Successful Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia with Ceftaroline Fosamil

Abstract

Objectives

To describe a case of successful treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with ceftaroline fosamil after failure with vancomycin and daptomycin.

Case Summary

A 53-year-old female with a past medical history of cancer (unknown source/type) and hypothyroidism was admitted to the hospital with cervical and paravertebral abscess with suspected sepsis. In the emergency department (ED), magnetic resonance imaging (MRI) revealed possible spinal abscess and narrowing of the spinal canal. The patient was initiated on vancomycin 1,250 mg (~15 mg/kg) every 12 hours and cefepime 2 g every 8 hours empirically. On hospital day 4, blood and wound cultures revealed MRSA susceptible to vancomycin, but with a vancomycin minimum inhibitory concentration (MIC) of 2. Repeat blood cultures were also positive on hospital days 2 and 4. Per infectious disease team consult, therapy was converted to daptomycin 8 mg/kg/day. Although the patient responded well, acute kidney injury (AKI) on hospital day 15 prompted a change in therapy to ceftaroline fosamil 400 mg intravenous every 8 hours. For the remainder of the hospital stay, blood cultures were negative and white blood cell count was within normal limits. On day 20, the patient was discharged to a long-term care facility for continued ceftaroline treatment.

Discussion

The management of MRSA bacteremia remains challenging due to increasing antimicrobial resistance. Although the standard therapy for serious MRSA infections is vancomycin, treatment failures are becoming common in clinical practice due to increasing MICs (≥2 μg/mL). Other therapies may include daptomycin and off-label treatment with telavancin, quinupristin/dalfopristin, or ceftaroline fosamil. This report describes a patient with paravertebral abscess and MRSA bacteremia failing 3 days of vancomycin therapy due to MIC greater than or equal to 2 μg/mL and persistent bacteremia. Treatment with ceftaroline fosamil was well tolerated and resulted in continued clinical improvement. Based on this case report, ceftaroline fosamil may be a reasonable alternative for invasive MRSA infections.

Conclusions

This case report describes successful treatment of MRSA bacteremia with ceftaroline in a patient who responded poorly to conventional therapy, specifically vancomycin due to an elevated MIC (2 μg/mL).

Methicillin-resistant Staphylococcus aureus (MRSA) is a well-known gram-positive pathogen, causing infection in the hospital and community. Due to increasing prevalence of community-acquired cases, these 2 categories often overlap. MRSA bacteremia is often fatal and complications may be difficult to recognize, leading to increased risk of mortality. ¹ Traditionally, the treatment of choice for MRSA bacteremia has been vancomycin; however, recent reviews have reported that elevated vancomycin minimum inhibitory concentrations (MICs) commonly result in decreased efficacy and an increased probability of treatment failure, prompting the use of alternative agents.^2,3 Although daptomycin is an alternative, adverse effects (ie, elevations in serum creatine phosphokinase [CPK], drug-induced myopathy, peripheral neuropathy, and eosinophilic pneumonia) may limit its use in some patients.^1,4,5 The CPK elevation is dose dependent and is reversible once the dose is reduced or discontinued. Ceftaroline fosamil, a new fifth-generation cephalosporin, is US Food and Drug Administration (FDA) approved for the treatment of community-acquired pneumonia (CAP) and acute bacterial skin and skin-structure infections (ABSSSI).^6-8 Recent reports demonstrate the efficacy of ceftaroline fosamil for systemic MRSA infections such as bacteremia, endocarditis, and osteomyelitis.^4,9-11 This case report describes the successful treatment of MRSA bacteremia with ceftaroline fosamil.

