remainder ofEurope, Australia and New Zealand, North America andAsia are compared in Table 1. The aetiology of CAP inJapan and Korea does not differ markedly whencompared with that of Western countries except for thelow incidence of Legionella pneumonial5.l6.17. The lowincidence of Legionella pneumonia is also found in theother Asian countries which could have been due tolimitations of laboratory tests used. The epidemiologicdata from Bangkokl6 indicate that the microbial agentscausing CAP in Thailand, in general, are not differentfrom those in Western countries.

This article was accepted: 18 August 2004Corresponding Author: Liam Chong Kin, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur

Med J Malaysia Vol 60 No 2 June 2005 249


In the Japanese series, Chlamydia pneumoniae wasidentified in 3%15 and 7.5%20 of the cases, respectively.In the AsiACAP study" which was conducted fromOctober 2001 - December 2002 in 12 urban tertiarymedical centres in Asia (Beijing, Shanghai, Seoul,Taipei, Hong Kong, Bangkok, Manila, Kuala Lumpur,Petaling Jaya and Jakarta involving 1756 out- and inpatients aged 2 years and above, paired sera (acute andconvalescent) were obtained from 1374 patients(78.2%) [children up to 15 years (448 patients), adults(from age 15 years and above) (926 patients)].Infection rates based on 2:4-fold rise in antibody titrebetween acute and convalescent sera were found to be9.4% for Mycoplasma pneumoniae, 4.3% for Chlamydiapneumoniae and 6.2% for Legionella pneumophila. Theoverall infection rate for atypical pathogens is 19.9%.

A number of studies in Asia where the prevalence oftuberculosis is high have shown that infection due toMycobacterium tuberculosis may commonly present asan apparent CAP'S.21,23,24. In a study conducted inArgentina, Mycobacterium tuberculosis was identifiedin 2,8% of 253 patients with moderate CAp26. One 22 ofthe Malaysian studies excluded patients withtuberculosis while in the other two studies, tuberculosisaccounted for 15.3% and 4.8% of the cases,respectively23,24. Although pulmonary tuberculosis is achronic respiratory infection, it can present as CAP andit should be a differential diagnosis in areas wheretuberculosis is endemic.

In studies conducted in Malaysia, 2 out of 127 0.6%)patients in the Kuala Lumpur series had melioidosis;22while Burkholderia pseudomallei was not isolated inany patient in the Penang series23. In the Bangkokstudy,20 Burkholderia pseudomallei was identified in1.4% of the cases, However, in rural NortheasternThailand, Burkholderia pseudomallei was identified in15.4% of the patients hospitalised for CAP'9.Burkholderia pseudomallei should be considered acausative organism in patients with CAP in ruralSoutheast Asia particularly if the patient has' diabetesmellitus'9.

Studies performed in the Asia Pacific region showedthat Gram-negative bacilli other than Haemophilusinjluenzae such as Klebsiella pneumoniae are morefrequently isolated'5,17'19,20,22,23,24, The differences in themicrobiology of CAP as compared to what is reportedin the West must be taken into consideration whenselecting the appropriate antibiotics for initial empiricaltherapy of CAP in this region,

250

The microbial aetiology of severe communityacquired pneumoniaThere is no standard definition for diagnosing severeCAP. In treatment guidelines developed in the West,patients with CAP admitted to an intensive care unit(lCU) are considered as having the severe form of thedisease. However, policies for ICU admission may varyconsiderably between medical centres. Patients notadmitted to an ICU could also be having severe CAP,Host-factors such as underlying diseases, can influenceseverity of presentation of CAP. Severe CAP accountsfor approximately 5-35% of hospital-treated cases ofpneumonia with the majority of patients havingunderlying comorbidities.

The American Thoracic Society proposed definingsevere CAP on the presence of one major criteria or 2minor criteria6

• The major criteria consist of the needfor mechanical ventilation and septic shock while theminor criteria include chest radiograph showingbilateral or multilobe involvement, a PaOz/fraction ofinspired oxygen (FiOz) ratio less than 250 mm Hg andsystolic blood pressure of 90 mm Hg or less. Themicrobiology of severe CAP patients requiring ICUadmission in various studies are shown in Table II.

