Successful Treatment of Ceftazidime‐Resistant Klebsiella pneumoniae Ventriculitis with Intravenous Meropenem and Intraventricular Polymyxin B: Case Report and Review

Segal‐Maurer, Sorana; Mariano, Noriel; Qavi, Abdul; Urban, Carl; Rahal, James J.

doi:10.1086/514754

Cited by 52 publications

(21 citation statements)

References 10 publications

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“…In nosocomial meningitis, meropenem should be regarded as the drug of choice. Intrathecal polymyxin B should also be considered, along with removal of neurosurgical hardware in cases of CSF shunt infections (361). Ertapenem shares the good in vitro activity of the other carbapenems (176).…”

Section: Antibiotic Choice For Serious Infectionsmentioning

confidence: 99%

Extended-Spectrum β-Lactamases: a Clinical Update

2005

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SUMMARY Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

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Section: Antibiotic Choice For Serious Infectionsmentioning

confidence: 99%

Extended-Spectrum β-Lactamases: a Clinical Update

2005

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“…While cure with intravenous colistimethate therapy alone has been documented (53, 77, 78, 96, 115), several reports noted failures with systemic therapy (8,22,50,133,183). Numerous case reports demonstrated successful outcomes with intraventricular or intrathecal instillation of colistimethate or polymyxin B in children (12,30,39,50,70,128,133,143,164,176,183) and adults (8,11,22,50,57,66,82,117,120,128,141,142,154,163,175,180,183) with or without corresponding intravenous therapy (Table 7). Given the fact that peak CSF levels of colistin approximate the MIC for most multidrug-resistant P. aeruginosa and A. baumannii strains (77,78), clinicians should have a low threshold for the administration of intrathecal or intraventricular therapy, especially if prompt improvement does not occur with intravenous therapy.…”

Section: Clinical and Microbiological Outcomesmentioning

confidence: 99%

Polymyxins Revisited

et al. 2008

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SUMMARY The global emergence of multidrug-resistant gram-negative bacilli has spurred a renewed interest in polymyxins. Once discarded due to concerns regarding nephrotoxicity and neurotoxicity, polymyxins now hold an important role in the antibiotic armamentarium. However, more reliable information is needed to determine the optimal dosing of these agents. Also, unanswered questions regarding in vitro testing remain, including questions regarding the reliability of automated systems and the establishment of appropriate breakpoints for defining susceptibility. Most contemporary clinical studies examining the use of these agents have involved patients with infections due to multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains. It has been reassuring that polymyxin therapy for resistant bacteria has resulted in clinical responses and toxicity rates similar to those for carbapenem therapy for susceptible isolates. While most surveillance studies demonstrated high rates of susceptibility, several reports noted the emergence of polymyxin-resistant nosocomial pathogens. Polymyxins have assumed an important antibiotic niche for therapy for hospital-acquired infections; further studies defining the optimal use of these agents will likely extend the duration of their clinical usefulness.

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“…Under the limited therapeutic options available to treat multidrug-resistant gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, polymyxins are sometimes the only available active antibiotics and have now become important therapeutic agents (13,25,28,29,55). Many recent reports have shown that patients infected with multidrug-resistant gram-negative pathogens improved upon treatment with polymyxins (19,27,44,48). In addition, polymyxins have been applied to prevent septic shock by removing circulating endotoxin to polystyrene fibers in an immobilized form (8).…”

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confidence: 99%

Identification of a Polymyxin Synthetase Gene Cluster of Paenibacillus polymyxa and Heterologous Expression of the Gene in Bacillus subtilis

Choi

Park

Kim³

et al. 2009

J Bacteriol

142

133

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Polymyxin, a long-known peptide antibiotic, has recently been reintroduced in clinical practice because it is sometimes the only available antibiotic for the treatment of multidrug-resistant gram-negative pathogenic bacteria. Lack of information on the biosynthetic genes of polymyxin, however, has limited the study of structure-function relationships and the development of improved polymyxins. During whole genome sequencing of Paenibacillus polymyxa E681, a plant growth-promoting rhizobacterium, we identified a gene cluster encoding polymyxin synthetase. Here, we report the complete sequence of the gene cluster and its function in polymyxin biosynthesis. The gene cluster spanning the 40.6-kb region consists of five open reading frames, designated pmxA, pmxB, pmxC, pmxD, and pmxE. The pmxC and pmxD genes are similar to genes that encode transport proteins, while pmxA, pmxB, and pmxE encode polymyxin synthetases. The insertional disruption of pmxE led to a loss of the ability to produce polymyxin. Introduction of the pmx gene cluster into the amyE locus of the Bacillus subtilis chromosome resulted in the production of polymyxin in the presence of extracellularly added L-2,4-diaminobutyric acid. Taken together, our findings demonstrate that the pmx gene cluster is responsible for polymyxin biosynthesis.

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Successful Treatment of Ceftazidime‐Resistant Klebsiella pneumoniae Ventriculitis with Intravenous Meropenem and Intraventricular Polymyxin B: Case Report and Review

Cited by 52 publications

References 10 publications

Extended-Spectrum β-Lactamases: a Clinical Update

Extended-Spectrum β-Lactamases: a Clinical Update

Polymyxins Revisited

Identification of a Polymyxin Synthetase Gene Cluster of Paenibacillus polymyxa and Heterologous Expression of the Gene in Bacillus subtilis

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