Over the past 10 years, several guidelines have been published in response to evolving knowledge about CAP and antibiotic-resistant pathogens. In 2000, guidelines of the Infectious Diseases Society of America (IDSA) and of the Canadian Infectious Diseases Society (CIDS), in association with the Canadian Thoracic Society (CTS), were published simultaneously. These guidelines reviewed the epidemiology, diagnosis, risk factors, management, and treatment of CAP in depth. A recently published update of CAP management addressed new concerns and treatment approaches developed since 2000. A significant aspect of the more recent guidelines has been support for the use of prognostic scoring to identify patients who should be admitted to hospital. Past surveys have suggested wide variation between hospitals in both Canada and the United States in terms of length of stay for patients with CAP. Differences in the length of stay may be attributed to physicians overestimating the risk of death among patients with CAP, which could result in unnecessary hospital admissions. As a result, criteria or prognostic factors have been developed to assist physicians in identifying patients who should be admitted.

The most common method is the Pneumonia Severity Index (PSI), which was developed by Fine and others to identify patients with CAP at low risk of death who can be managed as outpatients (Figure 1). Factors associated with mortality were derived from a database of over 14 000 patients and were validated in over 40 000 patients (Table 2). The PSI allows patients to be classified into 5 risk classes. In the first stage of a 2-step process, patients are screened according to age, comorbidities, and physical findings to identify low-risk patients (class I), who may safely be managed as outpatients. Patients in classes II to V are assigned weighted scores according to age, comorbidities, and physical, radiologic, and laboratory findings. Class I patients have the lowest risk of mortality (0.1%). Patients in classes II and III may also be managed as outpatients since the risk of mortality is less than 1%, although some class III patients may require a brief hospital stay. In contrast, patients in classes IV and V must generally be admitted to hospital because of their high mortality risk (9% to 27%). Use of the PSI in association with treatment guidelines may result in cost savings for institutions treating patients with CAP. erectalis

Figure 1. Prediction rules for assessment

Figure 1. Prediction rules for assessment of mortality risk and recommendations for site of care. Reproduced, with permission, from Gin AS, TAilor SAN. Community-acquired pneumonia. Can J Hosp Pharm 2001;54 Suppl 1:1–16. © Canadian Society of Hospital Pharmacists.

Canadian recommendations (from the CIDS and CTS) are presented in Table 3. These recommendations were derived through expert consensus and are not necessarily based on randomized clinical trials. Recommendations for use of antibiotics in the treatment of CAP take into consideration the site of care, probable pathogens, prevalence of antibiotic resistance, and the empiric nature of initial CAP management. £-Lactam antibiotics, macrolides, respiratory fluoroquinolones, and doxycycline have all been used for empiric treatment of CAP. The advantages, disadvantages, and adverse effects of these agents have been presented in recent reviews. For outpatient treatment, macrolides (erythromycin, azithromycin, and clarithromycin) are generally recommended. For patients with comorbidities and/or exposure to steroids or antibiotics, respiratory fluoroquinolones (agents with activity against S. pneumoniae), such as levofloxacin, gatifloxacin, and moxifloxacin, are recommended. For nursing home residents, a respiratory fluoroquinolone or amoxicillin-clavulanate plus a macrolide may be used. For patients requiring admission to hospital, a respiratory fluoroquinolone is recommended
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Table 2. Risk Factors for Death in Patients with Community-Acquired Pneumonia
Age > 50 years
Male sex
Residence in a nursing home
Concurrent illness (neoplastic disease, congestive heart failure,
cerebrovascular disease, renal disease, liver disease)
Altered mental status
Pulse  125/min
Respiratory rate  30/min
Systolic blood pressure < 90 mm Hg
Temperature < 35°C or  40°C
Blood urea nitrogen  11 mmol/L
Glucose 14 mmol/L
Hematocrit < 30%
Sodium < 130 mmol/L
Partial pressure of oxygen < 60 mm Hg
Arterial pH < 7.35
Pleural effusion

as the initial agent for the empiric treatment of CAP. For patients admitted to the ICU, other pathogens such as P. aeruginosa or other gram-negative enteric pathogens may need to be considered and therapy adjusted accordingly. For pseudomonal pneumonia, recent guidelines have suggested combining an antipseudomonal 6-lactam with a fluoroquinolone or an aminoglycoside. In vitro synergy has been demonstrated with the 6-lactam-aminoglycoside combination but not with the 6-lactam- fluoroquinolone combination; the latter exhibited an additive but not antagonistic effect.

