Mortality-related factors in patients with OXA-48 carbapenemase-producing Klebsiella pneumoniae bacteremia

Rodriguez, O.; Sousa, Adrián; Pérez-Rodríguez, María Teresa; Martínez-Lamas, Lucía; Suárez, Rebeca Longueira; Martinez, Chiara; Pino, Caleb; Vidal, Francesc; Pérez-Landeiro, Antonio; Casal, Manuel Crespo

doi:10.1097/md.0000000000024880

Cited by 11 publications

(8 citation statements)

References 38 publications

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“…1 CRE is associated with higher mortality rate, with an approximately 2-fold increase in mortality compared with infections with carbapenem-susceptible Enterobacterales. 2 Carbapenemases produced by CRE have been classified into three different groups according to Ambler classification: class A [e.g. Klebsiella pneumoniae carbapenemase (KPC)], class B or MBL (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy

AlQahtani

Alghamdi

Alobaidallah

et al. 2022

JAC-Antimicrobial Resistance

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Background Carbapenem-resistant Enterobacterales (CRE) is an urgent public health threat of significant global concern. Few observational studies have evaluated the clinical outcomes for treatment of CRE harbouring OXA-48 or NDM genes with ceftazidime/avibactam. Previous findings showed lower 30 day mortality with ceftazidime/avibactam ranges between 8.3% and 22%. Method This single-centre retrospective cohort study included adult patients aged ≥18 years admitted to King Abdulaziz Medical City (KAMC) who had received ceftazidime/avibactam for at least 72 h for infections caused by CRE with genes encoding for carbapenemase production (CP-CRE). Results A total of 211 patients, mostly male (57%), having CP-CRE infections treated with ceftazidime/avibactam were included, with an average age of 62 years. More than 50% of patients were critically ill, for which 46% received invasive ventilation and 36% were on inotropes. The most frequent infectious disease was hospital/ventilator-acquired pneumonia with Klebsiella pneumoniae being the most frequent causative pathogen. The majority of isolates harboured OXA-48 (81%), followed by NDM ± OXA-48 (19%). The overall clinical cure and 30 day mortality was 78% and 21% respectively (stratified per gene: 79% and 21.6% for OXA-48 and 75% and 17.5% for NDM ± OXA-48). Conclusions This was the largest study that evaluated clinical outcomes associate with CP-CRE harbouring OXA-48 gene infections treated with ceftazidime/avibactam. Clinical cure and 30 day mortality were consistent with those of previous studies. Findings suggested that combination therapy with ceftazidime/avibactam had no direct impact on clinical outcomes for CP-CRE with OXA-48.

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Section: Introductionmentioning

confidence: 99%

“…oxacillinase (OXA-48)]. 2 , 3 Local data that describe the molecular epidemiology of CRE in Saudi Arabia found that OXA-48 accounted for 71.2% ( n = 292) of 410 carbapenemase-producing CRE isolates, followed by NDM ( n = 85; 20.7%) and NDM + OXA-48 ( n = 33; 8%). 4 …”

Section: Introductionmentioning

confidence: 99%

Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy

AlQahtani

Alghamdi

Alobaidallah

et al. 2022

JAC-Antimicrobial Resistance

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“…Surprisingly, after analysing the use of antibiotics before a positive blood culture was observed, we found that when there was no significant difference in the TBSA and the third-degree burn are between the two groups of patients, whether the antibiotics that were used were appropriate had no effect on the length of hospital stay, the length of ICU stay, or in-hospital mortality. However, it has previously been reported that whether or not the initial antibiotic used for in patients with infection is appropriate is not associated with mortality 36,37 and that the use of inappropriate initial antibiotics in infected patients leads to an increase in mortality 25,38 www.nature.com/scientificreports/ Such contradictory results may be explained as follows: 1. In addition to the selection of appropriate antibiotics, whether anti-infective treatment is effective is also related to the specific bacterial resistance and the method of antibiotic administration 25 .…”

Section: Discussionmentioning

confidence: 99%

Characteristics of bloodstream infection and initial antibiotic use in critically ill burn patients and their impact on patient prognosis

