TY - JOUR
AU - Joshi,, Prajwol
AB - Abstract Purpose A case of a patient who received ceftaroline fosamil as salvage therapy for a methicillin-resistant Staphylococcus aureus (MRSA) epidural abscess is reported. Summary A 48-year-old white woman arrived at the emergency department (ED) with an altered mental status. She had been to the ED two days prior with complaints of sudden-onset and worsening neck pain. She had a history of compacted disks in her neck secondary to a motor vehicle accident that occurred three years prior but that did not require surgical intervention. Computed tomography and magnetic resonance imaging scans confirmed an epidural abscess with wound cultures growing MRSA. The admitting physician indicated that the patient was severely septic. Acyclovir, ceftriaxone, and vancomycin were initiated for empirical treatment due to suspected meningitis. Paired blood cultures also continued to grow MRSA in four of four bottles collected four days after admission. This indicated that antimicrobial therapy was not successfully eradicating the MRSA found in the blood and the patient’s clinical status was deteriorating. Ceftaroline was used as salvage therapy, resulting in rapid clearance of MRSA from the blood and the patient becoming afebrile in 24 hours. Blood culture tests on hospital day 11—one day after ceftaroline initiation—were clear of MRSA. The patient was discharged to a long-term-care facility and ordered ceftaroline fosamil 600 mg i.v. every 12 hours for four weeks. Conclusion A MRSA epidural abscess in a 48-year-old woman was successfully treated with ceftaroline fosamil 600 mg every 12 hours as salvage therapy. Treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections is a challenge in patients who do not respond to treatment or are intolerant to standard therapies such as vancomycin, linezolid, and daptomycin. Although the use of ceftaroline fosamil for the treatment of deep-seated MRSA infections has been documented,1,2 the effectiveness of ceftaroline for MRSA infections in the central nervous system (CNS) has not been described. Currently, ceftaroline is approved by the Food and Drug Administration only for the treatment of community-acquired pneumonia and complicated skin and skin-structure infections.3,4 Unlike standard treatments that have failed in the treatment of severe MRSA infections such as endocarditis, pneumonia, and osteomyelitis, ceftaroline has demonstrated clinical and microbiological successes.1,2 Dosing for ceftaroline in these off-label indications has deviated from the typical dose of 600 mg i.v. every 12 hours to 600 mg i.v. every 8 hours due to its short half-life of 1.6 hours.1, 2, 5 We report the case of a patient in whom ceftaroline was used to treat a MRSA infection associated with an epidural abscess. Case report A 48-year-old white woman arrived at the emergency department (ED) with an altered mental status. The patient was found unconscious at her house for an unspecified time. She had been to the ED two days prior with complaints of sudden-onset and worsening neck pain. The patient indicated that the pain spanned from her right shoulder to her upper back. She had a history of compacted disks in her neck secondary to a motor vehicle accident that occurred three years prior but that did not require surgical intervention. No fever was noted at the prior ED visit, and the patient was discharged with pain medications (oxycodone hydrochloride 5 mg–acetaminophen 325 mg orally every four hours as needed for pain and diazepam 10 mg orally every eight hours as needed for muscle spasm) and a plan to follow up with her primary care physician. Her surgical history included open reduction internal fixation on the left side of her pelvis after the previously mentioned motor vehicle accident. During her initial workup for this visit, she was found to be febrile and agitated. Her medical history was unremarkable. She was an active smoker and denied any history of i.v. drug abuse. Her home medications included cyclobenzaprine hydrochloride 10 mg orally thrice daily as needed. The patient’s chief complaint involved pain in her right shoulder, upper back, and neck that she rated a 10 on a scale of 1 to 10. The patient met three of four systemic inflammatory response syndrome (SIRS) criteria: respiratory rate of 37 breaths/min, heart rate of 129 beats/min, white blood cell (WBC) count of 8.6 × 103 cells/μL (normal range, 4–11.1 × 103 cells/μL), and a temperature of 102.3 °F. The admitting physician indicated that the patient was severely septic based on the SIRS criteria, a platelet count of 59 × 103 cells/μL (normal range, 150–450 × 103 cells/ μL), and her altered mental status. A complete blood count with differential revealed the following in addition to the WBC count: bands, 4% (normal range, 0–6%); neutrophils, 86% (normal range, 32–75%); and lymphocytes, 6% (normal range, 12–49%). In the ED, the patient was started on acyclovir 550 mg every 8 hours, ceftriaxone 2 g every 12 hours, and vancomycin for empirical treatment due to suspected meningitis. The patient was given a loading dose of vancomycin 1 g and then given vancomycin 650 mg every 8 hours for a projected trough of 18 μg/mL. A 1-L bolus dose of 0.9% sodium chloride injection was also administered in the ED. No vasopressor therapy was started, as the patient’s mean arterial pressure was 83 mm Hg. Early analysis of the cerebrospinal fluid (CSF) revealed the following: red blood cells, 16 cells/mm3 (normal, 0 cells/mm3); WBCs, 591 cells/mm3; protein, >250 mg/dL (normal range, 15–45 mg/dL); and glucose, 54 mg/dL (normal range, 40–70 mg/dL). The CSF differential included 