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16 pages, 1050 KiB

Open AccessArticle

Bloodstream Infections Caused by Carbapenem-Resistant Pathogens in Intensive Care Units: Risk Factors Analysis and Proposal of a Prognostic Score

by Giorgia Montrucchio, Andrea Costamagna, Tommaso Pierani, Alessandra Petitti, Gabriele Sales, Emanuele Pivetta, Silvia Corcione, Antonio Curtoni, Rossana Cavallo, Francesco Giuseppe De Rosa and Luca Brazzi

Pathogens 2022, 11(7), 718; https://doi.org/10.3390/pathogens11070718 - 23 Jun 2022

Cited by 13 | Viewed by 2136

Abstract

Considering the growing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) bloodstream infection (BSI) in intensive care units (ICUs), the identification of specific risk factors and the development of a predictive model allowing for the early identification of patients at risk for CR-Klebsiella pneumoniae [...] Read more.

Considering the growing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) bloodstream infection (BSI) in intensive care units (ICUs), the identification of specific risk factors and the development of a predictive model allowing for the early identification of patients at risk for CR-Klebsiella pneumoniae, Acinetobacter baumannii or Pseudomonas aeruginosa are essential. In this retrospective case–control study including all consecutive patients showing an episode of BSI in the ICUs of a university hospital in Italy in the period January–December 2016, patients with blood culture positive for CR-GNB pathogens and for any other bacteria were compared. A total of 106 patients and 158 episodes of BSI were identified. CR-GNBs induced BSI in 49 patients (46%) and 58 episodes (37%). Prognosis score and disease severity at admission, parenteral nutrition, cardiovascular surgery prior to admission to ICU, the presence of sepsis and septic shock, ventilation-associated pneumonia and colonization of the urinary or intestinal tract were statistically significant in the univariate analysis. The duration of ventilation and mortality at 28 days were significantly higher among CR-GNB cases. The prognostic model based on age, presence of sepsis, previous cardiovascular surgery, SAPS II, rectal colonization and invasive respiratory infection from the same pathogen showed a C-index of 89.6%. The identified risk factors are in line with the international literature. The proposal prognostic model seems easy to use and shows excellent performance but requires further studies to be validated. Full article

(This article belongs to the Special Issue Resistant Mechanisms and Novel Antibiotics of Carbapenem-Resistant Crisis)

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19 pages, 1430 KiB

Open AccessArticle

A Variant Carbapenem Inactivation Method (CIM) for Acinetobacter baumannii Group with Shortened Time-to-Result: rCIM-A

by Dieter Mitteregger, Julian Wessely, Ivan Barišić, Branka Bedenić, Dieter Kosak and Michael Kundi

Pathogens 2022, 11(4), 482; https://doi.org/10.3390/pathogens11040482 - 18 Apr 2022

Cited by 6 | Viewed by 4201

Abstract

Carbapenem-resistant Acinetobacter baumannii group organisms (CRAB) are challenging because the choice between targeted, new antibiotic drug options and hygiene measures should be guided by a timely identification of resistance mechanisms. In CRAB, acquired class-D carbapenemases (CHDLs) are active against meropenem and imipenem. If [...] Read more.

Carbapenem-resistant Acinetobacter baumannii group organisms (CRAB) are challenging because the choice between targeted, new antibiotic drug options and hygiene measures should be guided by a timely identification of resistance mechanisms. In CRAB, acquired class-D carbapenemases (CHDLs) are active against meropenem and imipenem. If PCR methods are not the first choice, phenotypic methods have to be implemented. While promising, the carbapenemase inactivation method (CIM) using meropenem-hydrolysis is, however, hampered by poor performance or overly long time-to-result. We developed a rapid CIM (rCIM-A) with good performance using ertapenem, imipenem, and meropenem disks, 2-h permeabilization and incubation with the test strain in trypticase soy broth, and a read-out of residual carbapenem activity after 6 h, and optionally after 16–18 h. Using clinical isolates and type-strains of Acinetobacter (n = 67) not harboring carbapenemases (n = 28) or harboring acquired carbapenemases (n = 39), the sensitivity of detection was 97.4% with the imipenem disk after 6 h at a specificity of 92.9%. If the inhibition zone around the ertapenem disk at 6 h was 6 or ≤26 mm at 16–18 h, or ≤25.5 mm for meropenem, the specificity was 100%. Because of the high negative predictive value, the rCIM-A seems particularly appropriate in areas of lower CRAB-frequency. Full article

