The Philippine Clinical Practice Guidelines on the Diagnosis, Empiric Management and Prevention of Community-Acquired Pneumonia in Immunocompetent Adults:

A Quick Reference Guide for Clinicians

Report of the Task Force on Community-acquired Pneumonia 1998
(*Editors note: The summaries of evidence were omitted for this quick reference. The summaries of evidences are in the complete guideline pamphlet available at the PSMID office.)

INTRODUCTION
Pneumonia is the fourth leading cause of morbidity and the third leading cause of mortality in Filipinos based on the 1994 Philippines Health Statistics. This clinical practice guideline on community-acquired immunocompetent adults has been drafted to provide the clinician with practical approaches in the resolution of important issues on the diagnosis, management, and prevention of CAP in adult patients. This consensus is a collaborative undertaking of various medical specialty societies concerned with the care of patients with CAP such as the Philippine Society for Microbiology and Infectious Diseases (PSMID), Philippine College of Chest Physicians (PCCP), American College of Chest Physicians Philippines Chapter (ACCP-PC), Philippine Academy of Family Physicians (PAFP), Department of Health (DOH), Philippine College of Radiology (PCR), and the Philippine College of Emergency Medicine and Acute Care (PCEMAC). Inputs from other stakeholders and end-users were also taken into account through discussions and supplemented by questionnaires using the modified Delphi technique. The recommendations have been based on evidence derived from a critical review of the literature. A systematic search of the literature using computer-based search strategies was first undertaken and relevant articles, including local data, when available, were selected. A Medline search of the medical literature was conducted using combinations of query terms which included community-acquired pneumonia, signs, symptoms, chest radiography, microbiology, sputum Grams stain and culture, diagnosis, hospitalization, risk factors, treatment, mortality, outcome, prognosis, prevention, pneumococcal and influenza vaccines. Medical specialists in the field of infectious disease, pulmonary, family medicine, and general practitioners involved in the care of CAP on the outpatient and hospital settings are the targeted physicians. [Phil J Microbiol Infect Dis 2002; 31(2):74-84] Key Words: Community acquired pneumonia, guideline

1. Which patient has community-acquired pneumonia (CAP)? Pneumonia is a lower respiratory track infection presenting 24 hours to less than 2 weeks which when acquired in the community is referred to as community-acquired pneumonia (CAP). A patient with cough who has abnormal vital signs of tachypnea (RR >20/min.), tachycardia (CR > 100/minute), and fever (T > 37.8oC) ) with at least one abnormal chest finding of diminished breath sounds, rhonchi, crackles or wheezes probably has pneumonia. However, these clinical findings are not sufficiently accurate in diagnosing pneumonia. A radiographic chest examination showing new infiltrates that has no clear alternative cause such as lung cancer or pulmonary edema is required to confirm the diagnosis (Grade A). In situations where chest radiography may not be available, clinical prediction rules may be utilized to help physicians identify patients who may have pneumonia [(Grade B) Table 1]. 2. What other information can be derived from the chest x-ray? In addition to confirming the diagnosis of pneumonia, an initial chest radiographic examination is essential in assessing the severity of disease, presence of complication, and for prognostication. Finding of bilateral or multilobar involvement, progression of infiltrates within 24 hours, pleural effusion, and lung abscess are suggestive of severe disease, poor prognosis and indicate the need for hospital admission (Table 2).

Table 1. Accuracy of predicting pneumonia by physicians clinical judgment, Heckerling et al. Score, and Gennis et al. Rule Physicians clinical judgement History Physical findings Heckerling et al Score (threshold was 2 points) Temperature > 37.8oC Pulse > 100/min Rales Decreased breath sounds Absence of asthma 68% Gennis et al Rule (threshold was 1 point) Temperature > 37.8oC Pulse > 100/min Respiration > 20/min 76%

Decision basis Variables

Accuracy in predicting pneumonia

60%

Table 2. Chest radiographic findings which may predict a complicated course Chest radiographic findings Multilobar radiographic pulmonary infiltrate Bilateral pleural effusion Odds ratio 3.1 2.8 95% C.I. 1.9 - 5.1 1.4 - 5.8

Chest radiography may also suggest possible etiologies and help in differentiating pneumonia from other conditions that may mimic it (Grade A). 3. What microbiologic studies are necessary in CAP? The establishment of an etiologic agent is ideal as a diagnostic standard. However, despite adequate studies using good microbiologic techniques, an identifiable pathogen is found in only 40-50% of cases of CAP. Sputum gram stain and culture is therefore not recommended for routine use particularly in patients who do not require hospitalization where the etiology is predictable (Grade B). However, for hospitalized patients with severe disease, there are more pathogens to consider. In these patients, blood cultures at least on 2 separate samplings, are highly recommended. Although of low sensitivity, a positive blood culture is specific and is considered as the gold standard in the etiologic diagnosis of pneumonia. Gram stain and cultures of appropriate pulmonary secretions in addition to a blood culture should be part of the initial workup of patients hospitalized for severe pneumonia. When available, antigen detection for Legionella particularly for elderly patients is also recommended (Grade A). Invasive procedures such as transtracheal aspirate, lung tap, bronchoalveolar lavage, and protected specimen brush to obtain respiratory secretions for microbiologic studies are reserved for non-resolving pneumonia, immunocompromised patients or when anaerobic disease is considered (Grade B). 4. Which patient will need hospital admission? The physician's decision to hospitalize a patient or not can be guided by a number of prognostic indicators for a complicated course and mortality (Table 3). On the basis of several prognostic factors, patients with CAP can be classified into four risk categories to help determine the need for hospitalization (Algorithm). The category of CAP at initial assessment may change during the course of treatment and alter the physician's initial decision. Adult patients with CAP who are < 65 years of age with stable vital signs (RR < 30 breaths/ minute, diastolic blood pressure 60 mmHg and systolic blood pressure 90 mmHg, pulse < 125 beats/minute, and temperature < 40oC) and no co-morbid condition are associated with low morbidity and mortality rate of < 1% and are thus categorized as Minimal Risk CAP (I). They are considered suitable for outpatient care (Grade A).

