Antimicrobial Stewardship Targets in Community-Acquired Pneumonia

Antimicrobial stewardship programs (ASPs) are often tasked with addressing a wide scope of antimicrobial misuse with limited resources.

To focus their efforts, program administrators should target low-hanging fruit and commonly encountered conditions such as community-acquired pneumonia (CAP).^1,2 Nationally, CAP is responsible for about 600,000 hospital admissions per year.³ If each of those admitted patients were to receive 5 to 7 days of antimicrobial therapy, that would account for a minimum of 3 million to 4.2 million days of antimicrobial therapy. At Alaska Medical Center in Anchorage, optimizing antimicrobial therapy in patients with CAP has annually accounted for 19% to 21% of ASP interventions. Given the frequency of CAP-related admissions and the overall antimicrobial consumption in these patients, special attention should be paid to optimizing antimicrobial therapy in this population.

Effective antimicrobial stewardship begins with appropriate diagnosis. CAP can be difficult to diagnose, given that presenting symptoms may lead to a wide differential, including cancer, embolism pulmonary edema, and viral infection.⁴ This considered, several diagnostic tools, such as respiratory pathogen panels (RPPs), have gained attention since the publication of the Infectious Diseases Society of America (IDSA) CAP guidelines in 2007.⁵ These RPPs, which typically use polymerase chain reaction (PCR) technology, contain primers for multiple respiratory viruses and a few atypical bacteria. The 2016 IDSA guideline regarding the implementation of an ASP specifically recommends that rapid viral testing be used for respiratory pathogens in an attempt to curb inappropriate antimicrobial prescribing (weak recommendation/low-quality evidence).² Conversely, some institutions have found that RPPs function to increase diagnostic accuracy but have little impact on reducing antimicrobial durations.^6,7 Onboarding of an RPP should be accompanied by provider education to specify in which clinical circumstances the test may be most useful. Special attention should also be given to rapidly addressing results and pairing RPP use with other diagnostic markers, such as procalcitonin (PCT). PCT, an amino acid precursor of calcitonin, has been shown to elevate above-normal physiologic levels in bacterial lower respiratory tract infections (LRTIs) but not in viral infections. Levels rise within 2 to 4 hours of onset, peak between 8 and 24 hours, and have a half-life of about 24 hours.⁸ Use of PCT has been shown to decrease inappropriate antibiotic initiation and the duration of therapy in patients with LRTIs.⁹ As such, PCT is likely a reasonable target for ASPs looking to optimize both antibiotic therapy and diagnostic accuracy in CAP.

Regarding selection of appropriate drug regimens, the 2007 IDSA CAP guideline suggests either monotherapy with a respiratory fluoroquinolone or a third-generation cephalosporin in combination with a macrolide.⁵ The aim of both regimens is to provide coverage of both atypical and typical CAP pathogens.^3,4 Despite the findings of one recent Dutch study in non—intensive care unit CAP, most of the primary literature suggests that empiric coverage of atypical pathogens continues to contribute to improved outcomes in hospitalized patients with CAP.^3,10 Thus, deviation from the inpatient regimen recommended by the IDSA does not appear prudent. However, when selecting a regimen from the 2 guideline compliant options, it appears that the β-lactam—macrolide combination confers superior clinical outcomes to those of a respiratory fluoroquinolone.^11-13 Given these data, coupled with the undesirable adverse event (AE) profile of fluoroquinolones and no need for antipseudomonal coverage in most patients with CAP, it may be prudent for ASPs to focus on using β-lactam—macrolide regimens as the first-line treatment for inpatients with CAP and reserving fluoroquinolones for those with true penicillin allergies.

Dose optimization is another target for ASPs in patients with CAP. Azithromycin is the most common macrolide used for atypical pathogen coverage, but the IDSA guideline does not recommend a specific dosing strategy.⁵ Comparable areas under the curve occur with administration of the same total dose of azithromycin (1.5 g) over 3 versus 5 days.¹⁴ Thus, 3 days of azithromycin therapy is appropriate for CAP, and programs may consider recommending 500 mg of azithromycin daily for 3 days. Ceftriaxone, the third-generation cephalosporin commonly used to treat CAP, has a dose range provided by the IDSA of 1 to 2 g daily.⁵ Early studies assessed both doses and found equal efficacy for treatment of moderate to severe CAP. Therefore, daily doses of 1 g may be sufficient for most patients.¹⁵ Two-gram doses may be more appropriate in obese patients because of increased volume of distribution or in those with CAP who are critically ill.

Despite the positive evidence behind intravenous (IV) to per oral (PO) conversion, this intervention is not always routinely performed.^16,17 Although the oral bioavailability of azithromycin is about 34% to 52%, the high, persistent concentrations of the drug in bronchial secretions support 1:1 IV to PO conversion.¹⁸ Given these pharmacokinetic properties, a low-hanging fruit for ASPs may be inclusion of azithromycin to automatic IV to PO interchange protocols.

A final ASP target in patients with CAP is optimization of antibiotic treatment duration. The IDSA recommends a minimum of 5 days, though 7 to 10 days is the usual treatment duration for patients with CAP reported in literature.⁵ According to several reports, antibiotic duration was decreased from a median of 10 days to 7 without negatively affecting clinical outcomes, and growing evidence suggests that even shorter durations can be safe and effective.^2,15,19 One of the major hurdles to shortening therapy is providing evidence to support early discontinuation. Use of patient-specific PCT trends during a course of therapy can support early discontinuation as PCT values normalize.⁹ As an acute phase reactant, PCT corresponds closely with the onset and resolution of bacterial infections.⁸ When levels are checked every 48 to 72 hours, a reduction to a value of <0.25 ng/mL, or a 80% to 90% reduction from peak values of >5 ng/mL, can serve as cutoff markers for safe antibiotic discontinuation.⁹ Although there are populations in which use of a PCT algorithm may be less useful, in the typical patient with an LRTI, it may lead to earlier discontinuation of antibiotics without increasing AEs.⁹

ASP programs, both new and well established, seeking to further refine management of CAP should focus efforts on these opportunities to optimize the diagnosis, drug selection, dosing, de-escalation, and duration of therapy within their institution.

Ryan W. Stevens, PharmD, BCPS, is an infectious diseases clinical specialist at Providence Alaska Medical Center in Anchorage. Ann-Chee Cheng, PharmD, is completing a PGY1 pharmacy practice residency at Providence Alaska Medical Center.

References

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