The microbiology of severe CAP in patients admitted tointensive care units is similar to that in other patientsadmitted to hospital with CAP. Studies conducted inthe west show that Streptococcus pneumoniae to be themost frequent causative microorganism associated withsevere CAP and it is detected in about 20% of cases.Other frequently identified pathogens are Haemophilusinfluenzae, gram-negative enteric bacilli andStaphylococcus aureus (although few of these casescould be judged as definite, i.e. confirmed bacteraemiaor isolation from pleural fluid or lung tissue); andLegionella pneumophila7,26,27. A review of nine studiesof CAP that resulted in admission to an ICU (sevenfrom Europe and one each from USA and South Africa)noted that Legionella spp were the second mostcommonly identified pathogens30, In an internationalcollaborative survey of 508 patients with culturepositive legionellosis, 92% of the isolates withserogroup 1 were L pneumophila, accounting for 84%of the total. L pneumophila serogroup 1 accounted for88% of isolates in America and Europe but for only 46%in Australia and New Zealand where L longbeachaeaccounted for 30% of cases31 . In 2 studies on severeCAP conducted in Singapore, Legionella spp was notidentified in any of the patients2S,29. However,Burkholderia pseudomallei was a common causative

Med J Malaysia Vol 60 No 2 June 2005

organism identified (Table II). MelIoidosis should beconsidered a diagnostic possibility especially if thepatient has diabetes mellitus. Pseudomonas aeruginosashould be considered in patients with underlyingstructural lung disease, for example in patients withbronchiectasis or chronic obstructive pulmonarydisease. Apart from these pathogens, other pathogensassociated with severe CAP are also frequently isolatedfrom patients with non-severe CAP.

The microbial aetiology of community acquiredpneumonia in patients treated on an ambulatorybasisThe most common pathogens identified from recentstudies of mild (Le. in ambulatory patients) CAP areStreptococcus pneumoniae, Mycoplasma pneumoniae,Chlamydia spp, and viruses (mostly influenza virus)(Table III)8,2o,26,32,33. In one study, Mycoplasmapneumoniae is the most common pathogen in patientsyounger than 50 years and without important comorbidconditions, whereas Streptococcus pneumoniae is themost common pathogen for older patients or thosewith significant underlying disease34. The high infectionrates caused by Chlamydia pneumoniae (36.7%) andMycoplasma pneumoniae (29.6%) in ambulatorypatients in the Bangkok study20 could be explained bymany factors. First, paired sera collected from most thepatients for the diagnosis of atypical pathogens in thestudy probably improved the diagnostic yield. Second,Chlamydia pneumoniae and Mycoplasma pneumoniaeoften cause a mild clinical disease, therefore patientsare more likely to be seen as outpatients. Moreover,the infection by the atypical microorganisms is morecommon among persons in a younger age group, aswas seen in the outpatients.

Initial site and antibiotic for empirical treatmentThe selection of the initial site of treatment and theinitial empirical antibiotic therapy is based on (1) riskstratification of the patient according to (a) thepresence of co-morbid conditions; (b) the severity ofthe pneumonia at presentation (based on' physicalfindings, chest radiograph changes and laboratoryfindings); and (c) the presence of identified clinical riskfactors for drug-resistant and unusual pathogens ; and(2) the local epidemiology and resistance pattern. Boththe 2001 American Thoracic Society6 and the 2000Infectious Disease Society of America3 guidelinesindicate that age alone is not a reason forhospitalization. Studies have shown that age alone, inthe absence of comorbid illness, has little impact on thebacterial etiology of CAP35-37.


Community Acquired Pneumonia - A Malaysian Perspective

Practice guidelines usually categorise CAP patientsbased on the site of treatment (outpatient, generalward, or intensive care unit), the presence of comorbidity and modifying factors (e.g., risk forpenicillin-resistant Streptococcus pneumoniae)1,2,3.4,5,6.Each patient group is assigned a list of likely pathogensand suggested antimicrobial therapy. Guidelinesadvocate the use of those antimicrobials that providecoverage of both the likely pathogens and resistantstrains.