Table 3. Independent predictors of complicated course in patients with CAP Predictor Age > 65 Years Co-morbid illness Temperature > 38C Immunosuppressive therapy* High-risk etiology *Recent systemic steroid use or cancer chemotherapy Odds ratio 2.7 3.2 4.1 12 23.3 95% Confidence Interval 1.4 - 4.1 1.4 - 7.5 1.8 - 9.2 1.1 - 132.9 2.7 - 200.7

Those patients with stable (controlled DM, neoplastic disease in remission, stable neurologic disease, class 1 CHF, compensated COPD and chronic liver disease, and renal failure not on dialysis) co-morbid conditions such as diabetes mellitus (DM), neoplastic disease, neurologic disease, congestive heart failure, immunosuppressive therapy (Grade A), renal insufficiency (Grade B), chronic obstructive pulmonary disease (COPD), chronic liver disease, or chronic alcohol abuse (Grade C), are associated with mortality rate of < 5% and are thus

categorized as Low Risk CAP (II). They may he treated as outpatients if there is a reasonable assurance for follow-up (Grade C). However, they should he considered for hospitalization in the event that the co-morbid condition is aggravated by or aggravating the pneumonia (Grade A). Patients with CAP who are > 65 years shall be hospitalized regardless of clinical condition (Grade A). Patients, regardless of age, with any one of the following physical findings: RR > 30 breaths/ minute, pulse rate of >125 beats/minute, or temperature 35oC or 40oC; those with radio-graphic findings of bilateral or multi-lobar involvement, progress-ion of lesion to 50% of initial finding within 24 hours, pleural effusion, abscess; those with suspected aspiration; and those with extrapulmonary evidence of sepsis are associated with a complicated outcome and higher mortality rate of ~ 21% and are thus categorized as Moderate Risk CAP (III). These patients need to he hospitalized for parenteral therapy (Grade A). Patients with impending or frank respiratory failure (i.e., hypoxemia with PaCO2, < 60 mmHg or acute hypercapnea with PaCO2 > 50 mmHg) or hemodynamic alterations and hypoperfusion (i.e., altered mental state, DBP < 60 mmHg or SBP < 90 mmHg, or urine output < 30 ml/hour), are associated with mortality rate of ~ 36.5% (Table 4) thus categorized as High Risk CAP (IV), warranting admission in the intensive care unit (Grade A).
Table 4. Physical and laboratory findings which may predict mortality in CAP Physical findings Altered mental state RR breaths/min DBP < 60 mmHg SBP 100 mmHg Laboratory findings Bacteremia BUN > 7 mmol/L WBC < 4 or > 30x109/L or ANC* < 1x109/L *Absolute neutrophil count Odds ratio 2.3 3.16 3.67 4.8 2.8 5.2 2.5 95% Confidence Interval 1.6 3.3 1.07 9.3 1.23 10.9 2.8 8.3 2.3 3.6 2.4 10.9 1.6 3.7

5. What initial antibiotics are recommended for the empiric treatment of pneumonia? Empiric antibiotic therapy is based on the likely etiology of the pneumonia (Table 5). In young adult patients with mild to moderate pneumonia who are treated as outpatient, S. pneumoniae and H. influenzae are the predominant etiologic agents responsible for more than half of cases where a pathogen is identified. Amoxicillin is considered to be the standard regimen for outpatient care. In addition, atypical pathogens including M. pneumoniae and C. pneumoniae have been demonstrated. Alternative regimens are extended macrolides (clarithromycin) or azalides or cotrimoxazole in areas of limited resources (Grade A). In patients with co-morbid illness, in addition to the above potential pathogens, Gramnegative bacilli have to be considered. For such patients, cotrimoxazole or beta-lactams, which have efficacy against these additional pathogens, are recommended. For out-patient care, orally administered drugs are ideal and these include co-amoxiclav or sultamicillin or the secondgeneration oral cephalosporins (Grade A). In elderly patients and those with severe disease, S. pneumoniae and Legionella sp. are important etiologic considerations as well as gram-negative bacilli including anaerobes when the risk of aspiration is great. A parenteral beta-lactam with anaerobic coverage is recommended including co-amoxiclav or ampicillin/sulbactam or cefoxitin or ceftizoxime. Other 2nd generation cephalosporins (cefamandole, cefuroxime, or cefotiam) or ceftriaxone or cefotaxime may be used if aspiration is not likely (Grade A). Parenteral therapy with erythromycin or alternatively, oral macrolides may be given if Legionella is suspected.

Table 5. Potential pathogens and empiric antimicrobial therapy Minimal Risk CAP (I) S. pneumoniae H. influenzae C. pneumoniae M. pneumoniae Low Risk CAP (II) S. pneumoniae H. influenzae C. pneumoniae M. pneumoniae M. catarrhalis Gram-negative bacilli (enteric) Cotrimoxazole Or Co-amoxiclav Or Sultamicillin Or 2nd gen. oral cephalosporins Or extended macrolide Moderate Risk CAP (III) S. pneumoniae H. influenzae Legionella C. pneumoniae M. pneumoniae Gram-negative bacilli Anaerobes IV beta-lactams with/without anaerobic coverage +/Erythromycin IV* or levofloxacin alone High Risk CAP (IV) S. pneumoniae H. influenzae Legionella C. pneumoniae M pneumoniae S. aureus Gram-negative bacilli P. aeruginosa anti-pseudomonal beta-lactams +/aminoglycoside or Ciprofloxacin + Erythromycin IV

