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Microorganisms Aug 2023The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel...
The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor that has demonstrated activity against isolates producing class A, C, and D β-lactamases. Here-in, we evaluated the in vitro activity of CZA and comparator antimicrobial agents against 858 CRE isolates, arising from the Southeast Asian region, collected from a large tertiary hospital in Singapore. These CRE isolates mainly comprised (50.5%), (29.4%), and complex (17.1%). Susceptibility rates to levofloxacin, imipenem, meropenem, doripenem, aztreonam, piperacillin/tazobactam, cefepime, tigecycline, and polymyxin B were low. CZA was the most active β-lactam agent against 68.9% of the studied isolates, while amikacin was the most active agent among all comparator antibiotics (80% susceptibility). More than half of the studied isolates (51.4%) identified were carbapenemase (KPC)-2 producers, 25.9% were New Delhi metallo-β-lactamase (NDM) producers, and Oxacillinase (OXA)-48-like producers made up 10.7%. CZA was the most active β-lactam agent against KPC-2, OXA-48-like, and Imipenemase (IMI) producers (99.3% susceptible; MIC: ≤1/2 mg/L). CZA had excellent activity against the non-carbapenemase-producing CRE (91.4% susceptible; MIC: ≤1/8 mg/L). Expectedly, CZA had no activity against the metallo-β-lactamases (MBL)-producing CRE (NDM- and Imipenemase MBL (IMP) producers; 27.2% isolates), and the carbapenemase co-producing CRE (NDM + KPC, NDM + OXA-48-like, NDM + IMP; 3.0% isolates). CZA is a promising addition to our limited armamentarium against CRE infections, given the reasonably high susceptibility rates against these CRE isolates. Careful stewardship and rational dosing regimens are required to preserve CZA's utility against CRE infections.
PubMed: 37764002
DOI: 10.3390/microorganisms11092158 -
Antibiotics (Basel, Switzerland) Dec 2023This study was designed to evaluate the response of antibiotic-resistant to food preservative-related stresses, such as lactic acid and sodium chloride (NaCl). cells...
This study was designed to evaluate the response of antibiotic-resistant to food preservative-related stresses, such as lactic acid and sodium chloride (NaCl). cells were exposed to 1 µg/mL of ciprofloxacin (CIP), 0.2% lactic acid (LA), 6% NaCl, CIP followed by LA (CIP-LA), and CIP followed by NaCl (CIP-NaCl). The untreated cells were the control (CON). All treatments were as follows: CON, CIP, LA, NaCl, CIP-LA, and CIP-NaCl. The phenotypic heterogeneity was evaluated by measuring the antimicrobial susceptibility, bacterial fluctuation, cell injury, persistence, and cross-resistance. The CIP, CIP-LA, and CIP-NaCl groups were highly resistant to ciprofloxacin, showing MIC values of 0.70, 0.59, and 0.54 µg/mL, respectively, compared to the CON group (0.014 µg/mL). The susceptibility to lactic acid was not changed after exposure to NaCl, while that to NaCl was decreased after exposure to NaCl. The Eagle phenomenon was observed in the CIP, CIP-LA, and CIP-NaCl groups, showing Eagle effect concentrations (EECs) of more than 8 µg/mL. No changes in the MBCs of lactic acid and NaCl were observed in the CIP, LA, and CIP-LA groups, and the EECs of lactic acid and NaCl were not detected in all treatments. The bacterial fluctuation rates of the CIP-LA and CIP-NaCl groups were considerably increased to 33% and 41%, respectively, corresponding to the injured cell proportions of 82% and 89%. CIP-NaCl induced persister cells as high as 2 log cfu/mL. The LA and NaCl treatments decreased the fitness cost. The CIP-NaCl treatment showed positive cross-resistance to erythromycin (ERY) and tetracycline (TET), while the LA and NaCl treatments were collaterally susceptible to chloramphenicol (CHL), ciprofloxacin (CIP), piperacillin (PIP), and TET. The results provide new insight into the fate of antibiotic-resistant during food processing and preservation.
