Treatment of Multidrug-Resistant Acinetobacter baumannii Meningitis with Ampicillin/Sulbactam

Me, Jiménez-Mejías; Pachón, Jerónimo; Becerril, Berta; Palomino-Nicás, J; Rodríguez-Cobacho, A.; Revuelta, Manuel

doi:10.1093/clinids/24.5.932

Cited by 98 publications

(44 citation statements)

References 26 publications

(38 reference statements)

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“…Small observational series have shown encouraging results with ampicillin-sulbactam for the treatment of nosocomial A. baumannii meningitis (268,328), a problematic entity of increasing significance. However, failures have been reported (268,328).…”

Section: Existing Antimicrobial Agentsmentioning

confidence: 99%

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Acinetobacter baumannii : Emergence of a Successful Pathogen

2008

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SUMMARY Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.

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Section: Existing Antimicrobial Agentsmentioning

confidence: 99%

“…However, failures have been reported (268,328). The cerebrospinal fluid (CSF) penetration of sulbactam in patients with inflamed meninges is reported to be 2 to 32% of serum levels (170), with peak serum levels reaching approximately 42 to 60 mg/liter after an intravenous (i.v.)…”

Section: Existing Antimicrobial Agentsmentioning

confidence: 99%

Acinetobacter baumannii : Emergence of a Successful Pathogen

2008

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“…Six patients with Acinetobacter baumannii meningitis were cured with systemic sulbactam (4 g/day) plus ampicillin, and two did not respond (99). For one adult treated with 1 g sulbactam every …”

Section: ␤-Lactam Antibioticsmentioning

confidence: 99%

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

2010

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SUMMARY The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.

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“…This Gram-negative, aerobic, coccobacillus is responsible for a significant number of hospital-acquired infections, including those of the skin and bloodstream, as well as pneumonia and meningitis (5,6,18,34,47). Importantly, A. baumannii is able to persist on hospital surfaces for weeks to months, providing an environmental reservoir for its transmission (44)(45)(46).…”

mentioning

confidence: 99%

Rapid Killing of Acinetobacter baumannii by Polymyxins Is Mediated by a Hydroxyl Radical Death Pathway

Sampson

Liu

Schroeder

et al. 2012

Antimicrob Agents Chemother

161

125

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Acinetobacter baumannii is an opportunistic pathogen that is a cause of clinically significant nosocomial infections. Increasingly, clinical isolates of A. baumannii are extensively resistant to numerous antibiotics, and the use of polymyxin antibiotics against these infections is often the final treatment option. Historically, the polymyxins have been thought to kill bacteria through membrane lysis. Here, we present an alternative mechanism based on data demonstrating that polymyxins induce rapid cell death through hydroxyl radical production. Supporting this notion, we found that inhibition of radical production delays the ability of polymyxins to kill A. baumannii. Notably, we demonstrate that this mechanism of killing occurs in multidrug-resistant clinical isolates of A. baumannii and that this response is not induced in a polymyxin-resistant isolate. This study is the first to demonstrate that polymyxins induce rapid killing of A. baumannii and other Gram-negatives through hydroxyl radical production. This significantly augments our understanding of the mechanism of polymyxin action, which is critical knowledge toward the development of adjunctive therapies, particularly given the increasing necessity for treatment with these antibiotics in the clinical setting.

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Treatment of Multidrug-Resistant Acinetobacter baumannii Meningitis with Ampicillin/Sulbactam

Cited by 98 publications

References 26 publications

Acinetobacter baumannii : Emergence of a Successful Pathogen

Acinetobacter baumannii : Emergence of a Successful Pathogen

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

Rapid Killing of Acinetobacter baumannii by Polymyxins Is Mediated by a Hydroxyl Radical Death Pathway

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