Risk factors for KPC-producing Klebsiella pneumoniae bacteremia

Tuon, Felipe Francisco; Rocha, Jaime L.; Toledo, Paula Virginia Michelon; Arend, Lavinia Nery Villa Stangler; Dias, Camila; Leite, Talita M.; Penteado-Filho, Sergio Ricardo; Pilonetto, Marcelo; Zavascki, Alexandre Prehn

doi:10.1016/j.bjid.2012.08.006

Cited by 50 publications

(47 citation statements)

References 10 publications

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“…Monotherapies did not present the same efficacy observed in the better performing combinations, PMBϩTIG and PMBϩTIGϩMER, corroborating previous studies, which observed lowered mortality with antimicrobial combinations (4)(5)(6)(7)(8)(9). It has been previously described, in retrospective data, that triple therapy might lower mortality in patients infected with KPC-producing K. pneumoniae; however, the MER MIC was not mentioned (4).…”

supporting

confidence: 84%

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Activity of Antimicrobial Combinations against KPC-2-Producing Klebsiella pneumoniae in a Rat Model and Time-Kill Assay

Toledo

Aranha

Arend³

et al. 2015

Antimicrob Agents Chemother

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f This study evaluated the efficacy of tigecycline (TIG), polymyxin B (PMB), and meropenem (MER) in 80 rats challenged with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae infection. A time-kill assay was performed with the same strain. Triple therapy and PMB؉TIG were synergistic, promoted 100% survival, and produced negative peritoneal cultures, while MER؉TIG showed lower survival and higher culture positivity than other regimens (P ‫؍‬ 0.018) and was antagonistic. In vivo and in vitro studies showed that combined regimens, except MER؉TIG, were more effective than monotherapies for this KPC-producing strain. Infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with therapeutic failure and increased mortality (1-5). It has been suggested that antibiotic combination might be a better alternative compared to monotherapy for treatment of KPC-producing isolates (4-9); however, further investigation on this therapeutic strategy is required (10, 11).In the present study, we evaluated the efficacy of regimes for a KPC-producing K. pneumoniae strain in an experimental model of systemic infection and in a time-kill assay (TKA).A KPC-producing K. pneumoniae strain, coded RM-1209, was isolated from a patient's blood and identified by Vitek 2 (bioMérieux, Craponne, France) in 2012. Antibiotic MICs were determined by agar dilution and interpreted according to CLSI and EUCAST for tigecycline (TIG) (12, 13). The strain presented MICs of Ͼ32 mg/liter, 1 mg/liter, and 0.5 mg/liter for meropenem (MER), tigecycline, and polymyxin B (PMB), respectively. Detection of the bla KPC gene was performed with BigDye v1.1 Sequencing kits (Applied Biosystems, Foster City, CA, USA), and KPC-2 was confirmed at databases queried by NCBI BLAST (6).The study was approved by the ethical committee, according to the Protocol for the Protection and Welfare of Animals (European Union). The animal model has been previously described (13). In brief, male and female immunocompetent Wistar rats weighing between 190 and 300 g were randomized into each treatment group. Absence of immunosuppression demanded administration of highly concentrated inoculums with 1.5 ϫ 10 10 CFU/ml. This solution, when diluted 1:20 presents an absorbance of 0.546 at 625 nm wavelength on spectrophotometry (corresponding to tube 50 of nephelometric scale). Seven groups of 10 rats were treated with the following regimens: MER, TIG, PMB, MERϩPMB, MERϩTIG, PMBϩTIG, or PMBϩMERϩTIG. Ten rats were untreated (control group). The sample size (80 rats) was calculated using the formula n ϭ z2PQ/d2 based on the expected proportion of deaths (50%) and 8% standard error with an 80% statistical power.Animals were injected with a 0.7-ml intraperitoneal aliquot of 1.5 ϫ 10 10 CFU/ml KPC-producing K. pneumoniae inoculum in the log growth state (14). After infection, rats received antimicrobials intraperitoneally, TIG (Tygacil) at 7 mg/kg of body weight every 12 h (15, 16), PMB (polymyxin B) at 2 mg/kg every 12 h (17, 18), or MER ...

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supporting

confidence: 84%

“…The strain presented MICs of Ͼ32 mg/liter, 1 mg/liter, and 0.5 mg/liter for meropenem (MER), tigecycline, and polymyxin B (PMB), respectively. Detection of the bla KPC gene was performed with BigDye v1.1 Sequencing kits (Applied Biosystems, Foster City, CA, USA), and KPC-2 was confirmed at databases queried by NCBI BLAST (6).…”

mentioning

confidence: 99%

Activity of Antimicrobial Combinations against KPC-2-Producing Klebsiella pneumoniae in a Rat Model and Time-Kill Assay

Toledo

Aranha

Arend³

et al. 2015

Antimicrob Agents Chemother

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“…Recent fluoroquinolone therapy was linked to KPCKP isolation in two earlier studies (19,20); notably, the presence of low-level fluoroquinolone resistance and carbapenem resistance genes (qnrB and bla KPC-2 , respectively) has been demonstrated on the same conjugative plasmid in K. pneumoniae isolates (20,29). Prolonged treatment with fluoroquinolones could also promote the selection of KPCKP strains by eliminating susceptible competing clones of K. pneumoniae.…”

Section: Discussionmentioning

confidence: 99%

“…A recent review of these efforts found that the factors associated with colonization, infection, and mortality caused by these organisms vary considerably with the species and enzymatic profile of the isolate (5). Less attention has been focused specifically on KPCproducing strains of K. pneumoniae (KPCKP), and these studies have also been fairly small (17)(18)(19)(20). The reported rates of mortality related to KPCKP infections vary widely, from 22% to 72% (3,4,7,21).…”

mentioning

confidence: 99%

Predictive Models for Identification of Hospitalized Patients Harboring KPC-Producing Klebsiella pneumoniae

