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JAC-antimicrobial Resistance Jun 2024To investigate the activities of ceftolozane/tazobactam and imipenem/relebactam against , and isolated from hospitalized patients in Mexico in 2017-2021.
OBJECTIVES
To investigate the activities of ceftolozane/tazobactam and imipenem/relebactam against , and isolated from hospitalized patients in Mexico in 2017-2021.
METHODS
MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 breakpoints. β-Lactamase genes were identified in ceftolozane/tazobactam-, imipenem/relebactam-, and/or imipenem-non-susceptible isolates.
RESULTS
Ceftolozane/tazobactam and imipenem/relebactam inhibited 89% and 99% of isolates (= 2337), and 87% and 94% of isolates (= 1127). Sixty-four percent of and 47% of had an ESBL non-carbapenem-resistant Enterobacterales (ESBL non-CRE) phenotype. Eighty-six percent and 91% of ESBL non-CRE and were ceftolozane/tazobactam susceptible, and 99.9% and 99.8% were imipenem/relebactam susceptible. Ceftolozane/tazobactam was the most active agent studied against (= 1068; 83% susceptible), 9-28 percentage points higher than carbapenems and comparator β-lactams excluding imipenem/relebactam (78% susceptible). Ceftolozane/tazobactam remained active against 35%-58%, and imipenem/relebactam against 32%-42%, of in meropenem-, piperacillin/tazobactam-, and cefepime-non-susceptible subsets. The majority of isolates of ceftolozane/tazobactam-non-susceptible carried an ESBL, whereas among ceftolozane/tazobactam-non-susceptible and , the majority carried carbapenemases. The most prevalent carbapenemase observed among (estimated at 0.7% of all isolates), (4.8%) and (10.0%) was an MBL. Almost all imipenem/relebactam-non-susceptible and carried MBL or OXA-48-like carbapenemases, whereas among imipenem/relebactam-non-susceptible , 56% carried MBL or GES carbapenemases.
CONCLUSIONS
Ceftolozane/tazobactam and imipenem/relebactam may provide treatment options for patients infected with β-lactam-non-susceptible Gram-negative bacilli, excluding isolates carrying an MBL- or OXA-48-like carbapenemase.
PubMed: 38799180
DOI: 10.1093/jacamr/dlae077 -
Open Forum Infectious Diseases May 2024Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in...
BACKGROUND
Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established.
METHODS
An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed.
RESULTS
Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: -0.89 days (95% confidence interval [CI], -1.38 to -.41); linezolid: -0.89 days (95% CI, -1.27 to -.52); meropenem: -0.97 days (95% CI, -1.39 to -.56); tigecycline: -1.41 days (95% CI, -2.19 to -.63); < .001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (-43.49; 95% CI, -58.61 to -28.37; < .001), tigecycline (-35.47; 95% CI, -44.94 to -26.00; < .001), and daptomycin (-9.47; 95% CI, -15.25 to -3.68; = .002).
DISCUSSION
A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.
PubMed: 38798895
DOI: 10.1093/ofid/ofae235 -
Microorganisms May 2024Antibiotic resistance is a global health crisis. Notably, carbapenem-resistant Enterobacterales (CRE) pose a significant clinical challenge due to the limited effective...
Antibiotic resistance is a global health crisis. Notably, carbapenem-resistant Enterobacterales (CRE) pose a significant clinical challenge due to the limited effective treatment options. This problem is exacerbated by persisters that develop upon antibiotic exposure. Bacteria persisters can tolerate high antibiotic doses and can cause recalcitrant infections, potentially developing further antibiotic resistance. Iron is a critical micronutrient for survival. We aimed to evaluate the utility of iron chelators, alone and in combination with antibiotics, in managing persisters. We hypothesized that iron chelators eradicate CRE persisters in vitro, when administered in combination with antibiotics. Our screening revealed three clinical isolates with bacteria persisters that resuscitated upon antibiotic removal. These isolates were treated with both meropenem and an iron chelator (deferoxamine mesylate, deferiprone or dexrazoxane) over 24 h. Against our hypothesis, bacteria persisters survived and resuscitated upon withdrawing both the antibiotic and iron chelator. Pursuing our aim, we next hypothesized that iron chelation is feasible as a post-antibiotic treatment in managing and suppressing persisters' resuscitation. We exposed bacteria persisters to an iron chelator without antibiotics. Flow cytometric assessments revealed that iron chelators are inconsistent in suppressing persister resuscitation. Collectively, these results suggest that the iron chelation strategy may not be useful as an antibiotic adjunct to target planktonic bacteria persisters.
