Current Clinical Practice in the Management of Community-Acquired Pneumonia: An Appraisal

Ma. Lourdes A. Villa, M.D.,1 Ismael Sumagaysay, M.D., Maribel We, M.D.,3 Vilma Co, M.D.,4 Myrna T. Mendoza, M.D.,5 Thelma E. Tupasi, M.D.6 and Remedios F. Coronel, M.D.7
(1Fellow, Infectious Disease Section, Department of Medicine, Makati Medical Center, 2Fellow, Infectious and Tropical Diseases Section, Department of Medicine, Santo Tomas University Hospital, 3Fellow, Infectious Diseases Section, Department of Medicine, UP-PGH, 4Consultant, Infectious Disease Section, Department of Medicine, Makati Medical Center, 5Chief, Infectious Diseases Section, Department of Medicine, UP-PGH, 6Chief, Infectious Disease Section, Department of Medicine, Makati Medical Center and 7Chief, Infectious and Tropical Diseases Section, Department of Medicine, Santo Tomas University Hospital) ABSTRACT A retrospective and descriptive study to determine current practices of physicians in the management of patients with community acquired pneumonia (CAP) was done in 3 Metro Manila Hospitals. Clinical charts of 198 hospitalized adult patients with CAP were reviewed. Data on age, sex, severity of illness, comorbidity, bacteriologic findings, chest X-ray, antibiotic therapy, length of hospital stay (LOS), and outcome were analyzed. Forty one (20.7%) of these patients did not require hospitalization (20 minimal and 21 low-risk CAP). Of the remaining patients, 120 were moderate and 37 had high-risk CAP. Only 6(16%) of the latter were appropriately admitted at ICU. Recommended antibiotics were used in 4 (20%), 10 (48%), 36 (30%), and 5 (14%) for minimal, low-risk, moderate, and highrisk CAP, respectively. Case fatality rate was 5.5% for moderate and 20% for high-risk CAP treated with recommended drugs, compared to 3.5% and 37.5% respectively, for those given other agents. The management of 72.2% of patients studied was not in conformity to the recommended guideline. Unnecessary hospitalization was noted in 20.7% of patients. Although no significant difference in case fatality rate and LOS was noted in the patients given recommended versus other drugs, following the guidelines could possibly reduce the cost of treatment. (Phil J Microbiol Infect Dis 1999; 28(4):121-127) Key words: community-acquired pneumonia, clinical practice guideline
2

INTRODUCTION Community acquired pneumonia (CAP) remains a major cause of death worldwide accounting for an estimated 5 million deaths per year. In developed countries, the antimicrobial era has brought a 66% reduction in the crude mortality rate associated with the disease. It remains the most frequent infectious cause of death and the 6th leading cause overall in the United States, resulting in more than 500,000 hospital admissions annually in adults, with a mortality rate at 20 to 40%.1,2 In the Philippines, there are more than 40,000 cases of CAP annually. More than 50% are admitted in the hospital. Pneumonia is considered the 3rd leading cause of death and the 4th leading cause of morbidity.3 Clinical practice guidelines on CAP have recently been developed by a multi-disciplinary task force utilizing evidence based approach and consensus building in collaboration with the consortium of societies and organizations comprising the Philippine Guidelines Group in Infectious Diseases (PPGGID).4 This study was undertaken to determine baseline data on the current clinical practices in the management of CAP among Filipino physicians. Management decisions on hospitalization, utilization of bacteriologic studies, and empiric initial therapy in 3 major tertiary hospitals in Metro Manila were