Potential Pathogens

Empiric therapy

Amoxicillin Or extended macrolide Or Cotrimoxazole

In those with severe disease with evidence of septic shock and/or respiratory failure, broadspectrum coverage to include P. aeruginosa and S. aureus, pending results of bacteriologic studies, is recommended as these pathogens are associated with increased mortality. The recommended agents include beta-lactams with antipseudomonal activity such as ceftazidime, cefoperazone, carbapenems (imipenem or meropenem) or piperacillin-tazobactam or 4th generation cephalosporins (cefepime or cefpirome) with or without aminoglycosides, in combination with empiric parenteral erythromycin if Legionella is strongly suspected (Grade A). Alternative therapy for Legionella includes IV azithromycin, IV levofloxacin or IV ciprofloxacin based on in-vitro and animal studies; no RCTs are available (Grade C). If clinically suspected, specific anti-staphylococcal agents such as oxacillin may be given in cases of lung abscesses, pneumatocoele and pneumothorax. Antianaerobic coverage with clindamycin or metronidazole is recommended in cases of aspiration, depressed sensorium or seizure episodes (Grade). Some beta-lactams such as carbapenems and piperacillin-tazobactam provide broadspectrum coverage including staphylococcus and anaerobes. The recommended dosages of these antibiotics in adults weighing 50-60 kg, with normal renal and liver function are shown in Table 6. The recommended empiric initial antibiotic therapy should subsequently be modified based on the isolated pathogen (Table 7). If microbiologic data is available, the revised treatment should be pathogen-directed based on antimicrobial susceptibility test (Table 8). 6. How do we assess response to initial therapy? Most patients with uncomplicated bacterial pneumonia will respond to treatment within at least 24-72 hours and patients should be reassessed after 72 hours of initiating therapy. A patient is considered to have responded to treatment if fever declines within 72 hours, temperature normalizes within 5 days, and respiratory signs, particularly tachypnea, return to normal. A follow up chest x-ray is not necessary to confirm that the infiltrate has cleared for patients with minimal risk and low risk CAP since the lesions may persist for weeks and findings will not influence the management In hospitalized patients, streamlining initial empiric broad

spectrum parenteral therapy to a single narrow spectrum parenteral agent or an oral agent, based on available laboratory data, is recommended as early as 72 hours. Switch therapy to an oral agent if there is less cough and resolution of respiratory distress, if patient is afebrile for more than 24 hours, if the etiology is not a high risk (virulent/resistant) pathogen, if there is no unstable co-morbid condition or life-threatening complication such as MI, CHF, complete heart block, new atrial fibrillation, supraventricular tachycardia, etc., if there is no obvious reason for continued hospitalization such as hypotension, acute mental changes, BUN: Creatinine of >10:1, hypoxemia, metabolic acidosis, etc., will allow discharge from hospital as early as the 4th day of hospitalization and will lead to cost-savings (Table 9). Oral agents with good bioavailability, with a spectrum of activity approximating parenteral agents are shown in Table 10.
Table 6. Usual recommended dosages of antibiotics in adults, 50-60 kg body weight, with normal liver and renal function Antibiotic Amoxicillin PO Azithromycin PO Clarithromycin PO Cotrimoxazole PO Co-amoxiclav PO Sultamicillin PO Erythromycin IV Co-amoxiclav IV Sulbactam/Amp IV Cefamandole IV Cefotaxime IV Erythromycin IV Ciprofloxacin IV Cefoperazone IV Ceftazidime IV Imipenem IV Meropenem IV Pip/Tazobactam IV Antibiotic Minimal Risk CAP 250 500 mg TID Dirithromycin PO 500 mg OD x 3 days Roxithromycin PO 250-500 mg BID Cotrimoxazole PO Low Risk CAP 160/800 mg BID Cefuroxime 625 mg 1 g BID Cefaclor PO 375 750 mg BID Cefprozil PO Moderate Risk CAP 1gq6h Cefotiam IV 1.2 g q 8 h Cefuroxime IV 0.75 1.5 g q 8 h Ceftizoxime IV 0.5 2.0 g q 8-12 h Cefoxitin IV 0.5 2.0 g q 8-12 h Ceftriaxone IV Levofloxacin IV High Risk CAP 1gq6h Cefepime IV 200-400 mg q 12 h Cefpirome IV 1 2 g q 6-12 h Amikacin IV 12gq8h Netilmycin IV 500 mg q 6 h Oxacillin IV 1gq8h Clindamycin IV 2.25-4.5 g q 6-8 h Metronidazole IV Dosage Dosage 500 mg OD 150 mg BID 160/800 mg BID PO 250-500 mg BID 250-500 mg TID 5 00 mg BID 0.5 1 g q 6-12 h 0.75 1.5 g q 8 h 1 g q 12 h 1-2 g q 8 h 1-2 g q 12 h 0.5 g OD 1 2 g q 12 h 1 g q 12 h 15 mg/kg/24 h 7 mg/kg/24 h 0.5 2 g q 4-6 h 300 600 mg q 6-8 h 500 mg q 8 h

Table 7. Rank order of etiologic agents of community-acquired pneumonia Countries Phil Denmark Spain Spain France Australia USA Spain Phil Canada #1 S. pneumoniae S. pneumoniae S. pneumoniae Coxiella burnetti S. pneumoniae S. pneumoniae S. pneumoniae S. pneumoniae Non-grp. B H. influenzae S. pneumoniae #2 M. tuberculosis H. influenzae H. influenzae M. pneumoniae H. influenzae Viruses H. influenzae L. pneumophilia L. pneumophilia C. psitacci #3 Chlamydia spp M. pneumoniae G (-) bacilli S. pneumoniae G (-) bacilli H. influenzae L. pneumophilia H. influenzae S. pneumoniae M. pneumoniae #4 L. pneumophilia L. pneumophilia L. pneumophilia G (-) bacilli S. aureus G (-) bacilli Chlamydia spp K. pneumoniae H. influenzae Influenza A #5 M. pneumoniae Chlamydia spp M. pneumoniae L. pneumophilia L. pneumophilia M. pneumoniae G (-) bacilli S. marcescens K. pneumoniae Coxiella burnetti

