Activity of ceftazidime-avibactam against carbapenemase-producing Enterobacteriaceae from urine specimens obtained during the infection-carbapenem resistance evaluation surveillance trial (iCREST) in Spain

García-Castillo, María; García‐Fernández, Sergio; Gómez-Gil, Rosa; Pitart, Cristina; Oviaño, Marina; Gracia-Ahufinger, Irene; Díaz-Regañón, Jazmín; Tato, Marta; Cantón, Rafael

doi:10.1016/j.ijantimicag.2018.01.011

Cited by 30 publications

(24 citation statements)

References 18 publications

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“…Indeed, ceftazidimeavibactam inhibits KPC and OXA-48 enzymes, but it is not active against the metallo-b-lactamases (ECDC EARS-NET report, 2017; Shirley, 2018;Sousa et al, 2018;Ambretti et al, 2019). Consistently with these observations, our results show that ceftazidime-avibactam is effective against KPC and OXA-48 but not against CRKP strains harboring the VIM gene (Shirley, 2018;Garcıá-Castillo et al, 2018).…”

supporting

confidence: 87%

Biofilm Production by Carbapenem-Resistant Klebsiella pneumoniae Significantly Increases the Risk of Death in Oncological Patients

Domenico

Cavallo

Sivori

et al. 2020

Front. Cell. Infect. Microbiol.

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Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a prominent cause of nosocomial infections associated with high rates of morbidity and mortality, particularly in oncological patients. The hypermucoviscous (HMV) phenotype and biofilm production are key factors for CRKP colonization and persistence in the host. This study aims at exploring the impact of CRKP virulence factors on morbidity and mortality in oncological patients. A total of 86 CRKP were collected between January 2015 and December 2019. Carbapenem resistance-associated genes, antibiotic susceptibility, the HMV phenotype, and biofilm production were evaluated. The median age of the patients was 71 years (range 40–96 years). Clinically infected patients were 53 (61.6%), while CRKP colonized individuals were 33 (38.4%). The most common infectious manifestations were sepsis (43.4%) and pneumonia (18.9%), while rectal surveillance swabs were the most common site of CRKP isolation (81.8%) in colonized patients. The leading mechanism of carbapenem resistance was sustained by the KPC gene (96.5%), followed by OXA-48 (2.3%) and VIM (1.2%). Phenotypic CRKP characterization indicated that 55.8% of the isolates were strong biofilm-producers equally distributed between infected (54.2%) and colonized (45.8%) patients. The HMV phenotype was found in 22.1% of the isolates, which showed a significant (P<0.0001) decrease in biofilm production as compared to non-HMV strains. The overall mortality rate calculated on the group of infected patients was 35.8%. In univariate analysis, pneumoniae significantly correlated with death (OR 5.09; CI 95% 1.08–24.02; P=0.04). The non-HMV phenotype (OR 4.67; CI 95% 1.13–19.24; P=0.03) and strong biofilm-producing strains (OR 5.04; CI95% 1.39–18.25; P=0.01) were also associated with increased CRKP infection-related mortality. Notably, the multivariate analysis showed that infection with strong biofilm-producing CRKP was an independent predictor of mortality (OR 6.30; CI 95% 1.392–18.248; P=0.004). CRKP infection presents a high risk of death among oncological patients, particularly when pneumoniae and sepsis are present. In infected patients, the presence of strong biofilm-producing CRKP significantly increases the risk of death. Thus, the assessment of biofilm production may provide a key element in supporting the clinical management of high-risk oncological patients with CRKP infection.

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supporting

confidence: 87%

Biofilm Production by Carbapenem-Resistant Klebsiella pneumoniae Significantly Increases the Risk of Death in Oncological Patients

Domenico

Cavallo

Sivori

et al. 2020

Front. Cell. Infect. Microbiol.

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“…This finding was not statistically significant and it is unclear whether it is specific to OXA-48-producing K. pneumoniae isolates, as there were no controls used in the study (11). Inconsistencies with regard to in vitro susceptibility have been observed with the glycylcycline antibiotic tigecycline, with a broad range of percentages for susceptible isolates identified across different studies (35)(36)(37)(38). Table 1 lists MICs for a variety of these drugs.…”

mentioning

confidence: 99%

Treatment of Infections by OXA-48-Producing Enterobacteriaceae

Stewart

Harris

Henderson

et al. 2018

Antimicrob Agents Chemother

118

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Carbapenemase-producing (CPE) contribute significantly to the global public health threat of antimicrobial resistance. OXA-48 and its variants are unique carbapenemases with low-level hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. is typically located on a plasmid but may also be integrated chromosomally, and this gene has progressively disseminated throughout Europe and the Middle East. Despite the inability of OXA-48-like carbapenemases to hydrolyze expanded-spectrum cephalosporins, pooled isolates demonstrate high variable resistance to ceftazidime and cefepime, likely representing high rates of extended-spectrum beta-lactamase (ESBL) coproduction. data from pooled studies suggest that avibactam is the most potent beta-lactamase inhibitor when combined with ceftazidime, cefepime, aztreonam, meropenem, or imipenem. Resistance to novel avibactam combinations such as imipenem-avibactam or aztreonam-avibactam has not yet been reported in OXA-48 producers, although only a few clinical isolates have been tested. Although combination therapy is thought to improve the chances of clinical cure and survival in CPE infection, successful outcomes were seen in ∼70% of patients with infections caused by OXA-48-producing treated with ceftazidime-avibactam monotherapy. A carbapenem in combination with either amikacin or colistin has achieved treatment success in a few case reports. Uncertainty remains regarding the best treatment options and strategies for managing these infections. Newly available antibiotics such as ceftazidime-avibactam show promise; however, recent reports of resistance are concerning. Newer choices of antimicrobial agents will likely be required to combat this problem.

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“…A multicenter study of Enterobacterales carbapenemase-producing gram-negative bacteria (CPGNB), isolated from urine specimens, found a prevalence of 1.6%. OXA-48 was the most prevalent, followed by KPC and MBL ( 5 ).…”

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confidence: 99%

Carbapenemase-Producing Gram-Negative Bacteria in Andalusia, Spain, 2014–2018

López-Hernández¹,

Delgado-Valverde²,

Fernández-Cuenca³

et al. 2020

Emerg. Infect. Dis.

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The emergence and spread of carbapenemase-producing gram-negative bacteria is a major public health concern. We used data collected from microbiology laboratories as part of the PIRASOA program during 2014–2018 to study the epidemiology of carbapenemase-producing bacteria in Andalusia, Spain. Our findings highlight the importance of ongoing surveillance and epidemiologic studies for these bacteria.

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Activity of ceftazidime-avibactam against carbapenemase-producing Enterobacteriaceae from urine specimens obtained during the infection-carbapenem resistance evaluation surveillance trial (iCREST) in Spain

Cited by 30 publications

References 18 publications

Biofilm Production by Carbapenem-Resistant Klebsiella pneumoniae Significantly Increases the Risk of Death in Oncological Patients

Biofilm Production by Carbapenem-Resistant Klebsiella pneumoniae Significantly Increases the Risk of Death in Oncological Patients

Treatment of Infections by OXA-48-Producing Enterobacteriaceae

Carbapenemase-Producing Gram-Negative Bacteria in Andalusia, Spain, 2014–2018

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