(This article belongs to the Special Issue Resistant Mechanisms and Novel Antibiotics of Carbapenem-Resistant Crisis)

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14 pages, 957 KiB

Open AccessArticle

Molecular Epidemiology, Risk Factors and Clinical Outcomes of Carbapenem-Nonsusceptible Enterobacter cloacae Complex Infections in a Taiwan University Hospital

by Chao-Ju Chen, Po-Liang Lu, Shu-Huei Jian, Hsiao-Ling Fu, Po-Hao Huang and Chung-Yu Chang

Pathogens 2022, 11(2), 151; https://doi.org/10.3390/pathogens11020151 - 25 Jan 2022

Cited by 6 | Viewed by 2683

Abstract

The genus Enterobacter is a member of the ESKAPE group, which contains the major resistant bacterial pathogens. Enterobacter cloacae complex (ECC) has emerged as a clinically significant cause of a wide variety of nosocomial infections. Carbapenem-nonsusceptible Enterobacter cloacae complex (CnsECC) has become an [...] Read more.

The genus Enterobacter is a member of the ESKAPE group, which contains the major resistant bacterial pathogens. Enterobacter cloacae complex (ECC) has emerged as a clinically significant cause of a wide variety of nosocomial infections. Carbapenem-nonsusceptible Enterobacter cloacae complex (CnsECC) has become an emerging threat to public health but there is still a lack of comprehensive molecular and clinical epidemiological analysis. A total of 157 CnsECC isolates were recovered during October 2011 to August 2017. hsp60 gene sequencing and pulsed-field gel electrophoresis (PFGE) were applied to discriminate the species, genetic clusters and clonal relatedness. All the isolates were subjected to polymerase chain reaction (PCR) analysis for carbapenemase, AmpC-type β-lactamase, and extended spectrum β-lactamase (ESBL) genes. Clinical data were collected on all patients for comparing clinical risks and outcomes between patients with carbapenemase-producing (CP)-CnsECC compared with non-CP-CnsECC infection. The most commonly identified species was E. hormaechei subsp. hoffmannii (47.1%), followed by E. hormaechei subsp. steigerwaltii (24.8%). Different species of CnsECC isolates showed heterogeneity in resistance patterns to piperacillin/tazobactam, cefepime and levofloxacin. In the present study, we observed that E. hormaechei subsp. hoffmannii was characterized with higher cefepime and levofloxacin resistance rate but lower piperacillin/tazobactam resistance rate relative to other species of CnsECC. CP-CnsECC comprised 41.1% (65 isolates) and all of these isolates carried IMP-8. In this study, 98% of patients had antimicrobial therapy prior to culture, with a total of 57/150 (38%) patients being exposed to carbapenems. Chronic pulmonary disease (OR: 2.51, 95% CI: 1.25–5.06), received ventilator support (OR: 5.54, 95% CI: 2.25–12.03), steroid exposure (OR: 3.88, 95% CI: 1.91–7.88) and carbapenems exposure (OR: 2.17, 95% CI: 1.10–4.25) were considered risk factors associated with CP-CnsECC infection. The results suggest that CP-CnsECC are associated with poorer outcomes including in-hospital mortality, 30-day mortality and 100-day mortality. Our study provides insights into the epidemic potential of IMP-8-producing E. cloacae for healthcare-associated infections and underscores the importance of understanding underlying resistance mechanisms of CnsECC to direct antibiotic treatment decisions. Full article

(This article belongs to the Special Issue Resistant Mechanisms and Novel Antibiotics of Carbapenem-Resistant Crisis)

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11 pages, 2848 KiB

Open AccessArticle

Predominance of Acinetobacter spp., Harboring the bla_IMP Gene, Contaminating the Hospital Environment in a Tertiary Hospital in Mwanza, Tanzania: A Cross-Sectional Laboratory-Based Study

by Vitus Silago, Eveline C. Mruma, Betrand Msemwa, Conjester I. Mtemisika, Shukurani Phillip, Reuben A. Ndagula, Maria M. Said, Martha F. Mushi and Stephen E. Mshana

Pathogens 2022, 11(1), 63; https://doi.org/10.3390/pathogens11010063 - 04 Jan 2022

Cited by 3 | Viewed by 1794

Abstract

Data on colonization and hospital contamination of carbapenem-resistant Gram-negative bacteria (CR-GNB) are limited in low- and middle-income countries. We designed this study to determine the prevalence and co-existence of carbapenemase genes among CR-GNB isolated from clinical, colonization, and hospital environmental samples at a [...] Read more.