Based on etiology, the duration of treatment is 5-7 days for bacterial pneumonia, except for enteric gram-negative pathogens, S. aureus and P. aeruginosa, where treatment should be prolonged to 10-14 days, 10-14 days for Mycoplasma and Chlamydia, and 14-21 days for

Legionella. A 3-day course of oral therapy for minimal and low risk CAP is possible with new agents such as the azalides which possess pharmacodynamic characteristics prolonging their duration of effect (Table 11).
Table 8. Resistance rates of S. pneumoniae and H. influenzae isolated from Filipino patients with communityacquired pneumonia S. pneumoniae 47 2 0 0 0 0 H. influenzae 55 0 0 0 0 -

No. of cases (n) Penicillin G Ampicillin Cotrimoxazole Chloramphenicol Tetracycline Erythromycin Azithromycin Ceftriaxone

209 0.5 1.0 0.5 7.7 0

43 6.9 3 4.8 9.5 2.7 -

42 2.4 0 0 0 98 -

93 3.3 5 4.3 13.9 -

Table 9. Streamlining of empirical antibiotic therapy A switch of oral antibiotic therapy is possible after 72 hours following initiation of empirical treatment. This will shorten hospital stay as they could be discharged after the 4th hospital day and lead to cost-savings if: 1. There is less cough and resolution of respiratory distress (normalization of RR). 2. The patient is afebrile for > 24 hours. 3. The etiology is not a high-risk (virulent/resistant) pathogen. 4. There is no unstable co-morbid condition or life-threatening complication such as MI, CHF, complete heart block, new atrial fibrillation, supraventricular tachycardia, etc. 5. There is no obvious reason for continued hospitalization such as hypotension, acute mental changes, BUN:CR of > 10: 1, hypoxemia, metabolic acidosis, etc. Table 10. Oral agents with good bioavailability and convenient dosing schedule for switch therapy Second and third generation cephalosporins: Cefuroxime axetil, Cefaclor, Cefprozil, Cefixime, Cefdinir, Cefetamet Ceftibuten New macrolides: Clarithromycin, Azithromycin, Dirithromycin Fluoroquinolones Ciprofloxacin, Ofloxacin, Levofloxacin Table 11. Duration of antibiotic use based on etiology Etiologic Agent Most bacterial pneumonia except enteric gram (-) pathogens, S. aureus, and P. aeruginosa Enteric gram (-) pathogens, S. aureus, and P. aeruginosa Mycoplasma and Chlamydia Legionella Duration of therapy (days) 57 3 (Azalides) 10 - 14 10 - 14 14 - 21

In patients initially seen after antibiotic therapy has already been initiated, if the choice is among the recommended options and the dosage is correct and the patient has not improved after 72 hours, change the antibiotic. If the dosage of the antibiotic is inadequate, correct the dosage and continue the drug. If there is no response to treatment, reassess the patient clinically, radiologically, and bacteriological. Assess the patient for possible co-infection in other sites. A follow-up chest xray in these patients is useful to determine possible complications of progress-ion of disease, pleural effusion, empyema, pneumothorax, cavitation, and extension to previously uninvolved

lobes, pulmonary edema or ARDS. Assess bacteriologic studies to determine resistance to the antibiotic being given or the presence of other pathogens such as M. tuberculosis or fungi, and revise treatment accordingly. In the elderly, S. pneumoniae and L. pneumophilia may be causes of slowly resolving pneumonia. Severe disease warrants close clinical and hemodynamic monitoring to determine the need for specialized ventilatory support. These patients may require modification of therapy based on available bacteriologic data or longer treatment based on clinical parameters (Grade A). 7. How do we prevent pneumonia? The prevention of pneumonia with the use of vaccine should be particularly effective in those at greatest risk of pneumonia for the strategy to the cost-effective. The 23-valent pneumococcal vaccine is recommended for any of the following high risk patients: a) persons >65 years (Grade B); b) persons with increased risk of pneumococcal disease or its complication due to chronic illness, such as cardiovascular disease (Grade A), COPD (Grade A), diabetes mellitus (Grade B), alcoholism (Grade A), chronic liver disease (Grade C); c) patients with functional or anatomic asplenia (Grade C); d) persons living in environments in which the risk for invasive pneumococcal disease or its complications is increased, such as nursing homes and chronic care facilities (Grade A); and e) immunocompromised persons (Grade A) who are at high risk for pneumococcal infection. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (Atlanta, Georgia) recommends more extensive use of the pneumococcal vaccine among high-risk groups. The 23-valent form contains the capsular polysaccharides of 23 pneumococcal serotypes, which account for about 90% of pneumococcal infectious in the US. In the Philippines, surveillance data of invasive isolates of S. pneumoniae among children with bacterial meningitis showed that 92% were vaccine types. The pneumococcal vaccine may he useful despite the lack of data on important serotypes among Filipino adults, but the applicability of evidence from foreign published literature needs to he studied further. The influenza vaccine reduces the risk of pneumonia in high-risk persons during an influenza epide-mic if the vaccine strain is identical or similar to the epidemic strain. Influenza vaccination may be given annually to any of the following: a) persons > 65 years (Grade B), b) residents of nursing homes and other chronic care facilities that house persons who have chronic medical conditions, c) persons with chronic pulmonary or cardiovascular disorders, and d) patients who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases, renal dysfunction, hemoglobinopathies, or immunosuppression (Grade C). The ACIP suggests that yearly vaccination of high-risk persons before the influenza season is the most effective strategy for reducing the impact of influenza. The virus strains selected for each year's vaccine are based on the antigenic characteristics of circulating strains. The vaccine, which is offered to target groups from September to November, contains three virus strains representing the strains that are likely to circulate in the upcoming winter. In the Philippines, influenza is characterized by several epidemics each year, with two main peaks. A large peak occurs during the rainy season from June to September, particularly from July to August. A smaller peak is noted during the months of December to January. Because of the lack of local data on prevailing strains and the more disseminated pattern of influenza, it is difficult to assess the potential impact of the influenza vaccine among high risk Filipino patients. There is no data from the published literature on the use of lyophilized bacterial lysate or bronchovaxom in the prevention of pneumonia. REFERENCES