PubMed: 38136736
DOI: 10.3390/antibiotics12121702 -
and activity of cefiderocol against spp. and complex, including carbapenem-non-susceptible isolates.Antimicrobial Agents and Chemotherapy Dec 2023spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the...
spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the antibacterial activity of the siderophore antibiotic cefiderocol against spp. and Bcc isolates with that of other approved antibacterial drugs, including ceftazidime-avibactam, ciprofloxacin, colistin, imipenem-relebactam, and meropenem-vaborbactam. Isolates were collected in the SIDERO multinational surveillance program. Among 334 spp. isolates [76.6% from respiratory tract infections (RTIs)], cefiderocol had minimum inhibitory concentration (MIC) of 0.06/0.5 µg/mL overall and 0.5/4 µg/mL against 52 (15.6%) carbapenem-non-susceptible (Carb-NS) isolates. Eleven (3.3%) spp. isolates overall and 6 (11.5%) Carb-NS isolates were not susceptible to cefiderocol. Among 425 Bcc isolates (73.4% from RTIs), cefiderocol had MIC of ≤0.03/0.5 µg/mL overall and ≤0.03/1 µg/mL against 184 (43.3%) Carb-NS isolates. Twenty-two (5.2%) Bcc isolates overall and 13 (7.1%) Carb-NS isolates were not susceptible to cefiderocol. Cumulative MIC distributions showed cefiderocol to be the most active of the agents tested against both spp. and Bcc. In a neutropenic murine lung infection model and a humanized pharmacokinetic immunocompetent rat lung infection model, cefiderocol showed significant bactericidal activity against two meropenem-resistant strains compared with untreated controls ( < 0.05) and vehicle-treated controls ( < 0.05), respectively. Meropenem, piperacillin-tazobactam, ceftazidime, and ciprofloxacin comparators showed no significant activity in these models. The results suggest that cefiderocol could be a possible treatment option for RTIs caused by spp. and Bcc.
Topics: Rats; Animals; Mice; Cefiderocol; Meropenem; Carbapenems; Cephalosporins; Burkholderia cepacia complex; Achromobacter; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Ceftazidime; Respiratory Tract Infections; Ciprofloxacin; Microbial Sensitivity Tests
PubMed: 37971240
DOI: 10.1128/aac.00346-23 -
Microbiology Spectrum Aug 2023Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to...
Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the β-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate β-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed. Bloodstream infection (BSI) caused by P. aeruginosa is related with an elevated morbidity and mortality in neutropenic patients. For this reason, optimal antipseudomonal coverage has been the basis of all historical recommendations in the empirical treatment of febrile neutropenia. However, in recent years the emergence of multiple types of antibiotic resistances has posed a challenge in treating infections caused by this microorganism. In our study we postulated that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines. This observation is associated with frequent IEAT and increased mortality. Consequently, there is a need for a new therapeutic strategy.
Topics: Humans; Anti-Bacterial Agents; Pseudomonas aeruginosa; Cohort Studies; Retrospective Studies; Pseudomonas Infections; Bacteremia; Meropenem; Hematologic Neoplasms; Sepsis
PubMed: 37367629
DOI: 10.1128/spectrum.00674-23 -
Briefings in Bioinformatics Mar 2024The advent of rapid whole-genome sequencing has created new opportunities for computational prediction of antimicrobial resistance (AMR) phenotypes from genomic data....
The advent of rapid whole-genome sequencing has created new opportunities for computational prediction of antimicrobial resistance (AMR) phenotypes from genomic data. Both rule-based and machine learning (ML) approaches have been explored for this task, but systematic benchmarking is still needed. Here, we evaluated four state-of-the-art ML methods (Kover, PhenotypeSeeker, Seq2Geno2Pheno and Aytan-Aktug), an ML baseline and the rule-based ResFinder by training and testing each of them across 78 species-antibiotic datasets, using a rigorous benchmarking workflow that integrates three evaluation approaches, each paired with three distinct sample splitting methods. Our analysis revealed considerable variation in the performance across techniques and datasets. Whereas ML methods generally excelled for closely related strains, ResFinder excelled for handling divergent genomes. Overall, Kover most frequently ranked top among the ML approaches, followed by PhenotypeSeeker and Seq2Geno2Pheno. AMR phenotypes for antibiotic classes such as macrolides and sulfonamides were predicted with the highest accuracies. The quality of predictions varied substantially across species-antibiotic combinations, particularly for beta-lactams; across species, resistance phenotyping of the beta-lactams compound, aztreonam, amoxicillin/clavulanic acid, cefoxitin, ceftazidime and piperacillin/tazobactam, alongside tetracyclines demonstrated more variable performance than the other benchmarked antibiotics. By organism, Campylobacter jejuni and Enterococcus faecium phenotypes were more robustly predicted than those of Escherichia coli, Staphylococcus aureus, Salmonella enterica, Neisseria gonorrhoeae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Streptococcus pneumoniae and Mycobacterium tuberculosis. In addition, our study provides software recommendations for each species-antibiotic combination. It furthermore highlights the need for optimization for robust clinical applications, particularly for strains that diverge substantially from those used for training.