analyzed utilizing the guidelines as basis. The clinical outcome of patients was correlated with management decisions. MATERIALS AND METHODS This is a retrospective analysis of patients admitted for CAP at the Philippine General Hospital (PGH), Santo Tomas University Hospital (STUH) and the Makati Medical Center (MMC) from July to September 1997. Using a standard clinical research form, socio-demographic data such as age, sex, severity of illness, co-morbidity, bacteriologic findings, chest X-rays, days of hospitalization and clinical outcome were noted. The decision to hospitalize a patient was evaluated based on the presence or absence of risk factors for a complicated course. The quality of sputum specimens, if obtained, was assessed based on the number of polymorphonuclear cells per power field (PMN/LPF) and the number of epithelial cells (EC/LPF) by gram stain. Results of blood sputum culture and sensitivity test (CS), if done, were analyzed. The initial empiric antibiotic therapy was classified as consistent with recommended drugs or not. Outcome variables included case fatality rate, mean days of hospital stay, and modification of antibiotics either for purposes of streamlining or because of treatment failure. Determination of frequencies was done using the software SPSS version 7.5.5 Chi-square test and Fischer exact test were used to detect significant difference of proportion between specified groups. The T-test was used to assess significant difference of mean days of hospital stay. The association was considered statistically significant if p <0.05. RESULTS Risk Stratification of CAP A total of 198 patients were included in the review. There were 109 (55%) females and 89 (45%) males. Majority of patients, 113 (57%) were 65 years of age. Ages ranged from 18 to 103 years with a mean age of 62 years. The risk stratification of the 198 patients is shown in Figure 1. Vital signs and radiographic findings predictive of a complicated course were noted in 157 patients. Of these 157 patients, 37(18.7%) had findings suggestive of high-risk CAP, while 120(60.6%) were considered as moderate-risk CAP. Of the remaining 41 patients, 21(10.6%) had co-morbid conditions and were classified as low-risk, while 20 (10.1%) were considered as minimal-risk category. Of the co-morbid conditions, cardiovascular disease (52%) was most commonly seen, followed by COPD/bronchiectasis (33%), diabetes mellitus (14%), neoplastic disease (14%), and chronic liver disease (14%). Findings of chronic renal failure and chronic alcohol abuse were seen in 1 (5%) patient each. Eight of these 21 patients had more than 1 co-morbid condition. Analysis, thereafter, has been confined only to moderate and high-risk CAP. Table 1 shows the findings predictive of a complicated course of CAP in 157 patients including 113 aged 65 years and above and 44 younger than 65 years. Of the older patients, 84 (74%) had chest radiographic finding or physical findings predictive for a complicated course of CAP and the remaining 29 (26%) were so classified based solely on age. Multi-lobar radiographic involvement was seen in 69 (44%) patients. This was more commonly noted among patients <65 years (59%) compared to the older patients (38%). Pleural effusion was noted in 13 (8%) and was more commonly seen in those < 65 years (14%) compared to older patients (6%). Abscess was seen in only 1 (2%) patient who was <65 years. Temperature > 40oC or < 35oC was noted in 53 (34%) patients including 43% of patients younger than 65 years and 30% of the older patients. Tachycardia > 125/min and tachypnea > 30/min were each seen in 18% and both were seen more frequently in the younger patients < 65 years of age (25% and 32%, respectively) compared to the older patients (15% and 13%, respectively). Aspiration was suspected in 5 (3%) and extra-pulmonary evidence of sepsis was noted in 6 (4%) patients. Among patients younger than

65 years, these were noted in 1 (2%) and 4(9%) patients respectively while in older patients this was noted in 4 (3%) and 2(2%), respectively.
Figure 1. Algorithm: Management-oriented risk stratification of community-acquired pneumonia in immunocompetent adults. Modified from TFCAP guideline. CAP Any of the following: 1. age 65 2. RR 30/min 3. PR 125/min 4. T 40 or 35oC 5. CXR: multilobar, pleural effusion, abscess, progression of lesion to 50% within 24 hours 6. suspected aspiration 7. extrapulmonary evidence of sepsis NO Any of the ff: 1. Diabetes mellitus 2. Neoplastic diseases 3. Neurologic disease 4. Congestive heart failure 5. Renal insufficiency 6. COPD 8. Chronic alcohol abuse NO MINIMAL RISK (CAP I) OUTPATIENT Table 1. Findings predictive of a complicated course in patients with community-acquired pneumonia Clinical Findings Age >65 years N=113 n (%) 43 7 0 34 17 15 4 2 29 (38) (6) (30) (15) (13) (3) (2) (26) Age <65 years N=44 n (%) 26 6 1 19 11 14 1 4 0 (59) (14) (2) (43) (25) (32) (2) (9) Total N=157 n (%) 69 13 1 53 28 29 5 6 29 (44) (8) (1) (34) (18) (18) (3) (4) (18) NO Any of the following: 1. Shock or signs of hypoperfusion: (altered mental state, urine output < 30 ml/hr 2. PaO2 < 60 mmHg or acute hypercapnea (PaCO2 > 50 mmHg) at room temperature

YES

YES HIGH RISK CAP (IV)

ICU ADMISSION

YES UNSTABLE NO LOW RISK (CAP II) OUTPATIENT

YES

MODERATE RISK CAP (III) WARD ADMISSION

Chest X-ray Multi-lobar involvement Pleural effusion Abscess Temperature >40 C or <35 C PR >125/min RR >30/min Suspected aspiration Extrapulmonary evidence of sepsis Patients with none of the above