Albaum N, Hill L, Murphy M, et al. Interobserver reliability of chest radiograph in community-acquired pneumonia. Chest 1996; 110:343-350. Almirral L, Valls F, Catalan F, Balazo X. Incidence of community acquired pneumonia and Chlamydia pneumoniae infection: A prospective multicenter study. Eur Respir J. 1993; 6:14-18. American Thoracic Society. Guidelines for the initial management of adults with community-acquired pneumonia: diagnosis, assessment of severity, and initial antimicrobial therapy. Am Rev Respir Dis 1993; 148:1418-1426. Barlett JG, Breiman RF, Mandell LA, File TM. Community acquired pneumonia in adults: Guidelines for management. Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 1998; 26:811-838. Bates J, Campbell G, Barron A, et al. Microbial etiology of acute pneumonia in hospitalized patients. Chest. 1992; 101(4):1005-1012. Bernas GA, Galvez BB. Community-acquired pneumonia: etiology, clinical profile and outcome. Phil J of Chest Dis 1997; 5(1):31-39. Boerner D, Zwadyk P. The value of the sputum Grams stain in community acquired pneumonia. JAMA 1982; 247 (5):642-645. British Thoracic Society, London. Guidelines for the management of community acquired pneumonia in adults admitted to hospital. Brit J Hosp Med 1993; 346-350. Butler JC, Breiman RF, Campbell JF, Lipman HB, Broone CV, Facklam RR. Pneumococcal polysaccharide vaccine efficacy. JAMA 1993; 270:1826-1831. Campbell H, Forgie IM, Lloyd-Evans N, Byass P, ONeill KP, Greenwood BM. Trial of cotrimoxazole vs. procaine penicillin in treatment of community-acquired pneumonia. Chest, 1988; 92(1):1184-1186. Capeding MRZ, Sombrero LT, Lucero MG, Saniel MC. Serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates in Filipino children. J Infect Dis 1994; 169:479-480. Carlos C, Mendoza M. Prevalence of drug resistance among pneumococci in Metro Manila hospitals 1996-1997. (For publication). Chan V. Epidemiological data on influenza in the Philippines. First International Symposium on Adult Immunization in Asia: Prevention of Influenza and Pneumococcal Infections. Hanoi, Socialist Republic of Vietnam 1998, April 2022:3537. Cunha BA, Ortega AM. Atypical pneumonia: extra pulmonary clues guide the way to diagnosis. Postgrad Med 1996; 99(1):123-132. Davidson M, Tempest B, Palmer D. Bacteriologic diagnosis of acute pneumonia. Comparison of sputum, transtracheal aspirates and lung aspirates. JAMA 1976; 235 (2): 158-163. Edelstein P. Antimicrobial chemotherapy for Legionnaires disease: A Review. Clin Inf Dis 1995; 21:S265-S276. Edelstein PH, Edelstein MA, Ren J, Polzer R, Gladue R. Activity of trovafloxacin against Legionella isolates: in vitro activity, intracellular accumulation and killing in macrophages, and pharmacokinetics and treatment of guinea pigs with L. pneumophila pneumonia. Antimicrob Agents Chemother 1996; 40:314-319. Edelstein PH. Antimicrobial chemotherapy for legionnaires disease: time for a change. Ann Intern Med 1998; 129(4):328-330. Emerman CL, Damson N, Spore T, et al. Comparison of physician judgment and decision aids for ordering chest radiographs for pneumonia in out patients. Ann of Emerg Med 1991; 20(11):1215-1219. Fang G, Fine M, Orloff J, et al. New and emerging etiologies for community acquired pneumonia with implications for therapy. A prospective multicenter study of 359 cases. Medicine 1990; 69 (5):307-16. Farr BM, Johnston BL, Cob DK, et al. Preventing pneumococcal bacteremia in patients at risk. Arch Intern Med 1995; 155:23362340. Farr BM, Sloman AJ,Fisch MJ. Predicting death in patients hospitalized for community-acquired pneumonia. Ann Intern Med 1991;115(6):428-436. Finch RG and Woodhead MA. Practical considerations and guidelines for the management of community-acquired pneumonia. Drugs 1998; 55(1):31-45. Fine MJ, Smith MA, Carson CA, et al. Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis. JAMA 1996; 275(2):134-140. Fine MJ. Hospitalization decisions in patients with community-acquired pneumonia: a prospective cohort study. Am J Med 1990; 89:713-721. Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1991; 115(6):243-250. Fine MJ, Smith M, Carson C, et al. Efficacy of pneumococcal vaccination in adults. A meta-analysis of randomized controlled trials. Arch Intern Med 1994; 26:154(23): 2666-2677. Gennis P, Gallagher J, Favlo C, Baker S, Than W. Clinical criteria for the detection of pneumonia in adults: Guidelines for ordering chest roentgenograms in the emergency department. J of Emerg Med 1989; 7(3):263-268. Gleckman R, DeVittaJ, Hibert D, et al. Sputum Grams stain assessment in community acquired bacteremic pneumonia. J Clin Micro. 1988; 26(3):846-849. Gross P, Hermogenes A, Sacks H, Lau J, Levandowski R. The efficacy of influenza vaccine in elderly persons: A meta-analysis and review of literature. Ann Intern Med 1995; 123(7); 518-527. Heckerling PS, Tape TG, Wigton RS, et al. Clinical prediction rule of pulmonary infiltrates. Ann Int Med 1990; 113:664-670. Hitt CM, Nightingale CH, Quintiliani R, Nicolau DP. Streamlining antimicrobial therapy for lower respiratory tract infections. Clin. Infect Dis 1997; 24(Suppl 2): S213-S217. Houston MS, Silverstein MD, Suman VJ. Risk factors for 30-day mortality in elderly patients with lower respiratory tract infection. Arch Intern Med 1998; 21(3): 276-380. Keeley DJ, Nkrumah FK, Kapuyanyika C. Randomized trial of suflamethoxazole and trimethoprim vs. procaine penicillin. Bull of World Health Organization 1990; 68(2):185-192. Koivula I, Sten M, Leinonen M, Makela PH. Clinical efficacy of pneumococcal vaccine in the elderly: A randomized, single-blind population-based trial. Am J Med 1997; 103(4):281-290. Levy M, Dreoer F, Brion N, Leturdu F, Carbon C. Community-acquired pneumonia. Chest, 1998; 92(1):43-48. Lim I, Shaw D, Stanley D, Lumb R, McLeenan G. A prospective study of the aetiology of community acquired pneumonia. Med J of Aus. 1989; 151:87-91. Manaloto C, Mendoza S. Escamilla J, Fernando M, Buck R, Ranoa C. Acute pneumonia in San Lazaro Hospital. Phil J Microbiol Infect Dis 1985; 14(1):23-26.