Case Report

A 53-year-old, female (1.57 m [5 ft, 2 in] and 76.5 kg [169 lbs]) with a past medical history of cancer (unknown source/type) and hypothyroidism presented to the emergency department (ED) with complaints of neck pain and swelling following an injury 6 days prior. She reported a gradual increase in pain and swelling to the area. She further reported a sudden onset of paralysis to bilateral legs during transport. A computed tomography (CT) scan of the neck in the ED showed a posterior left paraspinal abscess, and magnetic resonance imaging (MRI) of the spine revealed possible spinal abscess and narrowing of the spinal canal. The patient was assessed by neurosurgery and was scheduled for emergent spinal cord decompression. After the procedure, she was admitted to the intensive care unit (ICU) for sepsis and suspected spinal shock. A complete blood count (CBC) drawn in the ICU revealed leukocytosis (white blood cell count [WBC] 24.3 × 10³/µL), and the patient had a temperature of 37.9°C (100.3°F). Empiric treatment was initiated with cefepime 2 g every 8 hours and vancomycin 1,250 mg (16.3 mg/ kg) every 12 hours targeting serum trough concentrations of 15 to 20 mg/L.

On hospital day 4, blood and wound cultures (drawn on day 1 in the ICU) grew MRSA listed as susceptible to vancomycin, but with an MIC of 2 µg/mL. Repeat blood cultures drawn on hospital day 2 were positive for Staphylococcus species. The infectious disease team was consulted for evaluation of possible endovascular infection/endocarditis. Due to the severity of the patient's condition, persistent bacteremia, and the high risk of vancomycin treatment failure given elevated MIC, therapy was converted to daptomycin 8 mg/kg/day (612 mg). Daptomycin therapy was continued on hospital days 5 to 15. Transesophageal echocardiogram did not identify any valvular vegetation. The patient reported progressive improvement in myelopathy and neck pain. Leukocytosis resolved during this time, and blood cultures performed on hospital day 7 were negative.

On hospital day 15, the patient developed acute kidney injury (AKI); her serum creatinine increased from 1.1 to 2.1 mg/dL over 24 hours (up 91%; BUN 27 mg/dL; BUN/SCr = 12.85), and urine output decreased abruptly (0.3 mL/kg/h). Nephrology was consulted and initially attributed AKI to daptomycin, which is a rare (2%-3%) adverse effect. Therapy was converted to ceftaroline 400 mg IV every 8 hours, accounting for the patient's renal function and the severity of infection. After additional work-up including renal ultrasound and review of other medications, nephrology ultimately attributed AKI to acute tubular necrosis (ATN) secondary to septic shock.

On hospital days 16 to 18, the patient's renal function improved slowly and WBC decreased. The dose of ceftaroline was increased to 600 mg intravenous every 8 hours on day 19 to account for the patient's improved renal function and persistent MRSA bacteremia. For the remainder of the hospital stay, blood cultures were negative and WBC was within normal limits. On day 20, patient was discharged to a long-term care facility for continued ceftaroline treatment.

Discussion

The management of serious MRSA infections remains challenging with currently available antibiotics. Although the standard therapy for MRSA infections has been vancomycin, increasing resistance patterns with an MIC 2 µg/mL or greater may result in vancomycin treatment failure and the need for new options.^2,3 Ceftaroline fosamil, a broad-spectrum cephalosporin, has bactericidal activity against MRSA.^6,7 Although the FDA indication of ceftaroline is limited to ABSSSI and CAP, recent case reports suggest efficacy in the treatment of serious MRSA infections such as bacteremia, endocarditis, and osteomyelitis.^4,9-11 Ceftaroline has proven to have good safety profile and lacks the serious toxicity of other anti-MRSA agents.

This case report describes a patient with paravertebral abscess and MRSA bacteremia failing 3 days of vancomycin therapy due to an MIC of 2 μg/mL. Treatment with ceftaroline fosamil was well tolerated and resulted in continued clinical improvement. A frequency of every 8 hours was used based on previous case reports and in vitro data.^4,12-14

It is important to note that this is a single case report and the patient received multiple MRSA-active agents prior to ceftaroline initiation. However, we hope that this single case report will prompt further evaluation on safety and efficacy of ceftaroline in the treatment of serious MRSA infections. The patient was transferred to a long-term acute care facility to complete an additional 6 weeks of antibiotic therapy and has not been seen in our institution since the discharge.