Determining the initial site of treatmentMost patients with CAP can be safely treated asoutpatients. However, about 20% of CAP patients needhospitalization and approximately 1% require treatmentin an ICU38,39. Patients should be admitted if theyrequire close observation, intravenous antibiotics,respiratory support, or there are other concerns. Riskfactors for increased mortality associated with CAPinclude extremes of age; comorbid conditions such asmalignant disease, congestive cardiac failure, coronaryartery disease and alcoholism; vital sign abnormalities;and certain laboratory and chest radiographic findings40.The decision whether or not to admit a patient dependson the clinician's judgment which is an "art ofmedicine". However, prognostic scoring rules areavailable which provide support for this decision7,41.42. Apneumonia severity index (PSI) score or the"pneumonia prediction rule", has been developed fromstudies of the pneumonia Patient Outcomes ResearchTeam (PORT)". This prediction rule or index can beused to stratify patients to one of five risk categorieswith a score or point system based on 7 laboratory andchest radiographic parameters after an initial evaluationof three factors: age (younger than 50 years or 50 yearsor older), presence of 5 comorbid conditions(neoplastic disease, liver disease, congestive heartfailure, cerebrovascular disease and renal disease), andmental status and vital signs on admission. Thismethod has been validated for identifying patients atrisk of dying within 30 days. The risk of death is lowfor risk classes I-III (0.1-2.8%), intermediate for class IV(8.2-9.3%), and high for class V (27-31%). Apart frombeing an effective method for triaging patients, thismethod is particularly useful for identifying low-riskpatients who may be safely treated as outpatients43-46.Before calculating the severity index score, patientsshould be assessed for any pre-existing condition thatmay compromise the safety of home care, whichincludes haemodynamic instability, acute hypoxaemia,active comorbid conditions that warrant hospitaladmission, social or psychiatric problems

251


compromlsmg home care, or the inability to takemedication orall)"'7.

North American practice guidelines advocate the use ofPSI as an objective measure of risk stratification to helpdetermine the initial site of CAP treatment3,'. Easy-touse versions of the PSI are now available on handheldcomputers and the Internet: http://ursa,kcomedu/CAPcalc/default.htm, http://ncemi.org and http://www.emedhome.com/dbase,cfm.

Mortality prediction rules should be used to support,but not replace, clinician decision making, Whether ornot a patient is admitted has an effect on the extent ofdiagnostic evaluation and the choice of empiricalantibiotic therapy.

Mortality from CAPThe mortality from CAP in patients treated as outpatients is less than 1%, while that for hospitalisedpatients as a whole is 13.7%, in elderly patients 17.6%,patients with bacteraemia 19.6%, and patients admittedto ICU 36.5%40. In a recent study conducted in Malaysia(unpublished data), the overall in-hospital mortalityrate in adult patients hospitalised for CAP was 11.1%while that for patients aged 30 years or younger was0%, for patients aged 31 to 64 years was 7%, forpatients aged 65 to 80 years was 12% and for patientsaged 81 years and older was 41%24, The clinicalfeatures independently associated with an increasedrisk of dying from. CAP in these patients were age olderthan 50 years, co-existing congestive cardiac failure,multilobar pneumonia, tachycardia of 125/min or moreon admission, admission serum creatinine greater than130 [!mollL, and acute respiratory failure.

Initial empirical antibiotic therapy for CAPIn most instances, a quick microbiological diagnosis isnot possible and the microbial aetiology of CAP isunknown, As the microbial aetiology cannot bereliably predicted from the clinical, laboratory andradiological features, initial antibiotic treatment has tobe empiricaI48-'o. An awareness of the likely causativeorganism of CAP treated in different settings isimportant to allow the start of appropriate empiricalantimicrobial treatment. Table IV shows the mostcommon pathogens associated with CAP as derivedfrom collective results of various studies conducted inthe west and in the Asia Pacific region7,8,12,13,15-29,32,33.