Among the 157 patients with features predictive of a complicated course, 37 patients had features of high-risk CAP as shown in Table 2. Of the 37, only 6 were admitted to the ICU. Among patients with high-risk CAP, severe hypoxemia or acute hypercapnea was seen in 57%, followed by shock or signs of hypoperfusion such as hypotension, altered mental state, urine output at 30 cc/hr seen in 49%, 46%, and 16% of patients, respectively. Findings of shock or signs of hypoperfusion such as hypotension and altered mental state were comparable among high-risk CAP patients admitted at the ward (48%) and ICU

(50%). All patients admitted at the ICU had severe hypoxemia or acute hypercapnea at room air, which had to be corrected accordingly. This finding was seen in 48% of patients admitted at the ward. The case fatality rate for patients with high-risk CAP was 35.4% and was 16.7% in the ICU compared to 38.7% of those admitted in the regular ward.
Table 2. Features of high-risk community acquired pneumonia Findings Shock or signs of hypoperfusion Hypotension Altered mental state U.O.< 30 cc/hr PaO2 < 60 mmHg or acute hypercapnea (PaCO2 > 50 mmHg) at room air Case Fatality Rate Ward Admission N=31 n % 15 14 4 15 12 (48) (45) (13) (48) (38.7) ICU admission N=6 n % in 3 (50) 3 (50) 2 (33) 6 1 (100) (16.7) Total N=37 n % 18 17 6
21

(49) (46) (16)

(57)

13

(35.4)

Bacteriologic Studies Bacteriologic studies included sputum GS in 74 patients including 10 (50%) minimal, 10 (48%) low-risk, 41(34%) moderate and 13(35%) high-risk patients. Figure 2 shows the analysis of sputum gram stain done in 74 patients. Only 32 (43%) of these specimens fulfilled the criteria for an adequate or appropriate specimen. A predominant organism was reported in only 9 of 32 specimens. Of the 32 patients with appropriate sputum specimens, blood cultures were done in 13 and blood cultures were likewise done in another 35 patients. These 48 patients included 29 with moderate and 19 high-risk patients (Table 3). Of the 48 blood cultures done, 26 (54%) yielded positive results; 14 (48%) of 29 patients with moderate risk and 12(63%) of 19 patients with high-risk CAP. S pneumoniae was isolated in 9 patients, followed by Klebsiella spp (7), Escherichia coli (7), Staphylococcus aureus (2) and Pseudomonas sp.(1). There was correlation of the gram stain [predominant organism: gram (+) cocci in pairs] and blood cultures in 5 patients who all had Streptococcus pneumoniae bacteremia; 3 of these had moderate to heavy growth of Streptococcus pneumoniae in sputum culture. Of the remaining 4 patients with a predominant organism reported from sputum gram stain, 2 had gram (+) cocci reported singly or in pairs and blood cultures grew Staphylococcus aureus, 1 had gram (+) cocci in clusters but grew Klebsiella sp. in blood culture. The last patient had no blood culture done. The treatment of the 26 patients with (+) blood cultures was based on the isolated pathogen in 18, with 1 patient expiring after 1 day following modification of antibiotics. Five died and 1 patient was discharged before blood culture results were available. Two were continued on their initial antibiotic therapy; ciprofloxacin in 1 patient with S. pneumoniae and cefuroxime in another patient with S. aureus bacteremia. Both patients improved. Evaluation of Management Decisions Table 4 shows the evaluation of decisions on hospitalization based on risk categories of patients with CAP. Forty-one (20%) of the 198 patients admitted were of minimal (20) or low-risk (21) category who would have been suitable for outpatient care. Hospital admission for these 41 patients was therefore deemed inappropriate. Since this study only reviewed hospitalized patients, those with minimal or lowrisk CAP seen at that time and not admitted were not included. Of the remaining 157 patients, 37 patients were considered to have high risk CAP who should have required ICU admission; only 6 (16%) were admitted in the ICU while 31 (84%) were admitted in a regular ward or room. The choice of regular rooms was therefore deemed inappropriate in these 31 patients. Blood culture is the gold standard in the etiologic diagnosis of CAP. It is specifically recommended in those with moderate to high risk CAP requiring hospitalization. Of 157, only 48 (30%)

of these patients had a blood culture taken. It was deemed inappropriate that blood cultures were not obtained in the remaining 109 (70%) patients; 91 moderate and 18 high-risk CAP patients.