Data on colonization and hospital contamination of carbapenem-resistant Gram-negative bacteria (CR-GNB) are limited in low- and middle-income countries. We designed this study to determine the prevalence and co-existence of carbapenemase genes among CR-GNB isolated from clinical, colonization, and hospital environmental samples at a tertiary hospital in Mwanza, Tanzania. The modified Hodge test (MHT), the combined disk test (CDT), and the double-disk synergy test (DDST) were used for the phenotypic detection of carbapenemases. A multiplex PCR assay was used to detect bla_IMP and bla_KPC, and a singleplex PCR assay was used to detect bla_OXA-48. Data were analyzed by STATA version 13.0. Overall, 68.8% (44/64) of the CR-GNB had at least one phenotype by phenotypic methods, whereby 60.9% (39/64) were both CDT and DDST positive and 31.3% (20/64) were MHT positive. A total of 23/64 (35.9%) had at least one of the genes tested with the predominance of bla_IMP (91.3%; 21/23). In addition, 47.7% (21/44) of the CR-GNB phenotypes had at least one gene. Around 47.8% (11/23) of the CR-GNB carried multiple genes encoding for carbapenem resistance, with the maximum co-existence of bla_IMP/bla_KPC/bla_OXA-48 (45.5%; 5/11). The majority of carbapenem-resistant genes were detected in Acinetobacter spp. (82.6%; 19/23) and isolated from bed swabs (69.6%; 16/23). Acinetobacter spp. carrying the bla_IMP gene predominantly contaminated the hospital environment. Therefore, we recommend routine decontamination of inanimate hospital surfaces, including patient beds. Full article

(This article belongs to the Special Issue Resistant Mechanisms and Novel Antibiotics of Carbapenem-Resistant Crisis)

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10 pages, 793 KiB

Open AccessArticle

Synergistic Combination of AS101 and Azidothymidine against Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae

by Chung-Lin Sung, Wei-Chun Hung, Po-Liang Lu, Lin Lin, Liang-Chun Wang, Tsung-Ying Yang and Sung-Pin Tseng

Pathogens 2021, 10(12), 1552; https://doi.org/10.3390/pathogens10121552 - 29 Nov 2021

Cited by 2 | Viewed by 1844

Abstract

Owing to the over usage of carbapenems, carbapenem resistance has become a vital threat worldwide, and, thus, the World Health Organization announced the carbapenem-resistant Enterobacteriaceae (CRE) as the critical priority for antibiotic development in 2017. In the current situation, combination therapy would be [...] Read more.

Owing to the over usage of carbapenems, carbapenem resistance has become a vital threat worldwide, and, thus, the World Health Organization announced the carbapenem-resistant Enterobacteriaceae (CRE) as the critical priority for antibiotic development in 2017. In the current situation, combination therapy would be one solution against CRE. Azidothymidine (AZT), a thymidine analog, has demonstrated its synergistically antibacterial activities with other antibiotics. The unexpected antimicrobial activity of the immunomodulator ammonium trichloro(dioxoethylene-o,o’)tellurate (AS101) has been reported against carbapenem-resistant Klebsiella pneumoniae (CRKP). Here, we sought to investigate the synergistic activity between AS101 and AZT against 12 CRKP clinical isolates. According to the gene detection results, the bla_OXA-1 (7/12, 58.3%)_, bla_DHA (7/12, 58.3%), and bla_KPC (7/12, 58.3%) genes were the most prevalent ESBL, AmpC, and carbapenemase genes, respectively. The checkerboard analysis demonstrated the remarkable synergism between AS101 and AZT, with the observable decrease in the MIC value for two agents and the fractional inhibitory concentration (FIC) index ≤0.5 in all strains. Hence, the combination of AS101 and azidothymidine could be a potential treatment option against CRKP for drug development. Full article

(This article belongs to the Special Issue Resistant Mechanisms and Novel Antibiotics of Carbapenem-Resistant Crisis)

