Successful treatment of ventriculitis caused by<i>Pseudomonas aeruginosa</i>and carbapenem-resistant<i>Klebsiella pneumoniae</i>with i.v. ceftazidime–avibactam and intrathecal amikacin

Gofman, Natalie; To, Kim; Whitman, Marc; Garcia-Morales, Edgar

doi:10.2146/ajhp170632

Cited by 28 publications

(19 citation statements)

References 25 publications

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“…Observed adverse effects were high-tone hearing impairment and transient vomiting (80). In a 66-year-old woman and a 32-year-old man, a daily dose of 30 mg was administered without severe side effects (81,82). Amikacin concentrations in CSF were not reported in the latter two patients.…”

Section: Aminoglycosidesmentioning

confidence: 96%

Intrathecal Antibacterial and Antifungal Therapies

2020

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SUMMARY Intrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure.

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Section: Aminoglycosidesmentioning

confidence: 96%

Intrathecal Antibacterial and Antifungal Therapies

2020

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“…Avibactam penetration in rabbit CSF is about 38% (16). Six case reports have described the successful use of intravenous ceftazidime/avibactam for the treatment of CNS infections caused by multidrug-resistant bacteria (17)(18)(19)(20)(21)(22). Even if obvious publication bias may preclude the identification of therapeutic failure of avibactamcontaining regimens for CNS infections, these data suggest that avibactam penetration in CSF is sufficient for in situ ␤-lactamase inhibition.…”

Section: Discussionmentioning

confidence: 98%

Inhibition Activity of Avibactam against Nocardia farcinica β-Lactamase FAR _IFM10152

Lebeaux

Ourghanlian

Dorchêne

et al. 2020

Antimicrob Agents Chemother

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Nocardia farcinica, one of the most frequent pathogenic species responsible for nocardiosis, is characterized by frequent brain involvement and resistance to β-lactams mediated by a class A β-lactamase. Kinetic parameters for hydrolysis of various β-lactams by FARIFM10152 from strain IFM 10152 were determined by spectrophotometry revealing a high catalytic activity (kcat/Km) for amoxicillin, aztreonam, and nitrocefin. For cephems, kcat/Km was lower but remained greater than 104 M−1 s−1. A low catalytic activity was observed for meropenem, imipenem, and ceftazidime hydrolysis. FARIFM10152 inhibition by avibactam and clavulanate was compared using nitrocefin as a reporter substrate. FARIFM10152 was efficaciously inhibited by avibactam with a carbamoylation rate constant (k2/Ki) of (1.7 ± 0.3) × 104 M−1 s−1. The 50% effective concentrations (EC50s) of avibactam and clavulanate were 0.060 ± 0.007 μM and 0.28 ± 0.06 μM, respectively. Amoxicillin, cefotaxime, imipenem, and meropenem MICs were measured for ten clinical strains in the presence of avibactam and clavulanate. At 4 μg/ml, avibactam and clavulanate restored amoxicillin susceptibility in all but one of the tested strains but had no effect on the MICs of cefotaxime, imipenem, and meropenem. At 0.4 μg/ml, amoxicillin susceptibility (MIC ≤ 8 μg/ml) was restored for 9 out of 10 strains by avibactam but only for 4 out of 10 strains by clavulanate. Together, these results indicate that avibactam was at least as potent as clavulanate, suggesting that the amoxicillin-avibactam combination could be considered as an option for the rescue treatment of N. farcinica infections if clavulanate cannot be used.

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“…In pooled isolates from five RCTs, there were 89.7 and 66.1% sensitivity to MDR Enterobacter cloacae (n = 29) and P. aeruginosa (n = 56), respectively, and a minimal decrease in MICs compared to ceftazidime alone for P. aeruginosa [75]. Case reports note success in using CZA to treat other types of infections, including ventriculitis and hardware-associated osteomyelitis, due to KPC and MBL producing K. pneumoniae or P. aeruginosa [11,14,18]. There are ongoing phase II studies for the treatment of febrile neutropenia and in the pediatric population.…”

Section: Ceftazidime/avibactammentioning

confidence: 99%

Antibiotics in the Pipeline for Treatment of Infections due to Gram-Negative Organisms

Vissichelli

Stevens

2019

Curr Treat Options Infect Dis

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Purpose of review We systematically review the literature on antibiotics approved by the Food and Drug Administration since 2015 or that are in development through phase III trials for the treatment of infections due to gram-negative organisms. Recent findings The crisis of antimicrobial resistance creates a dire need for the development of novel antimicrobials with enhanced activity against resistant bacteria. Of the agents that are currently in the pipeline or recently approved, few are from new classes and most represent modifications of preexisting agents. There continues to be a lack of treatment options especially for infections caused by organisms that produce metallo-βlactamases. Furthermore, there is a paucity of data investigating the efficacy of these new antimicrobials for treatment of infections due to multidrug-resistant organisms. Summary This review outlines the antimicrobials in development for the treatment of infections due to gram-negative bacteria. There are various agents in development that seem promising, but more studies are needed to evaluate the efficacy of these agents in treating infections, especially those due to multidrug-resistant organisms. The development of new antimicrobials is critical to combat the crisis of antimicrobial resistance.

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Successful treatment of ventriculitis caused byPseudomonas aeruginosaand carbapenem-resistantKlebsiella pneumoniaewith i.v. ceftazidime–avibactam and intrathecal amikacin

Abstract: A man with ventriculitis caused by and carbapenem-resistant was successfully treated with i.v. ceftazidime-avibactam and intrathecal amikacin.

Cited by 28 publications

References 25 publications

Intrathecal Antibacterial and Antifungal Therapies

Intrathecal Antibacterial and Antifungal Therapies

Inhibition Activity of Avibactam against Nocardia farcinica β-Lactamase FAR _IFM10152

Antibiotics in the Pipeline for Treatment of Infections due to Gram-Negative Organisms

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Successful treatment of ventriculitis caused byPseudomonas aeruginosaand carbapenem-resistantKlebsiella pneumoniaewith i.v. ceftazidime–avibactam and intrathecal amikacin

Abstract: A man with ventriculitis caused by and carbapenem-resistant was successfully treated with i.v. ceftazidime-avibactam and intrathecal amikacin.

Cited by 28 publications

References 25 publications

Intrathecal Antibacterial and Antifungal Therapies

Intrathecal Antibacterial and Antifungal Therapies

Inhibition Activity of Avibactam against Nocardia farcinica β-Lactamase FAR IFM10152

Antibiotics in the Pipeline for Treatment of Infections due to Gram-Negative Organisms

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Product

Resources

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Inhibition Activity of Avibactam against Nocardia farcinica β-Lactamase FAR _IFM10152