Mandell LA, Niedermann M. The Canadian community-acquired pneumonia in adults: A conference report. Can Infect Dis 1993; 4(1):25-28. Marrie T, Peeling R, Fine M, Singer D, Coley C, Kapoor W. Ambulatory patients with community-acquired pneumonia. The frequency of atypical agents and clinical course. Am J Med. 1996; 101:508-515. Marrie TJ, Durant H, Yates L. Community-acquired pneumonia requiring hospitalization: 5-year prospective study. Rev Infect Dis 1989; 11(4):586-599. Melbye J, Straume B, Aasebo U, Dale K. Diagnosis of pneumonia in adults in general practice. Scand J Prim Health Care; 10:126132. Metlay, JP, Kapoor WN, Fine MJ. Does this patient have community-acquired pneumonia? JAMA 1997; 278(17);1440-1445. Metlay JP, Schulz R, Li YH, et al. Influence of Age on Symptoms at presentation in patients with Community-Acquired Pneumonia. Arch Intern Med 1997 July; 157:1453-1459. Minogue MF, Coley CM, Fine MJ, Marrie TJ, Kapoor WN, Singer DE. Patients hospitalized after initial outpatient treatment for community-acquired pneumonia. Ann Emerg Med 1998; 21(3):276-380. Mittl RL Jr., Schwab RI, Duchin JS, Goih JB, Albeida. Radiographic resolution to commu-nity-acquired pneumonia. Am J Respir Crit Care Med 1994;149:630-635. Moine P. Vercken J, Chevret S. Shastang C, Gajdos P. Severe community-acquired pneumonia. Etiology, epidemiology and prognostic factors. French study group for community-acquired pneumonia in the ICU. Chest 1994;105(5):1486-1495. Mundy LM, Oldah D, Auwaerten PG, et al. Implications for macrolide treatment in community-acquired pneumonia. Chest 1998; 113(5):1201-1206. Murray P, Washington J. Microscopic and bacterio-logic analysis of expectorated sputum. Mayo Clin. Proc. 1975; 50:339-444. Myburgh J, Nagel GL, Perschel E. The efficacy and tolerance of a three-day course of azithromycin in the treatment of communityacquired pneumonia. J. Antimicrob Chemother 1993; 31(Suppl E):163-170. Ortqvist A, Hedlund J, Burman L, et al, and Swedish Pneumococcal Vaccination Study Group. Randomized trial of 23-valent pneumococcal capsular polysaccharide vaccine in the preven-tion of pneumonia in middle-aged and elderly people. Lancet 1998; 351:399-403. Ostergaard L, Andersen P. Etiology of community-acquired pneumonia. Evaluation by trans-tracheal aspiration, blood culture or serology. Chest 1993; 104:1400-1407. Pachon J, Prados MD, Capote F, Cuello JA, Garnacho J, Verano A. Severe community-acquired pneumonia. Etiology, prognosis, and treatment. Am Rev Respir Dis 1990; 142:369373. Pareja A, Bernal C, Leyva A, Piedrola G, Marvoto C. Etiologic study of patients with CAP. Chest 1992; 101(5):1207-1210. Prevention and Control of Influenza: Recommenda tions of the Advisory Committee on Immunization Practices (ACIP). MMWR April 25; 46(RR9):1-25. Prevention of pneumococcal disease: Recommen-dations of the Advisory Committee on Immu-nization Practices (ACIP). MMWR 1997; 4;46(RR8): 1-24. Ramirez JA, Srinath L, Ahkee S, Huang A, Raff M. Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia.Arch Intern Med 1995; 155:1273-1276. Ramirez JA. Switch therapy in community-acquired pneumonia. Diagn Microbiol Infect Dis 1995; 22:219-223. Rein M, Gwaltney J, OBrien et al. Accuracy of Grams stain assessment in pneumococci in sputum. JAMA. 1978; 239(25): 26712673. Rello J, Rodriguez R, Jubert P, Alvarez V, and the Study Group for Severe CAP. Severe community acquired pneumonia in the elderly: Epidemiology and prognosis. Clin Infect Dis 1996; 23: 723-728. Research Committee of the British Thoracic Society and the Public Health Laboratory Service. Community-acquired pneumonia in adults in British hospitals in 1982-82: a survey of etiology, mortality, prognostic factors and outcome. QJ Med 1987; 62:195220. Rhew DC, Hackner D, Henderson L, Ellrodt AC, Weingarten SR. Clinical benefit of in-hospital observation in low-risk pneumonia patients after conversion from parenteral to oral therapy. Chest 1998; 113(1):142-146. Riley ID, Andrews M, Howard R, et al. Immunization with a polyvalent pneumococcal vaccine in adults. Lancet 1997; 1(8026); 13381341. Saniel M, Mendoza M, Taguinod C. Randomized controlled trial and economic evaluation of selected antimicrobial regimen in the outpatient treatment of CAP in adults 1998 (For publication). Shapiro ED, Berg ET, Austrian R, et al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991; 325:1453-1460. Simberkoff MS, Cross A, Al-Ibrahim M, et al. Efficacy of pneumococcal vaccine in high-risk patients. Results of a Veterans Administration Cooperative Study. N Engl J Med 1986;315(21):1318-1327. Sims RV, Steinma WC, McConville KH, King LR, Zwick WC, Schwartz JS. The clinical effectiveness of pneumococcal vaccine in the elderly. Ann Intern Med 1988; 108:653-657. Smit P, Oberhoizer D, Hayden-Smith S, Koornholf H, Hilleman M. Protective efficacy of pneumococcal polysaccharide vaccines. JAMA 1997; 238 (24):2613-2616. Sombrero LT, Espara GA, Soriano MVC, Capeding MRZ. Serotype distribution and antimicrobial susceptibility pattern of invasive Streptococcus pneumoniae and H. influenzae in Filipino children (1991-1994). In Program and Abstracts of the First National Pediatric Infectious Disease Conference, Monterey, California. 1995: 151. Stout JE, Yu VL. Legionellosis. N Engl J Med 1997; 337(10):682-686. Sunio GCG, Cesario RG. Sputum gram stain and culture in community-acquired and nosocomial pneumonia: a comparative study. Makati Medical Center Proceedings, 1994; 8:25-28. Thorsteinsson S, Musher D, Fagan T. The diagnostic value of sputum culture in acute pneumonia. JAMA 1975; 233(8):894-895. Torres A, Serra-Batlles J, Ferrer A, et al. Severe community-acquired pneumonia. Epidemiology and prognostic factors. Am Rev Respir Dis 1991; 144:312-318. Tremolieres F, de Kock F, Pluck N, Daniel R. Trovafloxacin versus high-dose amoxicillin (1 g three times daily) in the treatment of community-acquired bacterial pneumonia. Eur J Clin Microbiol Infect Dis 1998; 17:447-453.