Figure 2. Analysis of sputum gram stain done in 74 patients

Sputum smears (N=74) PMN>25/lpf EC<10/lpf (N=32) Predominant organism reported (N=9) G (+) cocci,pairs (N=7) . Blood cultures S.aureus (N=2) G (+) cocci clusters (N=2) Blood cultures Klebsiella sp (N=1) No blood culture (N=1) PMN>25/lpf EC >10/lpf (N=25) Inappropriate PMN <25/lpf (N=17)

S.pneumoniae (N=5)

Table 3. Pathogens isolated from blood cultures obtained from patients with moderate risk and high risk CAP
Pathogen S.pneumoniae S.aureus
Klebsiella spp E.coli

Moderate-Risk CAP N=19

6 1 3
3 1 14 (48)

High-Risk CAP N=29 3 1

4

. Total N=48 9 2
7
7

4
0

Pseudomonas spp. All

1
26 (54)

12 (63)

Table 4. Evaluation of management decisions made on 198 patients with CAP According to CAP Guidelines 41 37 157 Appropriate
No. (%) (16)

Inappropriate
No. 41 31 (%) (100) (84)

Outpatient Care For minimal and low-risk CAP ICU admission for high-risk CAP Blood cultures recommended for moderate and high-risk CAP

48

(30)

109

(70)

Treatment and Clinical Outcome The recommended empiric agents were used in a minority of cases reviewed. For minimal-risk CAP, these included macrolide in 3 and amoxicillin in 1 patient. Other agents used were cephalosporins (9), quinolones (2), and beta lactam/beta-lacatamase inhibitor IV (5). For low-risk CAP, the recommended agents included second generation cephalosporin alone in 6 patients or in combination with macrolides in another 4 patients. Cotrimoxazole, beta lactam/beta-lactamase inhibitor (PO) alone or in combination with macrolide was each given in 1 patient each. Other agents used were parenteral coamoxiclav in 8 patients. There was no modification of the initial choice of antimicrobials due to treatment failure among patients with minimal and low-risk CAP. There was no mortality among these patients. Mean hospital stay for minimal-risk CAP was 4.2 + 1.9 days for those given recommended antibiotics vs. 5.4 + 2.3 days for those given other agents; for low-risk CAP it was 5.7 + 3.1 vs 7.5 + 6.7, respectively.

Table 5 shows the use of recommended and other drugs and the clinical outcome of patients with moderate and high-risk CAP. Among the recommended agents for moderate-risk CAP, cephalosporins (IV) with macrolide were used in 34 patients or co-amoxiclav (IV) with macrolide in 2. Other agents given for these patients were monotherapy of cephalosporins (25), co-amoxiclav (26), or macrolide (10) or quinolones (10), anti-pseudomonal agents (3), cotromoxazole (2), or combination therapy in 8 patients. Among patients with high risk CAP, the use of recommended agents such as anti-pseudomonal agents with erythromycin IV was seen in 5 patients. Other agents used included monotherapy with antipseudomonal agents (8), other cephalosporins (5), beta-lactam/beta-lactamase inhibitor (6). Combination therapy with any of the above other agents was seen in 13 patients. Streamlining of initial parenteral antimicrobial therapy to an oral agent in patients who show adequate clinical response was noted in 18 of 58 patients given the recommended drugs and 58 of 140 patients who were given other agents. Modification of initial antibiotic therapy due to treatment failure was seen in 8 of moderate (4 of whom were given recommended agents) and 9 of high-risk CAP patients (2 of whom were given recommended agents). After the modification of therapy, these patients improved. The mean days of hospitalization for moderate-risk CAP was 7.2 + 3.3 vs 7.0 + 4.1 for those given recommended drugs vs. other drugs, respectively; and for high-risk CAP, it was 11.0 + 10.1 vs 12.4 + 7 .4 days, respectively. Case fatality rate for mode-rate risk CAP patients who received recommended antibiotic therapy was 5.6% against 3.5% who received other antibiotics. Among high-risk CAP patients, case fatality rate was 20% for those who used the recommended antibiotic therapy against 37.5% who received other antibiotics. Overall, case fatality rates for moderate and high-risk CAP patients who received recommended antibiotic therapy was lower at 7.3% compared to 12.9% who received other antibiotics. Because of the small number of cases studied, differences in the mean hospital days and case fatality rate among patients given recommended and other agents showed no statistical significance.
Table 5. Empiric antibiotic therapy and outcome of patients with CAP Stratification Moderate Risk High Risk Empiric Antibiotic Therapy No. Recommended Other agents Recommended Other agents
36 84 5 32