252

North American and European guidelines3,4,6,7recommend initial empirical therapy consisting of amacrolide combined with a broad-spectrum betalactam antibiotic or monotherapy with a newerfluoroquinolone which has antipneumococcal activity("respiratory fluoquinolone") in all CAP patientsrequiring hospitalisation. Retrospective largepopulation studies have found that combinations ofbeta-Iactam antibiotics plus macrolides or monotherapywith respiratory fluoroquinolones, as initial therapy fornon-severe CAP, reduce length of stay and mortality,even when Streptococcus pneumoniae is the causativemicroorganism51-'6. These favorable outcomes may,beexplained by the role of atypical pathogens asaetiological agents of CAP, the anti-inflammatory effectsof macrolides or resistance to beta-Iactam antibiotics ofthe most important pathogens. The respiratoryfluoroquinolones can also be used to treat severeCAP'7,'8. Finch et at" showed moxifloxacin to havebetter clinical and bacteriological success whencompared with co-amoxiclav with or without amacrolide in the treatment of patients hospitalised withCAP and severe CAP, However, the development ofresistance to these respiratory fluoroquinolones hasalready been reported'9,60. Despite a high levd ofactivity against Streptococcus pneumoniae and atypicalorganisms, fluoroquinolones, are not advocated by theCenters for Disease Control (CDC) Drug-ResistantStreptoococcus pneumoniae Therapeutic WorkingGroup (DRSPTWG) because of their overextendedspectrum of coverage (inclusive of gram negativebacteria) and concern about the emergence of resistantStreptococcus pneumoniae, The use of a thirdgeneration cephalosporin and a macrolide antibioticprovides a more appropriate spectrum of coverage forCAP without carrying the added risk not only, ofresistant Streptococcus pneumoniae but also of theemergence of many resistant gram-negative organismsthat have nothing to do with the patient's pneumonia.The DRSPTWG recommends reserving the use offluoroquinolones for patients who are allergic to firstline agents, in whom first-line therapy has failed, orwho have proven resistance to penicillin2.

CAP caused by penicillin resistant StreptococcuspneumDniae (minimum inhibitory concentration lessthan 4 j.1g/ml), can still be adequately treated with betalactams at the right dosage61 , The proposed initialempirical antibiotic therapy of bacterial CAP inimmunocompetent adults according to the treatmentsetting in Malaysia is shown in Table V.


Empirical antibiotic therapy for hospitalized nonsevere community acquired pneumoniaAntibiotic therapy should be initiated promptly as thisis associated with better outcomes62,63, Antibiotictherapy should cover for Streptococcus pneumoniaeand atypical pathogens which have been shown to beprevalent as causative agents, The antibiotic optionsinclude:• A macrolide plus a penicillin or second generation

cephalosporin or a non-pseudomonal thirdgeneration cephalosporin

• A macrolide plus a B-Iactam / B-Iactamase inhibitor• Monotherapy with a fluoroquinolone with enhanced

antipneumococcal activity,

Epidemiological clues that may lead to diagnosticconsiderations are listed in Table VP, In patients withthe following co-morbidities:• COPD - antibiotic treatment should cover for

Haemophilus irifluenzae and Moraxella catarrhalis,• Bronchiectasis - antibiotic treatment should cover for

Pseudomonas aeroginosa, Examples of antibioticregimens - a B-Iactam plus an aminoglycoside or a Blactam plus ciprofloxacin

• Patients on long-term corticosteroids (doseexceeding 10 mglday of prednisolone) - shouldcover for Pseudomonas aeroginosa