Tupasi TE, Chua NC, de Leon LE. Streptococcus pneumoniae in community-acquired pneumonia. Phil J Intern Med 1981; 19(1): 189196. Winberg, GA, Spitzer ED, Murray PR, et al, and the BOSTID Haemophilus Susceptibility Study Group. Antimicrobial ssusceptibility patterns of Hemophilus isolates from children in eleven developing nations. Bull WHO, 1990; 68(2):179-184. Woodhead M. Prospective study of the etiology and outcome of pneumonia in the community. Lancet 1987:671-674. Zachairah J. A randomized, comparative study to evaluate the efficacy and tolerability of a 3-day course of azithromycin versus a 10 day course of co-amoxyclav as treatment of adult patients with lower respiratory tract infections. J Antimicrob Chemother, 1996, 37 Suppl C; 103-113.

APPENDICES Appendix I Grading System for Recommendations: Categories reflecting the strength of recommendation GRADE A B C D E Appendix II Quality Filters in assessing the evidence from the literature 1. Studies on effectiveness of treatment and accuracy of diagnostic test a. b. c. d. e. f. A randomized controlled trial (RCT) that demonstrates a statistically significant difference in at least one major outcome variable: survival or death OR if the difference is not statistically significant, an RCT of adequate sample size to exclude 25% difference in relative risk with 80% power, given the observed results. An RCT that does not meet the level 1 criteria A non-randomized trial with concurrent controls selected by some systematic method (not selected on the basis of perceived suitability for one treatment of the treatment options) Before-after study or case series of at least 10 patients with historical controls or controls drawn from other studies. Case series of at least 10 patients without controls Case series fewer that 10 patients or case reports. DEFINITION Good evidence to support a recommendation for use Moderate evidence to support a recommendation for use Poor evidence to support a recommendation against use Moderate evidence to support a recommendation against use Good evidence to support a recommendation against use

Level of quality of evidence for treatment trials Level I II III Criteria Evidence from at least one properly randomized controlled trial (Criteria a and be are satisfied) Evidence from at least one well designed clinical trial without randomization, from cohort or case-control analytic studies (preferable from more than one center), from multiple-time series, or from dramatic results in uncontrolled experiments (criteria 3-6 above). Evidence from opinions of respected authorities on the basis of clinical experience, descriptive studies, or report of expert committees.

2. Studies on the Accuracy of Diagnostic Tests Criteria for evaluating quality of evidence of studies on the accuracy of diagnostic tests a. b. c. d. There was an independent interpretation of the result of the diagnostic test (without knowledge of the result of the gold standard). There was an independent interpretation of the result of the gold standard (without the knowledge of the result of the diagnostic test). The study patients consisted of > 50 consecutive patients suspected (but not known) to have the disorder of interest. The diagnostic test and the gold standard are both described in sufficient detail to allow reproducibility.

e.

The study population consists of at least 50 patients with and 50 patients without the disorder of interest.