The duration of treatment for CAP ranges from 7 to 21 days depending on the severity of illness. As previously indicated, the increasing use of fluoroquinolones has led to concerns that rising fluoroquinolone resistance may negate the usefulness of these agents for CAP within 5 to 10 years. Once the pathogen and antibiotic susceptibilities are known, consideration should be given to streamlining therapy according to results, i.e., use of focused, less broadly active agents. IV administration of penicillin, for example, may be used for nonmeningeal PRSP infections such as CAP with MICs of up to 4 pg/mL.
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More recently, however, the IDSA has recommended that cefotaxime and ceftriaxone be the preferred IV agents for treatment of pneumococcal pneumonia (with­out meningitis) due to strains of S. pneumoniae with reduced penicillin susceptibility but with cefotaxime or ceftriaxone MICs less than 2 pg/mL. For cefotaxime and ceftriaxone, use of the new break-points assumes minimal dosing of 1 g q8h in adults or 50 mg/kg q8h in children. These recommendations are based on new interpretative standards for cefotaxime and ceftriaxone defining nonmeningeal and meningeal break-points. Strains of S. pneumoniae causing nonmeningeal infection are considered resistant if cefotaxime and ceftriaxone MICs are greater than 4 pg/mL. Changes in the interpretative break-points have been made in recognition of the clinical success observed in patients with PRSP pneumonia. As clinicians apply the new interpretative break-points, the use of third-generation cephalosporins may increase. This change highlights the need for adequate susceptibility testing and understanding of local PRSP epidemiology.

Table 3. Antibiotic Recommendations of the Canadian Infectious Diseases Society and the Canadian Thoracic Society for Patients with Community-Acquired Pneumonia




Site of Care




First-Choice Antibiotict




Alternative Antibiotict




Outpatient


No modifying factors


Macrolide


Doxycycline


COPD, no antibiotics or steroids


New macrolide


Doxycycline


COPD, recent antibiotics or steroids


“Respiratory” fluoroquinolone



Amoxicillin—clavulanate


+


macrolide OR



SGC


+


macrolide


Suspected macro-aspiration



Amoxicillin—clavulanate


+


macrolide



“Respiratory” fluoroquinolone


+


clindamycin or metronidazole




Nursing home


“Respiratory” fluoroquinolone OR



amoxicillin—clavulanate


+


new macrolide



SGC


+


new macrolide




Medical ward


“Respiratory” fluoroquinolone



Second-generation or higher cephalosporin


+


macrolide




Intensive care unit


IV
“respiratory” fluoroquinolone


+


cefotaxime, ceftriaxone, or B-lactam/B-lactamase inhibitor


IV
macrolide


+


cefotaxime, ceftriaxone, or B-lactam/B-lactamase inhibitor


If
Pseudomonas aeruginosa

is suspected, antipseudomonal fluoroquinolone (e.g., ciprofloxacin)


+


antipseudomonal B-lactam or aminoglycoside



Triple therapy: antipseudomonal B-lactam (e.g., ceftazidime,
piperacillin—tazobactam, imipenem, or meropenem)


+


aminoglycoside (e.g., gentamicin, tobramycin, or amikacin)


+


macrolide^

Since the publication of the Canadian guidelines, new agents (e.g., telithromycin) and shorter courses of therapy have been explored for the treatment of CAP. The advantages of short-course therapy include lower costs, better compliance, fewer adverse events, and fewer office visits. Short-course therapy with macrolides (e.g., azithromycin), £-lactam antibiotics, and telithromycin44-46 has been explored. Telithromycin, a once-daily oral ketolide antibiotic, is a semisynthetic derivative of the macrolides.47 Although its mechanism of action is similar to that of the macrolides, telithromycin has greater affinity for the ribosomal target site and maintains activity even in the presence of macrolide-resistant 5. pneumoniae mediated by mefA or ermB. In comparative studies, telithromycin appears effective in the treatment of CAP, although its use in more severely ill patients requires further study. Tellier and others found that, among ambulatory patients, telithromycin administered for 5 or 7 days was as effective as clarithromycin administered for 10 days. In Canada, telithromcyin has recently been approved for a 7-day course of treatment for CAP.
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With respect to the respiratory fluoroquinolones, a higher dose of levofloxacin (750 mg orally or parenterally) was recently approved for the 5-day treatment of CAP. Dunbar and others found that levofloxacin 750 mg for 5 days (IV or PO) was as effective as levofloxacin 500 mg for 10 days (IV or PO) for the treatment of patients in PSI classes I to IV. The higher dose takes advantage of the concentration-dependent pharmacodynamic effect of the fluoroquinolones, which shortens the course of treatment. A comprehensive review of the pharmacodynamic activity of antibiotics has been published previously. The pharmacodynamic effect of antibiotics is generally classified as time-dependent (e.g., 6-lactams) or concentration-dependent (e.g., aminoglycosides, fluoroquinolones). For time-dependent antibiotics, maximum bactericidal activity is obtained if the concentration of the antibiotic remains above the MIC of the pathogen for 40% to 60% (or more) of the antibiotic dosing interval. In contrast, for concentration- dependent antibiotics, the higher the concentration, the greater the extent and rate of bactericidal activity.