Empirical antibiotic therapy for severecommunity acquired pneumoniaSince Streptococcus pneumoniaeis the most frequentlyidentified pathogen in severe CAP and Legionellapneumophila is feared for the potential severity ofinfection empirical antibiotic therapy should cover forthese two pathogens64 , The early and rapid initiation ofempiric antibiotic treatment is critical for a favorableoutcome, It should include an intravenous beta-Iactamtogether with either a macrolide or a fluoroquinolone,Modifications of this basic regimen should beconsidered in the presence of distinct comorbidconditions and risk factors for specific pathogens, Forexample, empirical therapy for Pseudomonasaeruginosa is recommended if the patient hasbronchiectasis and antibiotic cover for Burholdenapseudomallei should be considered if the patient hasdiabetes mellitus, Failure to define a pathogen inpatients with severe CAP has not been associated witha different outcome than if a pathogen is identified39,65,

Pathogen-specific therapyIf a specific pathogen can be identified within 24-72hours then continued treatment can be guided by this



information, For example, if penicillin-susceptibleStreptococcus pneumoniae is isolated, treatment shouldbe modified by selecting a narrow spectrum antibiotic(such as penicillin or amoxicillin), which will help toreduce the selective pressure for resistance, Thisinformation is often available at the time of switchingfrom parenteral to oral therapy,

Duration of antibiotic therapyMost experts recommend the total duration of antibiotictherapy should be 10-14 days, depending on theseverity of the pneumonia and the response totherapy66, An extended course of intravenousantibiotics is generally recommended for bacteraemiadue to high-risk organisms (Staphylococcus aureus orgram-negative bacilli) or suppurative complications67,Antibiotic treatment for 21 days has beenrecommended for infection due to Legionellapneumophila, The American Thoracic Societyrecommends that patients switched to oral antibioticscan be discharged on the same day if other medical andpsychosocial factors permit6, Evidence fromobservational studies suggests that there is no need toobserve patients for 24 hours after a switch fromintravenous to oral therapy67,68,

Susceptibility of Streptococcus pneumoniae tocommonly used antimicrobial agents stratified bysusceptibility to penicillinIn-vitro activities of 6 antibiotics against 92 strains ofStreptococcus pneumoniae isolated from patients inMalaysia is shown in Table VII69, The data is from astudy conducted between 1996 - 1997, Specimenswere referred by laboratories in hospitals throughoutthe country to bacteriology departments at the Institutefor Medical Research and the University of MalayaMedical Centre, 61.9% of the strains were isolated fromrespiratory tract specimens, Minimum inhibitoryconcentrations (MICs) were determined by the Etestmethod, Ten (10,9%) isolates, all from respiratory tractspecimens, were non-susceptible to penicillin (5exhibiting intermediate susceptibility and another 5resistance), The most active drug was co-amoxiclav(96,8% of isolates, including 2 that were resistant topenicillin being susceptible) followed by ceftriaxone,cefuroxime and azithromycin, As the MIC breakpointfor susceptibility to cefaclor has not beenrecommended by United States National Committee forClinical Laboratory Standards (NCCLS), the percentageof isolates susceptible to this agent could not becalculated, Of the 6 strains resistant to ceftriaxone, 5were resistant to penicillin and one exhibited

253


intermediate susceptibility. Of the 7 strains that wereresistant to cefuroxime, 5 and 2 isolates, respectively,were resistant and intermediately susceptible topenicillin. Twelve strains were resistant toazithromycin and 7 of these exhibited reducedsusceptibility to penicillin.

Penicillin-resistant Streptococcus pneumoniaeThe risk factors for penicillin-resistant Streptococcuspneumoniae (PRSP) include age younger than 2 yearsor older than 65 years, beta-lactam antibiotic treatmentwithin the past 3 months, alcoholism, multiple medicalcomorbidities, immunosuppressive illness or treatment,and exposure to a child in a day-care centreo,".Several studies showed that age older than 65 years is,by itself, a specific epidemiological risk for CAP due toPRSP, but is not an indeP1ndent risk factor for otherorganisms"'".