Level of quality of evidence based on a study of the accuracy of a diagnostic test I II III IV V a+b+c+d a+b+d+e Retrospective study Patients were non-consecutive, selected because of definitive results of the finding under study Unclear gold standard or poorly defined population

3. Studies on prognosis or causation Criteria for assessing quality of evidence A B C D E An inception cohort was chosen Reproducible inclusion and exclusion criteria were used Follow-up was complete for at least 80% of subject Statistical adjustment was carried out for confounders extraneous factors Reproducible descriptions of outcome measures were used

Level of Quality of Evidence I II III IV V VI All of the following criteria must be satisfied An inception cohort was selected but only 3 of 4 remaining criteria were satisfied An inception cohort was selected but only 2 of 4 remaining criteria were satisfied An inception cohort was selected but only 1 of 4 remaining criteria were satisfied An inception cohort was selected but only 1 of 4 remaining criteria were satisfied None of the 5 criteria was met.

4. Review Articles Criteria for evaluating quality of evidence A B C D Comprehensive search for evidence Avoidance of bias in the selection of articles Assessment of the validity of each cited article Conclusions supported by the data and analysis presented

Criteria of quality of evidence based on above criteria I II III IV V All 4 of the following criteria must be met 3 of the 4 criteria are met 2 of the 4 criteria is met 1 of the 4 criteria is met None of the 4 criteria are met

Task Force on Community-Acquired Pneumonia Thelma E. Tupasi, MD PSMID Chair Joselito R. Chavez, MD PCCP Member Benilda B. Galvez, MD PCCP Member Ismael G. Sumagaysay, MD PSMID ID Fellow Myrna T. Mendoza, MD PSMID Co-Chair Jennifer A. Chua, MD PSMID Member Felicita S. Medalla, MD PSMID Member Cecille A. Taguinod, MD PSMID ID Fellow Vilma M. Co, MD PSMID Rapporteur Remedios F. Coronel, MD PSMID Member Ma. Imelda D. Quelapio, MD PSMID ID Fellow Ma. Lourdes A. Villa MD PSMID ID Fellow

This project was supported by an educational grant from the Pfizer Philippines Foundation, Inc. We acknowledge with thanks the contributions of the panel of experts and participants of the public forum representing different institutions and organizations listed hereafter.

Panel of Experts and Public Forum Participants Alipio Abad, MD (MMC) Jesus Abello, MD (DOH) Angeles Tan-Alora, MD (STUH) Bolen Arribe, MD (Searle) Tito Atienza, MD (PCCP) Abundio Balgos, MD (UP-PGH) Fernando Ayuyao, MD (PHC) Francisco Barros, MD (PCEMAC) Gerardo Beltran, MD (PCR) Bernadeth Bringas, MD (VMMC) Danilo Cacanindin, MD (PCCP) Ananias Cornejo, MD (PCEMAC) Teresita de Guia, MD (PHC) Donna de Padua, MD (PCEMAC) Dina Diaz, MD (LCP) Jose Escaner (Philamcare) Annie Francisco, MD (PAFP) Alberto Gabriel MD (AFPMC) Merci Gappi, MD (SLMC) Merlou Sibonia (Abbott) Institutions Armed Forces of the Philippines Medical Center (AFPMC) Cebu Institute of Medicine (CIM) Dagupan General Hospital (DGH) Davao Doctors Hospital (DDH) Department of Health (DOH) Iloilo Doctors Hospital (IDH) Lung Center of the Philippines (LCP) Makati Medical Center (MMC) Philippine Heart Center (PHC) Organizations Abbott Laboratories American College of Chest Physicians Philippine Chapter (ACCP-PC) G.D. Searle Medical Observer Merck Sharp and Dohme, Philippines (MSD) Pfizer, Philippines Philamcare Philippine Academy of Family Physicians (PAFP) Philippine College of Chest Physicians (PCCP) Philippine College of Emergency Medicine and Acute Care (PCEMAC) Philippine College of Physicians (PCP) Philippine College of Radiology (PCR) Philippine Society for Microbiology and Infectious Diseases (PSMID) United Laboratories Wyeth Philippines Research Institute for Tropical Medicine (RITM) San Lazaro Hospital (SLH) Santo Tomas University Hospital (STUH) St. Lukes Medical Center (SLMC) University of the East Ramon Magsaysay Memorial Medical Center (UERMMMC) University of the Philippines Phil. General Hospital (UP-PGH) Veterans Memorial Medical Center (VMMC) Antonio Gonzaga, MD (UP-CM) Graciela G. Gonzaga (STUH) Andres Gumban, Jr., MD (PCCP) Elfleda Hernandez MD (CIM) Eduardo Jamora, MD (ACCP-PC) Mario Juco, MD (PCCP) Rene Juaneza, MD (IDH) Isaias Lanzona, MD (STUH) Suzette Lazo, MD (Unilab) Joselito Legaspi, MD (PCR) Benjamin Limson, MD (MMC) Marilla Lucero, MD (RITM) Socorro Lupisan, MD (DOH) Felisa Matanguihan, MD (UP-PGH) Parkesh Mansukhani, MD (DDH) Marilyn Ong-Mateo (STUH) Cecilia Montalban, MD (UP-PGH) Manny Nacua (Wyeth) Eduardo Nievera, MD (PCR) Gregorio Ocampo, MD (MMC) Francis Perfecto (Abbott) Tomas Realiza, MD (SLMC) Camilo Roa, MD (UP-PGH) Rodrigo Romulo MD (MMC) Roberto Ruiz, MD (PAFP) Ellen Sanchez, (Medical Observer) Ramon Santos-Ocampo, MD (PCR) Johnny Sinon, MD (PCEMAC) Beaver Tamesis, MD (MSD) Daniel Tan, MD (UERMMMC) Paul Tan, MD (MMC) Eric Tayag MD (DOH) Bienvenido Tiangco, MD (Abbott) Jaime Tomas, MD (PCR) Jun Umali (Abbott) Romulo Uy, MD (Cotobato) Ivan Villespin, MD (STUH) Jennifer Mendoza-Wi (DGH) Ma. Bella Siasoco, MD (UP-PGH)