PubMed: 38792801
DOI: 10.3390/microorganisms12050972 -
Journal of Global Antimicrobial... May 2024The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) presents significant health challenges. Here, we present the structural genome sequence of an...
OBJECTIVE
The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) presents significant health challenges. Here, we present the structural genome sequence of an NDM-5-producing K. pneumoniae (HZKP2) in China.
METHODS
Antimicrobial susceptibility tests were conducted via broth microdilution. Whole-genome sequencing (WGS) was performed for genomic analysis. Wzi and capsular polysaccharide (KL) were analysed using Kaptive. Resistance genes, virulence factors, and comparative genomics analyses were also conducted. Multilocus sequence typing (MLST), replicons type, and core genome multilocus sequence typing (cgMLST) analysis were further conducted using BacWGSTdb server.
RESULTS
HZKP2 was resistant to cefepime, ceftazidime, ciprofloxacin, ciprofloxacin, meropenem, and ertapenem. It harbored fosA, bla, oqxA, oqxB, sul1, dfrA1, tet(A), floR, aph(6)-Id, aph(3'')-Ib, sul2, bla, and bla. Based on the RAST results, 5563 genes that belonged to 398 subsystems were annotated. The complete genome sequence of HZKP2 was characterized as ST1, wzi 19, and KL19, with five contigs totaling 5,654,446 bp, including one chromosome and four plasmids. Further analysis found that bla was located in a 46,161 bp IncX3 plasmid (pHZKP2-3). The genetic structure of bla gene was ISKox3-IS26-ble-bla-IS5-ISAb125-IS3000. Further analysis revealed that insertion sequences mediated the dissemination of bla from other species of Enterobacterales. Phylogenetic analysis showed that the closest relative was from a human stool specimen in China, which differed by 53 cgMLST alleles.
CONCLUSION
Our study provides the first structural perspective of the ST1 K. pneumoniae isolate producing NDM-5 in China. These results could provide valuable insights into the genetic characteristics, antimicrobial resistance mechanisms, and transmission dynamics of CRKP in clinical settings.
PubMed: 38789084
DOI: 10.1016/j.jgar.2024.05.001 -
Journal of Global Antimicrobial... May 2024The treatment options available for infections caused by multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol (CFDC) is a novel siderophore...
In vitro activity of cefiderocol against carbapenemase-producing and meropenem-non-susceptible Gram-negative bacteria collected in the Japan Antimicrobial Resistant Bacterial Surveillance.
OBJECTIVES
The treatment options available for infections caused by multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol (CFDC) is a novel siderophore cephalosporin that exhibits activity against these pathogens. Several studies have reported the in vitro activity of CFDC against isolates from Europe, the United States, and China, but the activity against carbapenem-resistant bacteria with IMP-type carbapenemase has not been extensively studied. We, therefore, studied the in vitro activities of CFDC against carbapenem-resistant bacteria with available genomic backgrounds based on whole-genome sequencing (WGS) in Japan, where the IMP-type is the predominant carbapenemase produced by Gram-negative rods.
METHODS
We selected 603 isolates (528 Enterobacterales, 18 Pseudomonas aeruginosa, and 57 Acinetobacter spp.) from a collection of Gram-negative clinical isolates collected during a Japan Antimicrobial Resistance Bacterial Surveillance program and evaluated the antimicrobial activities of CFDC, ceftolozane/tazobactam (CTLZ/TAZ), imipenem-relebactam (IPM/REL), and ceftazidime/avibactam (CAZ/AVI) against carbapenemase-producing Enterobacterales, carbapenemase-non-producing meropenem-non-susceptible Enterobacterales, and carbapenemase-producing nonfermentative bacteria.