Under the former NCCLS criteria, Streptococcuspneumoniae infections treated with beta-lactamantibiotics to which isolates had intermediate resistancewere associated with worse clinical outcomes formeningitis but not for pneumonia. This differencemight be related to the attainable concentrations ofbeta-lactam antibiotics in cerebrospinal fluid (CSF),compared with plasma and interstitial fluid, Betalactam antibiotic concentrations in the lung interstitiaare similar to those measured simultaneously in serum,and levels in CSF are lower than those in serum73 , Thepresence of penicillin resistance itself has not beenshown to adversely affect outcome in CAP treatmentunless penicillin MIC vales are 4 mg/mL or higher3,74,

As of January 2002, the NCCLS increased the MICbreakpoints for cefotaxime and ceftriaxone. Isolates

254

with MICs of :::;1 pg/mL are now considered susceptible,those with MICs of 2 pg/mL are intermediate, and thosewith MICs of ?4 pg/mL are resistant. The newbreakpoints apply to non-meningeal Streptococcuspneumoniae infections and such infections by strainsformerly considered to be intermediately susceptibleand even some that were regarded as resistant can betreated successfully with the usual doses of beta-lactamantibiotics.

Antibiotic options in the treatment of penicillinsusceptible and penicillin-resistant Streptococcuspneumoniae are shown in Table VIII. For patientsadmitted to the general ward, high-dosebenzylpenicillin should be adequate, as long as theMICs of isolates in the local community is <2 pg/mL.Alternatively, ceftriaxone or cefotaxime (not availablein Malaysia) can be used for strains of pneumococcuswith an MIC of <2 pg/mU. If the patient has a historyof anaphylactic allergic reaction to penicillin or isallergic to cephalosporins, intravenous vancomycin oran antipneumococcal fluoroquinolone are acceptablesubstitutes. Current guidelines fOf treating PRSPpneumonia recommend choosing one of the followingantibiotics based on susceptibility testing results:ceftriaxone, cefotaxime, antipneumococcalfluoroquinolones, or, if the isolate is resistant tofluoroquinolone and cephalosporin, vancomycin4

,

Treatment guidelines cannot capture every clinicalsituation and it is therefore the responsibility of theclinician to balance the history and clinical features,assess the importance of risk factors and interpret localepidemiology and laboratory data in order to make thebest judgement for an individual patient.


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Table IV: Common causative organisms in community acquired pneumoniaaccording to site of care (severity) 1,8,12,13,15-29,32,33

Outpatient- Streptococcus pneumoniae- Mycoplasma pneumoniae- Haemophilus influenzae- Chlamydia pneumoniae- Mycobacterium tuberculosis- respiratory viruses

(Influenza A and B, adenovirus,respiratory syncytial virus,parainfluenza)

Non-ICU inpatient- Streptococcus pneumoniae- Mycoplasma pneumoniae- Chlamydia pneumoniae- Haemophilus influenzae- Klebsiella pneumoniae- Mycobacterium tuberculosis- Staphylococcus aureus- Burkholderia pseudomallei- Legionella species- aspiration (anaerobes)- respiratory viruses

ICUStreptococcus pneumoniaeLegionella speciesHaemophilus influenzaeGram-negative bacilli(Pseudomonas aerugionsa,Klebsiella pneumoniae)Staphylococcus aureusBurkholderia pseudomalleiMycobacterium tuberculosis

Table V: Proposed initial empirical antibiotic therapy of bacterial community acquiredpneumonia in immunocompetent adults according to the treatment setting

Site of treatment Common organisms Preferred antibiotic treatment optionsOut- Risk category I Risk category IPatient No co-morbidity (a) No recent antibiotic therapy(mild CAP) Should cover for • Macrolide (erythromycin 500 mg QID x 10

• Streptococcus pneumoniae days, azithromycin 500 mg 00 x 3 days, or• Mycoplasma pneumoniae c1arithromycin 500 mg BD x 10 days)• • (b) Recent antibiotic therapy

• Advanced macrolide (azithromycin orc1arithromycin) plus either (i) high doseamoxicillin or (ii) high dose amoxiicillinc1avulateOr

• Antipneumococcal f1uoroquinolone alone(moxifloxacin 400 mg 00, gatifloxacin 400mg 00 or levofloxacin 50000)

Risk category IIPresence of co-morbidity• As in risk category I• Haemophilus influenzae•