97% segmented neutrophils and 3% monocytes. The patient’s weight and height were 55.3 kg and 161 cm, respectively, yielding a body mass index of 21.3 kg/m2. The admitting physician requested a consultation with an infectious diseases physician. Multiple attempts were made to obtain CSF. Due to the combination of a bloody sample, lack of clinical findings, and a negative CSF culture, meningitis was not likely. Paired blood cultures from the emergency room grew MRSA in four of four bottles, indicating a high-grade bacteremia and the possibility of an underlying infection. A computed tomography (CT) scan, conducted on hospital day 3, confirmed the suspicion of a paraspinal abscess, showing fluid collection in the paraspinal deep intrinsic muscles of the right neck. According to the radiology report, the abscess contained an air bubble measuring approximately 6 × 4 × 2 cm and appeared multiloculated. An early epidural intraspinal extension was difficult to exclude by the radiologist. The results of magnetic resonance imaging (MRI), performed on hospital day 4, showed extensive dorsal epidural abscess collection extending from C4–5 disk space to the midbody of T5. Another soft-tissue abscess collection was identified in the right posterior lateral neck soft tissues of the right C3–4 and C4–5 facets. One day later, another MRI of the lumbar region revealed an abscess located from the L3–4 space to the L5–S1 space. Osteomyelitis was not evident from the MRI report. On hospital day 5, the patient underwent emergent incision and drainage of a continuous spinal epidural abscess, C3–T6 decompression, and fusion of C2–T7, along with L4–5 decompression. A separate abscess was found at L4–S1. Based on the culture, CT, and MRI results, ceftriaxone and acyclovir were discontinued, and monotherapy with vancomycin was continued. Cultures from the spinal abscesses obtained during the laminectomy on hospital day 5 confirmed MRSA with vancomycin and daptomycin minimum inhibitory concentrations (MICs) of 2 and 1 μg/mL, respectively. All susceptibilities were obtained through microdilution using Microscan (Siemens Healthcare Diagnostics, Deerfield, IL) unless otherwise noted. Paired blood cultures also continued to grow MRSA in four of four bottles collected four days after admission. This indicated that antimicrobial therapy was not successfully eradicating the MRSA found in the blood and the patient’s clinical status was deteriorating. Due to the presence of persistent bacteremia, a transesophageal echocardiogram was ordered on hospital day 15, which showed mild mitral valve regurgitation and no vegetation. After four days of vancomycin therapy with an inadequate response, a decision was made to switch to daptomycin 6 mg/kg every 24 hours. The decision to use daptomycin was based on the MIC of vancomycin for MRSA and the patient’s lack of clinical response. Increasing evidence suggests that a vancomycin MIC of 2 μg/mL is associated with a higher risk of treatment failure in MRSA infections.6 Incision and drainage occurred one day after the start of daptomycin. Seven days after the initiation of daptomycin, the patient was still febrile (101.3 °F) and had multiple MRSA-positive blood cultures. At this point, daptomycin was discontinued and ceftaroline fosamil 600 mg i.v. every 12 hours was started as salvage therapy. Before discontinuing daptomycin, an Etest (AB bioMérieux, Durham, NC) was performed to determine the susceptibilities for daptomycin (0.38 μg/mL), vancomycin (1.5 μg/mL), and ceftaroline (0.5 μg/mL). Lin ezolid was not an option due to a drug interaction with cyclobenzaprine, a serotonergic agent. Blood culture tests on hospital day 11—one day after ceftaroline initiation— were clear of MRSA, and the patient became afebrile (98.8 °F). The patient was discharged to a long-term-care facility and ordered ceftaroline fosamil 600 mg i.v. every 12 hours for four weeks. Before her discharge, the patient’s thrombocytopenia resolved (377 × 103 cells/μL) with antibiotic therapy. Discussion In this case, the treatment standard for MRSA infections included vancomycin. According to the MRSA treatment guidelines issued by the Infectious Diseases Society of America (IDSA), vancomycin or daptomycin is the drug of choice in patients with bacteremia.7 Furthermore, the guidelines encourage treatment durations of four to six weeks in patients whose blood cultures are not clear of MRSA within 72 hours. Vancomycin dosing was calculated using the hospital’s dosing protocol, which projected a trough of 18 μg/mL. The only trough value obtained for vancomycin was 9 μg/mL, with needed therapeutic levels of 15–20 μg/mL. While vancomycin therapy never reached therapeutic levels, a switch to daptomycin was needed based on an MIC for vancomycin of 2 μg/mL as well as a lack in clinical improvement. When determining susceptibilities to antimicrobials, variation can occur depending on the testing method used. Microscan tends to overestimate some susceptibility results, yielding higher MICs.8 In this case, clinicians followed IDSA MRSA guidelines by requesting Etesting in patients not responding to therapy with a vancomycin MIC of 2 μg/mL.7 Etesting uses disk diffusion as opposed to microdilution and is more accurate for determining the presence of heteroresistant vancomycin intermediate S. aureus.8 The addition of rifampin to vancomycin is also an option for patients with epidural abscesses as an add-on therapy,7 though evidence supporting this recommendation is limited. While daptomycin was a reasonable first- or second-line choice, a dose of 8–10 mg/kg may be required for severe bacteremia.7 Daptomycin is