Gentamicin therapy for sepsis due to carbapenem-resistant and colistin-resistant Klebsiella pneumoniae

González-Padilla, Marcelino; Torre‐Cisneros, Julián; Rivera-Espinar, Francisco; Pontes-Moreno, Antonio; López-Cerero, Lorena; Pascual, A; Nátera, Clara; Castillo-Rodríguez, Miguel; Salcedo, Inmaculada; Rodríguez-López, Fernando; Rivero, Antonio; Rodríguez-Baño, Jesús

doi:10.1093/jac/dku432

Cited by 96 publications

(64 citation statements)

References 28 publications

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“…Included patients had been treated in Europe and Australia in the years 2013 to 2016. Fifteen patients came from a single hospital in Spain that had an outbreak of KPC-producing K. pneumoniae; the characteristics of this strain have been previously described (13). Thirty-six patients (94.7%) received CAZ-AVI as salvage therapy after treatment with other antibiotics had failed; in the other two patients, CAZ-AVI was the first antibiotic chosen because no other appropriate treatment was available.…”

Section: Resultsmentioning

confidence: 99%

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

Temkin

Torre‐Cisneros

Beović

et al. 2017

Antimicrob Agents Chemother

172

107

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Ceftazidime-avibactam (CAZ-AVI) is a recently approved ␤-lactam-␤-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twentyfive patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro. Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P ϭ 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenemresistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

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Section: Resultsmentioning

confidence: 99%

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

Temkin

Torre‐Cisneros

Beović

et al. 2017

Antimicrob Agents Chemother

172

107

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“…Aminoglycosides have been used with some clinical success either alone or in combination therapy to treat infections due to KPC producers (106). A recent report suggested better outcomes when gentamicin (as monotherapy or in combination with tigecycline) was used for colistin-resistant, KPC-producing K. pneumoniae (122). The side effects of aminoglycosides include nephrotoxicity, especially when they are used in combination with colistin.…”

Section: Treatment Of Infections Due To K Pneumoniae With Carbapenemmentioning

confidence: 99%

Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance

Pitout

Nordmann

Poirel

2015

Antimicrob Agents Chemother

701

569

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The management of infections due to Klebsiella pneumoniae has been complicated by the emergence of antimicrobial resistance, especially to carbapenems. Resistance to carbapenems in K. pneumoniae involves multiple mechanisms, including the production of carbapenemases (e.g., KPC, NDM, VIM, OXA-48-like), as well as alterations in outer membrane permeability mediated by the loss of porins and the upregulation of efflux systems. The latter two mechanisms are often combined with high levels of other types of ␤-lactamases (e.g., AmpC). K. pneumoniae sequence type 258 (ST258) emerged during the early to mid-2000s as an important human pathogen and has spread extensively throughout the world. ST258 comprises two distinct lineages, namely, clades I and II, and it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Incompatibility group F plasmids with bla KPC have contributed significantly to the success of ST258. The optimal treatment of infections due to carbapenemase-producing K. pneumoniae remains unknown. Some newer agents show promise for treating infections due to KPC producers; however, effective options for the treatment of NDM producers remain elusive.

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“…However, optimal treatment for infections caused by CRKP has not yet been defined (14). The present retrospective study involved 104 unique patients with bacteremia due to CRKP with overall mortality rate of 25%, which is substantially lower than the rates reported for CRKP in previous studies (11,15,16). Alternatively, the difference may be resulted from unrecognized confounding variables.…”

Section: Discussionmentioning

confidence: 90%

Retrospective analysis of fosfomycin combinational therapy for sepsis caused by carbapenem-resistant Klebsiella pneumoniae

Liao

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to compare the efficacy and safety of fosfomycin combinational therapy with other antibiotics for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This retrospective cohort study examined 104 cases of sepsis caused by CRKP occurring between January 2012 and November 2014 in Shanghai Tenth People's Hospital. Three categories of patient outcome were assessed: Survival/mortality, duration of intensive care unit stays and duration of medical ventilation. Univariate ordinal analyses were adopted to evaluate the correlations between outcome and treatment. A total of 104 patients with physician-diagnosed CRKP were involved in the study. The overall mortality rate was 25.0%. The majority of the infections (84; 80.8%) were hospital acquired. Critical infections received more than one active antibiotic as therapy. Patients treated with fosfomycin combinational therapy were less likely to fail therapy (OR: 4.71, 95% CI: 1.03-21.65, P=0.034) and tended to have a shorter duration of mechanical ventilation. Gender (OR: 4.35, 95% CI: 1.08-3.60, P= 0.037), history of chronic obstructive pulmonary disease (OR: 9.35, 95% CI: 0.06-0.19, P=0.007) and peripheral catheter use (OR: 3.00, 95% CI: 0.07-0.19, P=0.002) are risk factors for clinical outcome. Therefore, the use of fosfomycin combinational therapy for treatment of infection due to CRKP appears to be associated with improved survival rate.

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Gentamicin therapy for sepsis due to carbapenem-resistant and colistin-resistant Klebsiella pneumoniae

Abstract: Gentamicin reduced the mortality from sepsis caused by this K. pneumoniae ST512 clone producing KPC-3, SHV-11 and TEM-1.

Cited by 96 publications

References 28 publications

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance

Retrospective analysis of fosfomycin combinational therapy for sepsis caused by carbapenem-resistant Klebsiella pneumoniae

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