Risk category II(a) No recent antibiotic therapy• Advanced macrolide

Or• Antipneumococcal f1uoroquinolone(b) Recent antibiotic therapy• Advanced macrolide plus

either (i) high dose amoxicillin or (ii) high doseamoxiicillin-c1avulate or (iii)2nd generationcephalosporin (cefuroxime or cefprozil)Or

• Antipneumococcal f1uoroquinolone alone

259


Site of treatmentGeneralward(moderate CAP)

ICU/high dependency unit(severe CAP)

Common organismsRisk category IIIShould cover for• As in risk category I• Klebsiella pneumoniae• Haemophilus influenzae• Legionella• Staphylococcus aureus• Other Gram-negatve bacilli

- Enterobacter- Escherichia coli

• penicillin-resistantStreptococcus pneumoniae

••

Risk category IVShould cover for• As in risk category I

including PRSP• Klebsiella pneumoniae• Haemophilus influenzae• Legionella• Pseudomonas aeruginosa• •

• Staphylococcus aureus• Burkholderia pseudomallei

Preferred antibiotic treatment optionsRisk category III(a) No recent antibiotic therapy• Macrolide plus

either (i) ceftriaxone 1 gm aD or (ii) cefuroxime750 mg TDS or (iii) ~-Iactam/~-Iactamase

inhibitor (amoxicillin-c1avulanate or ampicillinsulbactam)Or

• Antipneumococcal f1uoroquinolone alone(b) Recent antibiotic therapy• same as in (a)

(regimen selected depends on nature of recentantibiotic therapy)For treatment of penicillin-resistantStreptococcus pneumoniae refer to Table VIII

Risk category IV(a) Pseudomonas infection is not an issue• (i) Ceftriaxone 1 gm BD or (ii) ~-Iactam/~

lactamase inhibitor pluseither (i) macrolide or(ii) Antipneumococcal f1uoroquinolone

(b) Pseudomonas infection is an issueEither(I) an antipseudomonal agent (piperacillin,piperacillin-tazobactam, imipenem, meropenemor cefepime) plus ciprofloxacinOr(II) An antipseudomonal agent plusaminoglycoside pluseither (i) antipneumococcal fluoroquinolone or(ii) macrolide

Cloxacillin or vancomycin• High dose ceftazidime

Or• ImipenemFor treatment of penicillin-resistant Streptococcuspneumoniae refer to Table VIII

*Mycobacterium tuberculosis should be considered in all risk categoriesOD = once daily, BD = twice daily, TDS = thrice daily, OlD = four times a day

260 Med J Malaysia Vol 60 No 2 June 2005

Table VI:


Epidemiological conditions related to specific pathogens3

ConditionAlcoholismCOPD and/or smoking

Nursing home residency

Poor dental hygieneSuspected large-volume aspirationBronchiectasisIntravenous drug abuse

Diabetes mellitus

Common encountered pathogen(s)Streptococcus pneumoniae and anaerobesStreptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis,and Legionella speciesStreptococcus pneumoniae, gram-negative bacilli, Haemophilus influenzae,Staphylococcus aureus, anaerobes and Chlamydia pneumoniaeAnaerobesAnaerobes, gram-negative enteric bacilliPseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureusStaphylococcus aureus, anaerobes, Mycobacterium tuberculosis andStreptococcus pneumoniaeMycobacterium tuberculosis, Bukholderia pseudomallei

Table VII: In-vitro activities of 6 antibiotics against 92 strains of Streptococcus pneumoniaeisolated from patients in Malaysia69

Antibiotic MICs (mg/l)MIC90 Range of MICs Susceptible isolates (%)*

Co-amoxiclav 0.03 0.016 - 8 96.8Azithromycin 1 0.016 - >256 86.9Cefaclor 1 0.25 - >256 -Ceftriazone 0.25 0.016 - 4 93.4Cefuroxime 0.25 0.016 - 16 92.5Penicillin 0.06 0.016-8 89.1

