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Editorial Comment

Alternative Treatment Options for Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia

Pasquale, Timothy R. PharmD, MBA, FIDSA Written as an editorial commentary regarding Arshad et al. Ceftaroline Fosamil for Treatment of Methicillin-Resistant Staphylococcus aureus Hospital-Acquired Pneumonia and Health Care–Associated Pneumonia: A 5-Year Matched Case-Control Evaluation of Epidemiology and Outcomes on pages 83–87 of the Journal.

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Infectious Diseases in Clinical Practice: March 2016 - Volume 24 - Issue 2 - p 67-68
doi: 10.1097/IPC.0000000000000377
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Nosocomial pneumonia (NP) is the second most common nosocomial infection encountered in the United States and is associated with significant morbidity, mortality, and use of health care resources.1 Nosocomial pneumonia includes hospital-acquired pneumonia (HAP), health care-associated pneumonia (HCAP), and ventilator-associated pneumonia (VAP). Methicillin-resistant Staphylococcus aureus (MRSA) is a common nosocomial pathogen and is reported to account for more than 60% of the clinical S. aureus isolates recovered in intensive care units within the United States.1 For the treatment of MRSA NP in the United States, there are 3 antibiotics approved for this indication, including vancomycin, linezolid, and telavancin.

Two of the most extensively evaluated treatment options for MRSA NP are vancomycin and linezolid. Vancomycin has long been considered the mainstay for treatment of serious MRSA infections as a result of published data and years of experience. Despite the years of use, there is an ongoing debate as to the preferred treatment option for MRSA pneumonia. The American Thoracic Society and Infectious Disease Society of America guidelines on the management of HCAP, HAP, and VAP recommend both vancomycin and linezolid as first-line agents.1 However, reports for the past 10 years have indicated high failure rates and poor clinical outcomes associated with vancomycin therapy even in the setting of appropriate initial therapy.2–5 A recent study demonstrated linezolid to have a higher clinical cure rate than vancomycin, although all-cause 60-day mortality rates and adverse events were similar.6 Linezolid may present certain clinical limitations, including if prolonged course is required (ie, myelosuppression) and if patients are taking serotonergic antidepressants (ie, serotonin syndrome).7

The third agent with approval for MRSA NP is telavancin, and it was found to be noninferior in 2 randomized, clinical trials compared with vancomycin in patients with MRSA HAP.8 However, telavancin also presents clinical challenges in patients with preexisting kidney insufficiency (ie, creatinine clearance ≤ 50 mL/minute), because a trend of increased mortality was noted in patients receiving telavancin compared with vancomycin.8 Furthermore, the prescribing information includes a note that telavancin should be reserved for use when alternative treatments are not suitable.8

Considering that current treatment options have limitations, alternative options are critically needed for the treatment of MRSA pneumonia. The study by Arshad et al9 in this issue reported the results of a comparative retrospective matched case-control study evaluating the effectiveness of ceftaroline fosamil (CPT-F) versus alternative antibiotic therapies, including vancomycin and linezolid, in hospitalized patients with MRSA HCAP or HAP. A total of 40 patients treated with CPT-F and 109 patients treated with alternative therapies were included in the study. Twenty of the 40 CPT-F patients were switched to CPT-F after failing on either vancomycin or linezolid. The average duration of therapy before the switch to CPT-F was 7 days. All 20 patients switched to CPT-F achieved clinical success. The authors found CPT-F to be as effective in regard to clinical success as vancomycin or linezolid for the treatment of MRSA HCAP or HAP.

Ceftaroline fosamil is a novel cephalosporin approved in 2010 with potent activity against MRSA isolates.10 Ceftaroline fosamil has Food and Drug Administration-approved indications for the treatment of community-acquired bacterial pneumonia (CABP) as well as acute bacterial skin and skin structure infections.10 The clinical utility of CPT-F in patients with MRSA pneumonia is unknown because of the lack of large randomized control trials involving MRSA pneumonia patients. In the 2 large, prospective, randomized clinical trials in patients with CABP, only 2 patients had MRSA isolated.11 The recent completion of a multicenter, randomized, double-blind study evaluating the efficacy and safety of CPT-F versus ceftriaxone plus vancomycin in adult subjects with CABP at risk of infection due to MRSA may address some concerns.12 However, this study was only in the setting of CABP and will not answer any questions in the MRSA NP population.

Despite the lack of large randomized control trials, recent literature supports an interest in the use of CPT-F as an alternative option for patients with MRSA NP. Casapao et al13 reported the experience from a retrospective, observational study of CPT-F use for various infections including pneumonia. A total of 527 patients received CPT-F for at least 72 hours during hospitalization, of which 80% received another antimicrobial before the start of CPT-F. Ninety-nine patients received CPT-F treatment for pneumonia, of which 68 patients received treatment for either NP or MRSA pneumonia. In patients receiving CPT-F for pneumonia, 86% experienced clinical success, defined as resolution of all signs and symptoms of infection with no further need for escalation of antibiotic therapy.

A single-center experience with CPT-F in 10 patients with MRSA NP was described in a retrospective case series.14 Six of the patients had HCAP, 3 patients with HAP, and 1 patient with VAP. Similar to Arshad et al,9 9 of the 10 patients received previous anti-MRSA therapy before the initiation of CPT-F.14 One factor in consideration for the switch in therapy was high vancomycin minimum inhibitory concentration (≥1.5 μg/mL) of the MRSA isolate encountered. Three of the patients pursued palliative care before completion of antibiotic therapy and died off antibiotics. Six of the remaining 7 patients were considered to have clinical cure. One patient had a microbiologic and clinical relapse 1 week after the end of CPT-F therapy.

Kaye et al15 reported the results of CPT-F use in patients with HAP/VAP from a registry, the Clinical Assessment Program and Teflaro Utilization Registry. The Clinical Assessment Program and Teflaro Utilization Registry is a retrospective cohort study designed to collect information on the contemporary clinical use of CPT-F.15 A total of 40 patients with NP, including 27 with HAP and 13 patients with VAP were included. The most common pathogen encountered was MRSA, 44% of HAP and 54% of VAP patients. The overall clinical success rate of CPT-F in HAP/VAP patients was 75%. In evaluating the MRSA HAP/VAP patients, CPT-F had a clinical success rate of 58%. The majority of patients with MRSA pneumonia received CPT-F as second-line therapy after failure of previous antibiotics, most commonly vancomycin (74% of patients with HAP and 62% of patients with VAP).

In considering the existing literature, vancomycin and linezolid remain as first-line treatment options for MRSA NP. The best approach for those patients who fail to respond to first-line agents or are not suitable for first-line agents remains to be defined. Telavancin has large randomized control trials demonstrating noninferiority compared to vancomycin, but poses clinical concerns from an efficacy standpoint in patients with renal insufficiency. On the other hand, the study by Arshad et al9 in this issue and other reports in recent literature demonstrate CPT-F to be an effective alternative option. Majority of the patients described in the recent reports received CPT-F as salvage therapy, yet experienced favorable outcomes. Large prospective, randomized control trials are warranted to establish the role of CPT-F in the setting of MRSA NP.


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