RESULTS
Among these, 97.7% of carbapenemase-producing Enterobacterales (99.2% of IMP-type carbapenemase-producing Enterobacterales), 100% of carbapenemase-producing P. aeruginosa, and 91.2% of carbapenemase-producing Acinetobacter spp. were susceptible to CFDC, showing better antimicrobial activity than the other antimicrobial agents evaluated in this study. CFDC was highly effective against class A-, B-, and D β-lactamase-harbouring isolates when compared to the other antimicrobial agents. In addition, the relationship between CFDC resistance and three genetic factors involved in resistance was discussed.
CONCLUSIONS
This is the first large-scale study to systematically demonstrate the efficacy of CFDC against IMP-type carbapenemase-producing strains with known genomic backgrounds.
PubMed: 38789082
DOI: 10.1016/j.jgar.2024.05.009 -
PloS One 2024Wastewater discharge into the environment in resource-poor countries poses a threat to public health. Studies in this area within these countries are limited, and the...
Wastewater discharge into the environment in resource-poor countries poses a threat to public health. Studies in this area within these countries are limited, and the use of high-throughput whole-genome sequencing technologies is lacking. Therefore, understanding of environmental impacts is inadequate. The present study investigated the antibiotic resistance profiles and diversity of beta-lactamases in Escherichia coli strains isolated from environmental water sources in Accra, Ghana. Microbiological analyses were conducted on wastewater samples from three hospitals, a sewage and wastewater treatment plant, and water samples from two urban surface water bodies. Confirmed isolates (N = 57) were selected for phenotypic antibiotic resistance profiles. Multi-drug-resistant isolates (n = 25) were genome sequenced using Illumina MiSeq sequencing technology and screened for sequence types, antibiotic resistance, virulence and beta-lactamase genes, and mobile genetic elements. Isolates were frequently resistant to ampicillin (63%), meropenem (47%), azithromycin (46%), and sulfamethoxazole-trimethoprim (42%). Twenty different sequence types (STs) were identified, including clinically relevant ones such as ST167 and ST21. Five isolates were assigned to novel STs: ST14531 (n = 2), ST14536, ST14537, and ST14538. The isolates belonged to phylogroups A (52%), B1 (44%), and B2 (4%) and carried β-lactamase (TEM-1B, TEM-1C, CTX-M-15, and blaDHA-1) and carbapenemase (OXA-1, OXA-181) resistance genes. Dominant plasmid replicons included Col440I (10.2%) and IncFIB (AP001918) (6.8%). Polluted urban environments in Accra are reservoirs for antibiotic-resistant bacteria, posing a substantial public health risk. The findings underscore the need for targeted public health interventions to mitigate the spread of antibiotic-resistant bacteria and protect public health.
Topics: Ghana; Escherichia coli; Drug Resistance, Multiple, Bacterial; beta-Lactamases; Humans; Wastewater; Public Health; Anti-Bacterial Agents; Water Microbiology; Microbial Sensitivity Tests; Genomics; Whole Genome Sequencing; Phylogeny; Sewage; Genome, Bacterial
PubMed: 38787855
DOI: 10.1371/journal.pone.0301531 -
Antibiotics (Basel, Switzerland) May 2024The spread of superbugs in dairy products can jeopardize global public health. To date, information on the incidence rates of virulent and β-lactams-resistant (BLR) in...
Rumi and Pasteurized Kareish Cheeses Are a Source of β-Lactam-Resistant in the Nile Delta Region of Egypt: Insights into Their Incidence, AMR Pattern, Genotypic Determinants of Virulence and β-Lactam Resistance.
The spread of superbugs in dairy products can jeopardize global public health. To date, information on the incidence rates of virulent and β-lactams-resistant (BLR) in cheeses from rural areas of Egypt has been lacking. Biochemical, serological, antibiotic susceptibility, and multiplex PCR (M-PCR) tests were performed to identify and characterize isolates. In this study, 44 (15.71%) isolates of eight different serotypes were recovered from 280 samples of Rumi and pasteurized Kariesh cheeses across the Nile Delta region of Egypt. The most predominant serotypes were . Typhimurium, . Enteritidis, and . Infantis. The virulence genes (, , and ) were identified in all isolates. However, was only detected in . Typhimurium. The highest resistance was developed against Erythromycin and Clindamycin (90.91%), followed by Ceftazidime and Cephalothin (84.09%). Meropenem and colistin were the most effective antibiotics. A high proportion (79.55%) of multi-drug resistance (MDR) isolates carried narrow spectrum (NS), extended-spectrum (ES), and AmpC-BLR genes. The , , , , and BLR genes were positive in 37.04%, 29.63%, 25.93%, 14.81%, 37.04%, and 3.70% of isolates, respectively. In conclusion, a high prevalence of virulence and BLR genes harboring strains in Egyptian cheeses is considered a great threat to public health.