'According to the following MIC breakpoints recommended by the National Committee for Clinical laboratory Standards (NCClS):co-amoxiclav, $,0.5/0.25 mg/l; azithromycin, $,0.5 mg/l; ceftriazone, $,0.5 mg/l; cefuroxime, $,0.5 mg/l; and penicillin, $,0.06mg/l

Table VIII: Antibiotic options in the case of penicillin-resistant Streptococcus pneumoniae

Site of treatment Penicillin susceptibility Antibiotic optionOut-patient Penicillin-susceptible strains (MIC <2 fJg/mL) Oral amoxicillin, cefuroxime, cefprozil, .

macrolide, or antipneumococcalf1uoroquinolone (moxifloxacin, gatifloxacin orlevofloxacin)

General ward Intravenous benzylpenicillin 2 mega units 4hourly,75 ampicillin 1 g 6 hourly, orceftriaxone 1 ~ once daily

ICU Penicillin-resistant Vancomycin, antipneumococcalstrains (MIC;::2 fJg/mL) f1uoroquinolone or linezolid

(high dose amoxicillin 3 g/day should beeffective for strains with MIC 2-4 fJg/mL)76

......

Med J Malaysia Vol 60 No 2 June 2005 261


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265


MCQs on Community Acquired Pneumonia - A Malaysian Perspective

1. The following statements on the microbial aetiology of community acquired pneumonia are true:a. In 'real world' practice the aetiological microorganism is identified in more than 50% of cases.b. Streptococcus pneumoniae is the most commonly identified causative organism.c. Mycoplasma pneumoniae is more frequently identified in younger patients without comorbitiy.d. Burkholderia pseudomallei should be considered a possible causative organism in rural Southeast Asia

particularly if the patient has diabetes mellitus.e. There is a low incidence of Legionella pneumonia in studies conducted in Asian countries.

2. The following statements on community acquired pneumonia are true:a. Infection due to Mycobacterium tuberculosis may present as community acquired pneumonia in Malaysia.b. Culture of expectorated sputum is a reliable test for identification of the causative organism.c. Recent findings show that less than 5% of Haemophilus influenzae isolates in Malaysia are ~-lactamase

producing.d. Blood cultures are positive in 40% or more of cases.e. Some Streptococcus pneumoniae strains are resistant to penicillins through the production of ~-lactamase.

3. The following f"mdings in patients with pneumonia indicate that the stated organism is def"mitely theaetiological agent:

a. Blood culture positive for Streptococcus pneumoniae.b. Presence of Legionella pneumophila serogroup 1 antigen in the urine.c. Sputum culture yields moderate growth of Haemophilus influenzae.d. A fourfold rise in IgM antibody titre to Mycoplasma pneumoniae.e. Isolation of Pseudomonas aeruginosa from pleural fluid collected from chest drain.

4. The following statements on the treatment of community acquired pneumonia are true:a. The newer fluoroquinolones are effective against Streptococcus pneumoniae.b. Antipseudomonal third generation cephalosporins are the antibiotic of choice in the treatment of most cases of

community acquired pneumonia.c. The antibiotic of choice in the empirical treatment of Mycoplasma pneumonia is a fluoroquinolone.d. Pneumonia due to aspiration of oropharyngeal contents can be effectively treated with penicillin.e. Metronidazole provides excellent coverage for Gram-positive anaerobes.

5. The following statements on the outcome of community acquired pneumonia treatment are true:a. Antibiotic therapy that covers for both Streptococcuspneumoniae and atypical pathogens in hospitalised patients

results in more favourable outcomes.b. Mortality is higher in elderly patients.c. High-level penicillin resistance is associated with increased mortality in Streptococcus pneumoniae pneumoniad. Failure to identify a pathogen in patients with severe CAP has been associated with a worse outcome than if a

pathogen is identified.e. The implementation of treatment guidelines has been shown to reduce mortality and health care costs.

266 Med J Malaysia Vol 60 No 2 June 2005

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Community Acquired Pneumonia - A Malaysian Perspective · PDF fileCONTINUING MEDICAL EDUCATION Community Acquired Pneumonia - AMalaysian Perspective C K Liam, FRCP Department ofMedicine,