Treatment modified for streamlining 18 36

0

Treatment modified due to failure

4 4 2 7 (11) (5) (40) (22)

Case fatality rate % 2 3

1

Mean hospital stay 7.2+1-3.3 7.0+/-4.1 11.0+/-10.1 12.4+/-7.4

(50) (43) (31)

(5.5) (3.6)
(20)

10

12

(37.5)

DISCUSSION Management guidelines for patients with CAP have been devised to provide bases for hospitalization, and for diagnostic and therapeutic approaches.4,6,7 In the initial assessment of a patient with CAP, the decision to hospitalize patients is based on a number of prognostic indicators that are significantly associated with a complicated course or with a fatal outcome. Several studies have shown a direct association between age > 65 years and mortality,8 and a complicated course.9 Chest X-ray findings of multi-lobar involvement was associated with mortality with Odds ratio of 3.1 (95% CI=1.9-5.1) and pleural effusion was associated with a complicated course with odds ratio of 2.8 (95% CI=1.4-5.8)10 Temperature of > 40oC or < 35, pulse rate > 125 beats/min,11 and respiratory rate > 30/min12 were also considered predictive factors for a complicated course. Non-adherence to the guidelines on admission may impose danger to patients. High-risk CAP requiring ICU treatment is frequent and represents some 18-36 % of CAP patients requiring hospitalization.13 In our study, thirty-seven (23.6%) of the 157 patients who should be hospitalized were high-risk CAP. Only 6 of these patients were actually admitted at the ICU. The case fatality rate was 16.7% among these patients compared to 38.7% among those not admitted to ICU.

A judicious use of bacteriologic studies is important in the management of CAP. Of the 74 sputum specimens studied, only 32 (43%) were appropriate and of these, only 9 reported a predominant organism. A correlation of the sputum GS was seen in only 5 of S. pneumoniae bacteremia and possibly in 2 patients with S. aureus bacteremia. This indicates that in the majority of sputum specimens studied, the specimen was inappropriate and no useful information was derived from them. On the other hand, of the small number of patients with moderate to high-risk CAP with blood cultures, a positive yield was obtained in more than half of cases and was utilized as bases for treatment in 18 of 26 patients with a positive yield. This illustrates the importance of blood cultures in the management of moderate to high-risk CAP. The physicians management of community-acquired pneumonia has been known to be varied. Although many studies and recommendations have been made, several factors influence ones decision regarding its management. Such factors include cost-effectiveness of the therapy, anecdotal experiences, drug factors (like the influence of pharmaceutical companies), host factors, social and moral issues. Published guidelines have reiterated the necessity of initial empiric treatment based on the likely pathogen involved. Use of recommended antibiotics was seen in only a minority of patients reviewed. Cost considerations favor streamlining of initial parenteral empiric broad-spectrum therapy to a narrowspectrum parenteral agent or an oral agent among patients who show adequate clinical response after 2-3 days.14 With the use of recommended agents among minimal and low-risk CAP, streamlining was unnecessary; it was done in 8 low-risk patients initially given parenteral antibiotics. Streamlining was done in 54 (45%) and 10 (27%) of mode-rate and high-risk CAP patients, respectively. Modification of initial antibiotics due to treatment failure was noted in 6.6% of mode-rate and 24% of high-risk CAP. In a meta-analysis of prognosis and outcomes of patients with CAP10 overall mortality rates ranged from 5.1% for hospitalized and ambulatory patients to 36.5% for ICU patients. Mortality rate for severe CAP remains high. This may go as high as 47-76%.11 This is consistent with our findings of a case fatality rate among high-risk CAP patients of 37.6% among those given other agents and 38.7% among those not admitted at the ICU. High mortality rates may be due to late admission in the course of illness, concomitant life-threatening co-morbidities, severely deranged physiologic parameters, or inadequate assessment and inappropriate antibiotics. Because of the small numbers studied, no statistically significant differences were noted in the case fatality rate and the mean duration of hospital stay in those given recommended versus those given other drugs. However, there was a trend for a higher case fatality rate among high-risk patients and a longer hospital stay among those given other agents. In this retrospective study, we observed the nonconformity to set guidelines in the majority of cases as also previously noted.15 Although clinical response has been seen with the use of other drugs not recommended by the guidelines it is anticipated that compliance to the guidelines in the future may improve the final outcome of patients with CAP and possibly diminish the cost of management.
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