Tumbarello

Trecarichi

Tumietto

et al. 2014

Antimicrob Agents Chemother

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The production of Klebsiella pneumoniae carbapenemases (KPCs) by Enterobacteriaceae has become a significant problem in recent years. To identify factors that could predict isolation of KPC-producing K. pneumoniae (KPCKP) in clinical samples from hospitalized patients, we conducted a retrospective, matched (1:2) case-control study in five large Italian hospitals. The case cohort consisted of adult inpatients whose hospital stay included at least one documented isolation of a KPCKP strain from a clinical specimen. For each case enrolled, we randomly selected two matched controls with no KPCKP-positive cultures of any type during their hospitalization. Matching involved hospital, ward, and month/year of admission, as well as time at risk for KPCKP isolation. A subgroup analysis was also carried out to identify risk factors specifically associated with true KPCKP infection. Since 2010, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have caused numerous outbreaks of severe nosocomial infections in the northeastern United States, Israel, Greece, and Italy, and they are now considered endemic in these areas (1-9). Not only do KPC-producing organisms hydrolyze carbapenems, but also, they are often resistant to multiple other antibiotics (7, 9-11). Consequently, they are invariably associated with high treatment failure rates (3, 4, 7).Several relatively small studies have investigated risk factors for infection and/or colonization by carbapenem-resistant isolates of K. pneumoniae and other Gram-negative bacteria (5,8,(12)(13)(14)(15)(16). A recent review of these efforts found that the factors associated with colonization, infection, and mortality caused by these organisms vary considerably with the species and enzymatic profile of the isolate (5). Less attention has been focused specifically on KPCproducing strains of K. pneumoniae (KPCKP), and these studies have also been fairly small (17)(18)(19)(20). The reported rates of mortality related to KPCKP infections vary widely, from 22% to 72% (3,4,7,21). The risk obviously depends on factors like population age and underlying disease/comorbidity profiles, which were highly heterogeneous in the studies cited above. The criteria used to distinguish true KPCKP infections and simple colonization can also influence mortality rates. The term "infection" is frequently applied to cases characterized by isolation of KPCKP from clinical specimens (rather than rectal swabs collected for screening purposes). However, the presence of KPCKP in such samples-especially sputum and urine-can also reflect simple colonization. Therefore, this definition can favor overtreatment and distorts assessments of clinical outcomes.To clarify the inpatient risk factors associated with isolation of a KPCKP strain, we conducted a large, retrospective study in five Italian hospitals, where these organisms are an increasingly frequent cause of serious disease. A subgroup analysis was also carried out to identify risk factors specifically associated with true KPCKP infection. MAT...

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“…Infections caused by KPC-or MBL-producing K. pneumoniae have been associated with severity of underlying disease, age, diabetes mellitus, ICU admission, mechanical ventilation, and exposure to cephalosporins, carbapenems, and fluoroquinolones [Gasink et al 2009;Hussein et al 2009;Moloudi et al 2010;Zarkotou et al 2010;Chitnis et al 2012;Tuon et al 2012].…”

Section: Individual Risk Factorsmentioning

confidence: 99%

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

Delgado-Valverde

Sojo-Dorado

Pascual

2013

Therapeutic Advances in Infection

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Enterobacteriaceae showing resistance to cephalosporins due to extended-spectrum b-lactamases (ESBLs) or plasmid-mediated AmpC enzymes, and those producing carbapenemases have spread worldwide during the last decades. Many of these isolates are also resistant to other first-line agents such as fluoroquinolones or aminoglycosides, leaving few available options for therapy. Thus, older drugs such as colistin and fosfomycin are being increasingly used. Infections caused by these bacteria are associated with increased morbidity and mortality compared with those caused by their susceptible counterparts. Most of the evidence supporting the present recommendations is from in vitro data, animal studies, and observational studies. While carbapenems are considered the drugs of choice for ESBL and AmpC producers, recent data suggest that certain alternatives may be suitable for some types of infections. Combined therapy seems superior to monotherapy in the treatment of invasive infections caused by carbapenemase-producing Enterobacteriaceae. Optimization of dosage according to pharmacokinetics/pharmacodynamics data is important for the treatment of infections caused by isolates with borderline minimum inhibitory concentration due to lowlevel resistance mechanisms. The increasing frequency and the rapid spread of multidrug resistance among the Enterobacteriaceae is a true and complex public health problem. IntroductionThe traditional first-line available options for treating serious infections caused by enterobacteria include penicillins, cephalosporins, monobactams, carbapenems, fluorquinolones, and in certain situations, aminoglycosides. The frequency of resistance to these first-line agents has been rising worldwide during the last decades [Paterson 2006;Rhomberg and Jones 2009;Houghton et al. 2010;Nordmann, et al. 2011] and now reach high proportions in many areas of the world.

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Risk factors for KPC-producing Klebsiella pneumoniae bacteremia

Cited by 50 publications

References 10 publications

Activity of Antimicrobial Combinations against KPC-2-Producing Klebsiella pneumoniae in a Rat Model and Time-Kill Assay

Activity of Antimicrobial Combinations against KPC-2-Producing Klebsiella pneumoniae in a Rat Model and Time-Kill Assay

Predictive Models for Identification of Hospitalized Patients Harboring KPC-Producing Klebsiella pneumoniae

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

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