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11 pages, 249 KiB

Open AccessArticle

In-Vitro Efficacy of Cefiderocol in Carbapenem-Non-Susceptible Gram-Negative Bacilli of Different Genotypes in Sub-Region of North Rhine Westphalia, Germany

by Beniam Ghebremedhin and Parviz Ahmad-Nejad

Pathogens 2021, 10(10), 1258; https://doi.org/10.3390/pathogens10101258 - 29 Sep 2021

Cited by 6 | Viewed by 1780

Abstract

In the last two decades, the worldwide dissemination of multidrug-resistant Gram-negative bacteria (MDR-GNB) has continued. Therapy options for such infections caused by MDR-GNB remain scarce, and only few new antimicrobial agents have been granted market approval. Cefiderocol has been approved for the treatment [...] Read more.

In the last two decades, the worldwide dissemination of multidrug-resistant Gram-negative bacteria (MDR-GNB) has continued. Therapy options for such infections caused by MDR-GNB remain scarce, and only few new antimicrobial agents have been granted market approval. Cefiderocol has been approved for the treatment of infections associated with aerobic GNB with limited therapy options. This study evaluated the in vitro efficacy of cefiderocol against carbapenem-non-susceptible clinical GNB isolates from Germany. A total of 115 non-duplicate carbapenem-nonsusceptible GNB isolates, 61 (53.05%) of which were Enterobacterales species and 54 (46.95%) were non-fermenters (Acinetobacter baumanii and Pseudomonas aeruginosa), were investigated for their cefiderocol susceptibility. Minimum inhibitory concentrations (MICs) for cefiderocol were determined by disk diffusion, according to EUCAST (European committee for antimicrobial susceptibility testing). Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/-dynamic breakpoints were used. The most common pathogen was A. baumannii (33.91%), followed by Klebsiella pneumoniae (31.3%), P. aeruginosa (13.04%) and Escherichia coli (9.57%). Overall, 83.6% (51/61) of the Enterobacterales and 81.48% (44/54) of the non-fermenters were susceptible towards cefiderocol. In total, 20 species of Enterobacterales and non-fermenting GNB were resistant towards cefiderocol, irrespective of the isolation year (2014 to 2021). Moreover, the majority of the resistant isolates were among the OXA-23 producing A. baumannii (n = 7/26; 26.92%) from patients hospitalized during 2018 and 2019. Cefiderocol demonstrated high in vitro susceptibility rates against a wide range of carbapenem-non-susceptible GNB, including carbapenemase-producing isolates. Cefiderocol exhibited stability against hydrolysis by all carbapenemases, including metallo-β-lactamases (MBLs), except that few OXA-producing isolates exhibited resistance towards cefiderocol. Full article

(This article belongs to the Special Issue Resistant Mechanisms and Novel Antibiotics of Carbapenem-Resistant Crisis)

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3 pages, 181 KiB

Open AccessReply

Reply to Muntean et al. Comment on “Mitteregger et al. A Variant Carbapenem Inactivation Method (CIM) for Acinetobacter baumannii Group with Shortened Time-to-Result: rCIM-A. Pathogens 2022, 11, 482”

by Dieter Mitteregger, Julian Wessely, Ivan Barišić, Branka Bedenić, Dieter Kosak and Michael Kundi

Pathogens 2022, 11(7), 767; https://doi.org/10.3390/pathogens11070767 - 05 Jul 2022

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Abstract

We appreciate the interest in our publication and agree that a different acronym for the method would have been better [...] Full article

(This article belongs to the Special Issue Resistant Mechanisms and Novel Antibiotics of Carbapenem-Resistant Crisis)

3 pages, 208 KiB

Open AccessComment

Comment on Mitteregger et al. A Variant Carbapenem Inactivation Method (CIM) for Acinetobacter baumannii Group with Shortened Time-to-Result: rCIM-A. Pathogens 2022, 11, 482

by Andrei-Alexandru Muntean, Madalina-Maria Muntean, Saoussen Oueslati, Remy Bonnin, Thierry Naas and Mircea Ioan Popa

Pathogens 2022, 11(7), 751; https://doi.org/10.3390/pathogens11070751 - 01 Jul 2022

Cited by 1 | Viewed by 904

Abstract

We have read the article published by Mitteregger et al. [...] Full article

(This article belongs to the Special Issue Resistant Mechanisms and Novel Antibiotics of Carbapenem-Resistant Crisis)

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