Yin

Bei-wen

Zhenzhu

et al. 2022

Sci Rep

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To investigate the bacterial epidemiology of blood cultures taken during the treatment of critically ill burn patients, the use of antibiotics at admission and before the observation of positive blood cultures, and their effect on prognosis. A retrospective study method was used. From January 1, 2010, to December 31, 2019, burn patients who met the inclusion criteria and were treated at the Burn Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, were enrolled in the study. Data were collected from the patients’ electronic medical records. General patient information, including length of hospital stay, length of intensive care unit (ICU) stay, in-hospital mortality, the bacteria epidemiological characteristics of blood cultures, and the use of antibiotics within 24 h after admission and before a positive blood culture was observed, was collected. Independent sample t tests and χ2 tests were used to compare the effects of a positive blood culture and the use of appropriate antibiotics within 24 h after admission and before the observation of a positive blood culture on prognosis. (1) The three most frequently detected bacteria in the blood cultures were Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, and the amount of K. pneumoniae detected increased gradually. (2) Compared with the group of patients who were negative for bloodstream infection , the positive bloodstream infection group had a larger total body burn surface area (TBSA) (t = − 5.097, P = 0.000) and third-degree burn area (t = − 5.133, P = 0.000), a significantly longer length of hospital stay (t = 3.003, P = 0.003) and the length of ICU stay (t = 4.258, P = 0.000), and a significantly higher rate of in-hospital mortality (χ2 = 8.485, P = 0.004). When K. pneumoniae was detected, the length of hospital stay (t = 2.148, P = 0.035) and the length of ICU stay (t = 2.880, P = 0.005) were significantly prolonged. (3) The two antibiotics that were most frequently used in patients with acute burns within 24 h after admission were lincomycin (90 cases, 29.32%) and carbapenems (79 cases, 25.73%). Comparing the clinical characteristics of the lincomycin group and the carbapenem group, the TBSA (t = − 3.34, P = 0.001) and the third-degree burn area (t = − 6.08, P = 0.000) of the patients in the carbapenem group were larger, and the length of hospital stay (t = − 2.136, P = 0.035) and length of ICU stay (t = − 5.18, P = 0.000) were longer, but the difference in in-hospital mortality was not statistically significant (χ2 = 1.983, P = 0.159). (4) Comparing the group with appropriate initial antibiotic use within 24 h of admission to the inappropriate use group, the TBSA (t = − 0.605, P = 0.547), the third-degree burn area (t = 0.348, P = 0.729), the length of hospital stay (t = − 0.767, P = 0.445), the length of ICU stay (t = − 0.220, P = 0.827) and in-hospital mortality (χ2 = 1.271, P = 0.260) were not significantly different. (5) Comparing the group with appropriate antibiotic use before a positive blood culture was observed to the group with inappropriate antibiotic use, the TBSA (t = − 0.418, P = 0.677), the third-degree burn area (t = 0.266, P = 0.791), the length of hospital stay, the length of ICU stay (t = 0.995, P = 0.322) and in-hospital mortality (χ2 = 1.274, P = 0.259) were not significantly different. We found that patients with a positive blood culture had a larger burn area and a worse prognosis; that the greater the amount of K. pneumoniae in the bloodstream of burn patients was, the longer the hospital and ICU stays were; that whether appropriate antibiotics were administered to acute critical burn patients 24 h after admission had no effect on the prognosis; and that whether appropriate antibiotics were administered before a positive blood culture was observed had no effect on prognosis.

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“…Nosocomial outbreaks of OXA-48 producing K. pneumoniae have been associated with fatal outcomes. Invasive infections, notably bacteremia, caused by K. pneumoniae isolates carrying bla OXA-48 , are associated with high-mortality (Navarro-San Francisco et al ., 2013; Madueño et al ., 2018; Pantel et al ., 2016; Taoufik et al ., 2019; Rodríguez et al ., 2021). Further, carbapenem therapy in patients infected with bla OXA-48 has been linked with a high risk of treatment failure (Balkan et al ., 2014; Shaidullina et al ., 2020).…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic analyses of plasmid resistome changes in pOXA-48

Fordham

Mantzouratou

Sheridan

2022

Preprint

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Infections caused by carbapenem resistant Enterobacteriales (CPE) represent a significant threat in clinical settings. blaOXA-48 is one of the most frequent carbapenemase genes among Enterobacteriales. The blaOXA-48 is typically encoded on the prototypical IncL conjugative pOXA-48 plasmid. The pOXA-48 plasmid encodes only the blaOXA-48 resistance gene. However, aminoglycoside and extended spectrum β-lactamase (ESBL) resistance genes have also been detected on the same pOXA-48 plasmid backbone. These pOXA-48 plasmids encoding additional antimicrobial resistance (AMR) genes have been associated with both poor patient outcome and increased minimal inhibitory concentrations (MICs) to antibiotics including broad-spectrum cephalosporins. The blaOXA-48 gene was sourced from the pOXA-48 reference plasmid and set as a query using the BLASTn tool. Non-duplicate blaOXA-48 containing plasmids were downloaded, incompatibility typed and annotated for resistance genes using ResFinder 4.0. Bioinformatic analyses identified three distinct variants of the pOXA-48 plasmid encoding 4, 5, and 6 antimicrobial resistance genes. All plasmids encoded the ESBL blaCTX-M-14b, blaOXA-48 and either 2, 3 or 4 aminoglycoside resistance genes, in addition to conjugative transfer machinery. Plasmid variants 1 and 3 encoded aminoglycoside genes bracketed between IS26 and ISEc63 insertion elements, forming a potential transposon. The potential transposon structure had resemblance to the Tn5393 transposon (accession: M96392), including both aph(3'')-Ib, aph(6)-Id genes, and a Tn3 resolvase. The IS element ISEcp1 lies upstream of blaCTX-M-14b. All three plasmid variants appear related. Notably, all pOXA-48 plasmid variants were identified in multiple countries. In particular, variant 1 including 6 AMR genes was detected in 7 unique countries. Plasmids encoding additional AMR genes were associated with clinical/surveillance samples suggesting antibiotic pressure in clinical settings may promote changes in the resistome of pOXA-48. Acquisition of pOXA-48 resistant plasmids carrying additional AMR genes beyond blaOXA-48 can change the resistome of susceptible isolates in a single-step, rendering previously susceptible strains refractory to almost all available treatment options.

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Mortality-related factors in patients with OXA-48 carbapenemase-producing Klebsiella pneumoniae bacteremia

Cited by 11 publications

References 38 publications

Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy

Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy

Characteristics of bloodstream infection and initial antibiotic use in critically ill burn patients and their impact on patient prognosis

Bioinformatic analyses of plasmid resistome changes in pOXA-48

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