Successful treatment of Acinetobacter meningitis with meropenem and rifampicin

Todd Gleeson1,*, Kyle Petersen1 and John Mascola2

1 Department of Infectious Diseases, National Naval Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889–5600, USA; 2 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA


* Corresponding author. Tel: +1-301-319-8360; Fax: +1-301-295-2992; E-mail: tdgleeson{at}bethesda.med.navy.mil

Keywords: nosocomial meningitis , post-neurosurgical meningitis , ventriculostomy

Sir,

Acinetobacter calcoaceticus-baumannii complex is a common cause of nosocomial infections, including post-neurosurgical meningitis. Multidrug-resistant (MDR) Acinetobacter is increasingly common worldwide, presenting a therapeutic challenge. Non-traditional antibiotics, including sulbactam, colistin and polymyxin B, have been used for MDR Acinetobacter meningitis.

Rifampicin demonstrates a bactericidal effect against Acinetobacter baumannii both in vitro as well as in animal models. Rifampicin monotherapy for MDR Acinetobacter pneumonia in a mouse model achieves a superior survival rate (94%) to other antibiotics1 and has superior bactericidal activity to colistin.2 Rifampicin is also additive or synergistic with sulbactam against MDR A. baumannii,3 and with carbapenems for Pseudomonas aeruginosa, Serratia marcescens and Enterobacter species.4 To our knowledge, this is the first published report of the use of rifampicin in Acinetobacter meningitis in humans. We describe our use of rifampicin, in combination with meropenem, in the treatment of post-neurosurgical Acinetobacter meningitis.

A 34-year-old female suffered a subarachnoid haemorrhage while on military service in Iraq and underwent emergency ventriculostomy in Kuwait 18 days prior to admission to our hospital. She was transferred after coiling of two intracranial aneurysms and replacement of the ventriculostomy. On arrival, she was receiving vancomycin for ventriculostomy prophylaxis and phenytoin for seizure prophylaxis. Cerebrospinal fluid (CSF) at admission was normal. On hospital day 7, she developed fever and became obtunded. Gram staining of the CSF demonstrated Gram-negative coccobacilli. Culture of the CSF grew both A. calcoaceticus-baumannii complex and Enterobacter aerogenes. Blood cultures also grew Acinetobacter. Antibiotic susceptibility testing by Vitek revealed both Acinetobacter isolates were susceptible to imipenem, ticarcillin/clavulanic acid and ampicillin/sulbactam. Meropenem, gentamicin and metronidazole were empirically added to the vancomycin. The ventriculostomy was required for increased intracranial pressure and was replaced at an adjacent site. On day 9 the patient remained febrile and obtunded. CSF cultures grew A. calcoaceticus-baumannii resistant to ampicillin/sulbactam, ceftazidime, ceftriaxone, gentamicin, imipenem, piperacillin/tazobactam, tobramycin and trimethoprim/sulfamethoxazole, with intermediate susceptibility to ticarcillin/clavulanic acid.

On hospital days 11 and 13 the CSF Gram stains and cultures demonstrated persistent Acinetobacter, with susceptibility to imipenem, ampicillin/sulbactam and ticarcillin/clavulanic acid. Rifampicin susceptibility testing by disc diffusion (5 µg disc on Mueller–Hinton agar with a 0.5 McFarland inoculum incubated for 24 h at 32–36°C in ambient air) revealed an 11 mm zone of inhibition. On hospital day 13, rifampicin at a dose of 600 mg intravenously daily was added to the meropenem, and gentamicin and metronidazole were stopped. On hospital day 16, the patient defervesced, and CSF analysis demonstrated marked improvement with negative cultures (Table 1). Rifampicin and meropenem were continued for 2 more weeks. The ventriculostomy was removed on hospital day 23. The patient was discharged from the hospital ambulating with minimal assistance 30 days after admission.


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Table 1. Antibiotic use and cerebrospinal fluid culture and laboratory results

 
Nosocomial meningitis due to A. calcoaceticus-baumannii complex carries a 20–25% mortality.5 Acinetobacter may be resistant to multiple antibiotics at the time of initial infection, or may rapidly develop resistance during therapy. Susceptibility testing by rapid automated systems, such as the Vitek system in use at our hospital, may erroneously report resistance in Acinetobacter species.6 This is one potential explanation for the MDR Acinetobacter isolated on hospital day 9 in our patient. We made the decision to add rifampicin based on our patient's unimproved clinical status and believe that rifampicin in combination with meropenem provided a cure of meningitis due to Acinetobacter in this patient. Additional in vitro, animal and clinical studies of rifampicin and carbapenem combinations for Acinetobacter are necessary.

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All authors: no conflicts.

References

1. Wolff M, Joly-Guillou M, Farinotti R et al. In vivo efficacies of combinations of ß-lactams, ß-lactamase inhibitors, and rifampin against Acinetobacter baumannii in a mouse pneumonia model. Antimicrob Agents Chemother 1999; 43: 1406–11.[Abstract/Free Full Text]

2. Montero A, Ariza J, Corbella X et al. Efficacy of colistin versus ß-lactams, aminoglycosides, and rifampin as monotherapy in a mouse model of pneumonia caused by multiresistant Acinetobacter baumannii. Antimicrob Agents Chemother 2002; 46: 1946–52.[CrossRef]

3. Appleman M, Belzberg H, Citron D et al. In vitro activities of nontraditional antimicrobials against multiresistant Acinetobacter baumannii strains isolated in an intensive care unit outbreak. Antimicrob Agents Chemother 2000; 44: 1035–40.[Abstract/Free Full Text]

4. Chin NX, Neu HC. Synergy of imipenem—a novel carbapenem, and rifampin and ciprofloxacin against Pseudomonas aeruginosa, Serratia marcescens and Enterobacter species. Chemotherapy 1987; 33: 183–8.[ISI][Medline]

5. Siegman-Igra Y, Bar-Yosef S, Gorea A et al. Nosocomial Acinetobacter meningitis secondary to invasive procedures: report of 25 cases and review. Clin Infect Dis 1997; 24: 932–5.[ISI][Medline]

6. Tsakris A, Pantazi A, Pournaras S et al. Pseudo-outbreak of imipenem-resistant Acinetobacter baumannii resulting from false susceptibility testing by a rapid automated system. J Clin Micro 2000; 38: 3505–7.[Abstract/Free Full Text]





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