Topics: Phenotype; Anti-Bacterial Agents; Machine Learning; Drug Resistance, Bacterial; Computational Biology; Genome, Bacterial; Genome, Microbial; Humans; Bacteria
PubMed: 38706320
DOI: 10.1093/bib/bbae206 -
Clinical Nephrology. Case Studies 2023We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of...
PURPOSE
We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition.
OBSERVATIONS
We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis.
CONCLUSION AND IMPORTANCE
These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).
PubMed: 38169875
DOI: 10.5414/CNCS111088 -
Cirugia Pediatrica : Organo Oficial de... Oct 2023In spite of the increase in the prevalence of cholelithiasis in the last decades, no recommendations regarding the best treatment of acute calculous cholecystitis (AC)...
INTRODUCTION
In spite of the increase in the prevalence of cholelithiasis in the last decades, no recommendations regarding the best treatment of acute calculous cholecystitis (AC) in Pediatrics have been developed.
CLINICAL CASE
4-year-old, 20kg male patient with no significant history referred to our institution as a result of abdominal sepsis. The blood count showed leukocytosis, with normal hemoglobin and bilirubin levels, and a normal liver function. The abdominal ultrasonography revealed cholelithiasis, gallbladder hydrops, and an inflammatory process compatible with appendicular plastron. In the diagnostic laparoscopy, the appendix was macroscopically normal, and acute cholecystitis was observed. Given the patient's situation, and in cooperation with the General Surgery Department, laparoscopic cholecystectomy was carried out. The patient recovered uneventfully on hospitalization day 5 under piperacillin-tazobactam treatment.
DISCUSSION
There are no recommendations regarding AC treatment in children. In septic patients, cooperation between general and pediatric surgeons allows urgent cholecystectomy to be considered as a safe option.
Topics: Humans; Male; Child; Child, Preschool; Cholecystectomy, Laparoscopic; Cholecystitis, Acute; Cholelithiasis; Cholecystectomy; Laparoscopy
PubMed: 37818901
DOI: 10.54847/cp.2023.04.15 -
PloS One 2023This study described the demographic characteristics, clinical presentation, treatment, and outcomes of solid organ transplant recipients who were admitted to our center... (Observational Study)
Observational Study
OBJECTIVES
This study described the demographic characteristics, clinical presentation, treatment, and outcomes of solid organ transplant recipients who were admitted to our center for infection. It also determined factors associated with a poor outcome, and compares early and late period infections.
METHODS
In this retrospective observational study, conducted at a tertiary care center in France between October 2017 and March 2019, infectious outcomes of patients with solid organ transplant where studied.
RESULTS
A total of 104 patients were included with 158 hospitalizations for infection. Among these 104 patients, 71 (68%) were men. The median age was 59 years old. The most common symptoms on admission were fever (66%) and chills (31%). Lower respiratory tract infections were the most common diagnosis (71/158 hospitalizations). Urinary tract infections were frequently seen in kidney transplant recipients (25/60 hospitalizations). One or more infectious agents were isolated for 113 hospitalizations (72%): 70 bacteria, 36 viruses and 10 fungi, with predominance of gram-negative bacilli (53 cases) of which 13 were multidrug-resistant. The most frequently used antibiotics were third generation cephalosporins (40 cases), followed by piperacillin-tazobactam (26 cases). We note that 25 infections (16%) occurred during the first 6 months (early post-transplant period). Patients admitted during the early post-transplant period were more often on immunosuppressive treatment with prednisone (25/25 VS 106/133) (p = 0.01), mycophenolic acid (22/25 VS 86/133) (p = 0.03), presented for an urinary tract infection (10/25 VS 25/133) (p = 0.04) or a bacterial infection (17/25 VS 53/133) (p = 0.01). Patients with later infection had more comorbidities (57/83 VS 9/21) (p = 0.03), cancer (19/83 VS 0/21) (p = 0.04) or were on treatment with everolimus (46/133 VS 0/25) (p = 0.001). During 31 hospitalizations (20%), patients presented with a serious infection requiring intensive care (n = 26; 16%) or leading to death (n = 7; 4%). Bacteremia, pulmonary and cardiac complications were the main risk factors associated with poor outcome.
CONCLUSION
Infections pose a significant challenge in the care of solid organ transplant patients, particularly those with comorbidities and intensive immunosuppression. This underscores the crucial importance of continuous surveillance and epidemiologic monitoring within this patient population.