PubMed: 38786185
DOI: 10.3390/antibiotics13050454 -
Antibiotics (Basel, Switzerland) May 2024Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment...
Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing and vancomycin-resistant in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.
PubMed: 38786160
DOI: 10.3390/antibiotics13050432 -
Antibiotics (Basel, Switzerland) May 2024This study aimed to characterize the impact of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of meropenem in neonates and children and to...
This study aimed to characterize the impact of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of meropenem in neonates and children and to provide recommendations for meropenem dosing in this specific population of patients. Therapeutic drug monitoring (152 meropenem plasma concentrations) data from 45 patients (38 received ECMO) with a body weight (BW) of 7.88 (3.62-11.97) kg (median (interquartile range)) and postnatal age of 3 (0-465) days were collected. The population PK analysis was performed using NONMEM V7.3.0. Monte Carlo simulations were performed to assess the probability of target achievement (PTA) for 40% of time the free drug remained above the minimum inhibitory concentration (fT > MIC) and 100% fT > MIC. BW was found to be a significant covariate for the volume of distribution (Vd) and clearance (CL). Additionally, continuous renal replacement therapy (CRRT) was associated with a two-fold increase in Vd. In the final model, the CL and Vd for a typical patient with a median BW of 7.88 kg that was off CRRT were 1.09 L/h (RSE = 8%) and 3.98 L (14%), respectively. ECMO did not affect meropenem PK, while superimposed CRRT significantly increased Vd. We concluded that current dosing regimens provide acceptably high PTA for MIC ≤ 4 mg/L for 40% fT > MIC, but individual dose adjustments are needed for 100% fT > MIC.
PubMed: 38786147
DOI: 10.3390/antibiotics13050419 -
Antibiotics (Basel, Switzerland) May 2024Co-infection with carbapenem-resistant (CRKP) and (CRPA) is associated with poor outcomes and historically relied on combination therapy with toxic agents for...
Co-infection with carbapenem-resistant (CRKP) and (CRPA) is associated with poor outcomes and historically relied on combination therapy with toxic agents for management. However, several novel β-lactam/β-lactamase inhibitor combination agents have been developed, offering potential monotherapy options. Here, we compare the in vitro activity of ceftazidime-avibactam (CZA), imipenem-relebactam (IRL), and meropenem-vaborbactam (MVB) against both CRKP and CRPA clinical isolates. Minimum inhibitory concentrations (MICs) for each agent were determined using broth microdilution. Carbapenemase gene detection was performed for representative isolates of varying carbapenem resistance phenotypes. IRL demonstrated excellent activity against CRKP and CRPA with susceptibility rates at 95.8% and 91.7%, respectively. While CZA and MVB showed comparable susceptibility to IRL against CRKP (93.8%), susceptibility of CRPA to CZA was modest at 79.2%, whereas most CRPA strains were resistant to MVB. Of the 35 CRKP isolates tested, 91.4% (32/35) carried a gene. Only 1 of 37 (2.7%) CRPA isolates tested carried a gene, which conferred phenotypic resistance to all three agents. None of the CRKP strains were cross-resistant to all three agents. Source of infection and co-infection did not significantly influence antimicrobial activity for IRL and CZA; none of the CRPA isolates from co-infected patients were susceptible to MVB. Our results suggest that novel β-lactam agents with antipseudomonal activity and stability against carbapenemases, such as IRL and CZA, offer potential monotherapy options for the treatment of co-infection involving both CRKP and CRPA, but not MVB.
PubMed: 38786144
DOI: 10.3390/antibiotics13050416