effective for clearing bacteremia but is not a recommended agent for the treatment of epidural abscesses,7 as it has poor penetration (11.5%) into the CNS.9 While CNS penetration is poor, one case series demonstrated the effectiveness of daptomycin 6–8 mg/kg in treating spinal infections.10 In this case, blood cultures were positive for MRSA during treatment with daptomycin, so ceftaroline fosamil 600 mg every 12 hours was used as salvage therapy. The penetration of ceftaroline into CSF has been documented to be 15% in rabbit models.11 While ceftaroline’s penetration into CSF is poor, human data are lacking. While the epidural space is highly lipophilic, it may directly connect with the vasculature system, allowing drugs to penetrate more easily than in other CNS infections.12 Linezolid, however, has excellent CNS penetration (30–70%).13 Even with effective CNS penetration, many other factors, including drug interactions, efficacy, and adverse effects, must be considered before using linezolid. Our patient was taking one serotonergic agent, cyclobenzaprine, which could cause serotonergic and adrenergic toxicities if used with linezolid. Based on the mechanism of action involving monoamine oxidase inhibition of linezolid combined with the serotonin and nor-epinephrine reuptake inhibition by cyclobenzaprine, these toxicities are real concerns.14,15 Linezolid remains a second-line option for patients with bacteremia who do not respond to or are intolerant of vancomycin and daptomycin.16 Without any evidence for CNS treatment of MRSA infections with ceftaroline, little guidance regarding its efficacy and dosing was available. While there is no guidance for ceftaroline dosing for the treatment of epidural abscesses, limited case series have described administration of the drug every 8 hours in other deep-seated infections.1,2 Caution should be used when interpreting data from these case series, as the sample populations were small. The dosing interval for this patient was every 12 hours, which was appropriate for an average-size patient who may not require more-frequent administration. This dosing interval quickly cleared MRSA from the patient’s blood cultures. This case highlights the difficult nature of treating MRSA infections, especially deep-seated infections. Epidural abscesses are associated with a mortality rate of 5–20%, with poorer outcomes associated with MRSA infections.17 When S. aureus is resistant to vancomycin, treatment options are limited. The main remaining treatment options include linezolid and daptomycin, and some patients do not respond to these or are unable to tolerate them. More studies are needed to provide evidence for the efficacy of ceftaroline for the treatment of CNS infections. Conclusion A MRSA epidural abscess in a 48-year-old woman was successfully treated with ceftaroline fosamil 600 mg every 12 hours as salvage therapy. Footnotes The authors have declared no potential conflicts of interest. References 1 Lin J Aung G Thomas A et al. . 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Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection . Clin Infect Dis . 2010 ; 51 : 641 – 50 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Zhanel G Sniezek G Schweizer F et al. . Ceftaroline: a novel broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus . Drugs . 2009 ; 69 : 809 – 31 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Van Hal SG Lodise TP Paterson DL . The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus: a systematic review and meta-analysis . Clin Infect Dis . 2012 ; 54 : 755 – 71 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Liu C Bayer A Cosgrove SE et al. . Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children . Clin Infect Dis . 2011 ; 52 : e18 – 55 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Swenson JM Anderson KF Lonsway DR et al. . Accuracy of commercial and reference susceptibility testing methods for detecting vancomycin-intermediate Staphylococcus aureus . J Clin Microbiol . 2009 ; 47 : 2013 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Kullar R Chin J Edwards D et al. . Pharmacokinetics of single-dose daptomycin in patients with suspected or confirmed neurological infections . Antimicrob Agents Chemother . 2011 ; 55 : 3505 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Burdette SD . Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine . Spine J . 2009 ; 9 : e5 – 8 . 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Google Scholar Crossref Search ADS PubMed WorldCat 15 Cosgrove S Fowler VG . Management of methicillin-resistant Staphylococcus aureus bacteremia . Clin Infect Dis . 2008 ; 46 ( suppl 5 ): S386 – 93 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Park HJ Kim SH Kim MJ et al. . Efficacy of linezolid-based salvage therapy compared with glycopeptide-based therapy in patients with persistent methicillin-resistant Staphylococcus aureus bacteremia . J Infect . 2012 ; 65 : 505 – 12 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Pradila G Nagahama Y Spivak AM et al. . Spinal epidural abscess: current diagnosis and management . Curr Infect Dis Rep . 2010 ; 12 : 484 – 91 . Google Scholar Crossref Search ADS PubMed WorldCat Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
TI - Methicillin-resistant Staphylococcus aureus epidural abscess treated with ceftaroline fosamil salvage therapy
JF - American Journal of Health-System Pharmacy
DO - 10.2146/ajhp130246
DA - 2014-01-15
UR - https://www.deepdyve.com/lp/oxford-university-press/methicillin-resistant-staphylococcus-aureus-epidural-abscess-treated-mtKfS1hndr
SP - 110
VL - 71
IS - 2
DP - DeepDyve
ER -