Topics: Male; Humans; Adult; Middle Aged; Female; Paris; Retrospective Studies; Organ Transplantation; Bacterial Infections; Anti-Bacterial Agents; Urinary Tract Infections
PubMed: 37797039
DOI: 10.1371/journal.pone.0291860 -
Frontiers in Cellular and Infection... 2023The colonization of the oral cavity by potentially pathogenic antimicrobial-resistant bacteria in adolescents and its consequences is very poorly understood. The present...
INTRODUCTION
The colonization of the oral cavity by potentially pathogenic antimicrobial-resistant bacteria in adolescents and its consequences is very poorly understood. The present study focused on the occurrence of oral colonization by Gram-negative bacilli (GNB) and their multidrug resistance, including the production of extended-spectrum β-lactamases (ESBLs) and carbapenemases, among healthy adolescents and risk factors associated with GNB colonization.
MATERIALS AND METHODS
This study was conducted as part of "A program for the early detection of risk factors for lifestyle diseases SOPKARD-Junior" (SOPKARD-Junior). Oral samples were collected from 182 adolescents from four public elementary schools in Sopot, Poland, aged 13-14 years. Bacterial strains were identified by the MALDI-TOF MS method. Screening of antimicrobial resistance was performed using a disk diffusion method. The NG-Test CARBA-5 was used to detect and differentiate the five most widely distributed carbapenemases. Demographic and clinical data were collected and statistical analysis of risk factors was performed.
RESULTS
A total of 68 out of 182 (37.4%) healthy adolescents was documented oral colonization with Gram-negative bacilli, including 50/182 (27.5%) multidrug resistant (MDR-GNB) strains. Over 60% of oral carriage concerned three main genera spp., spp., and spp., which were detected in 22.1%, 19.1%, and 19.1% of participants, respectively. spp., , spp., spp., spp., spp., and spp. were also isolated. The antimicrobial resistance to ampicillin (100%), ceftazidime (69.1%), meropenem (60.3%), gentamycin (60.3%), piperacillin/tazobactam (52.9%), and piperacillin (45.6%) were the most common. Among 73.5% GNB strains multidrug resistance was observed, including all spp. strains. Among MDR-GNB, 30.4% were resistant to four groups of antibiotics, half of the MDR spp. strains were resistant to 10 groups of antibiotics. Extended-spectrum β-lactamases were produced by , spp., and spp. (7.4%). Colonization by ESBLs-positive GNB strains was significantly associated with recurrent respiratory infections, nasal congestion, and bronchitis (p<0.05).
CONCLUSION
Our study revealed high oral carriage of multi-drug resistant Gram-negative bacilli in healthy adolescents and the association of ESBL-producing strains with respiratory infections. Further studies on oral colonization with GNB are necessary due to the possibility of distinct infections and the acquisition of antibiotic resistance by resident microbiota.
Topics: Adolescent; Humans; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Gram-Negative Bacteria; beta-Lactamases; Piperacillin; Respiratory Tract Infections; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests
PubMed: 38035342
DOI: 10.3389/fcimb.2023.1265777 -
Infection, Genetics and Evolution :... Aug 2023Studies on antimicrobial resistance (AMR) profiles and epidemiological affirmation for AMR transmission are limited in fisheries and aquaculture settings. Since 2015,...
Studies on antimicrobial resistance (AMR) profiles and epidemiological affirmation for AMR transmission are limited in fisheries and aquaculture settings. Since 2015, based on Global Action Plan on AMR by World Health Organization (WHO) and World Organization for Animal Health (OIE), several initiatives have been under taken to enhance the knowledge, skills and capacity to establish AMR trends through surveillance and strengthening of epidemiological evidence. The focus of this study was to determine the prevalence of antimicrobial resistance (AMR), its resistance profiles and molecular characterization with respect to phylogroups, antimicrobial resistance genes (ARGs), virulence genes (VGs), quaternary ammonium compounds resistance (QAC) genes and plasmid typing in retail market fishes. Pulse field gel electrophoresis (PFGE) to understand the genetic lineage of the two most important Enterobacteriaceae members, E. coli and Klebsiella sp. was performed. 94 fish samples were collected from three different sites viz., Silagrant (S1), Garchuk (S2) and North Guwahati Town Committee (NGTC) Region (S3) in Guwahati, Assam. Out of the 113 microbial isolates from the fish samples, 45 (39.82%) were E. coli; 23 (20.35%) belonged to Klebsiella genus. Among E. coli, 48.88% (n = 22) of the isolates were alerted by the BD Phoenix M50 instrument as ESBL, 15.55% (n = 7) as PCP and 35.55% (n = 16) as non-ESBL. E. coli (39.82%) was the most prevalent pathogen among the Enterobacteriaceae members screened and showed resistance to ampicillin (69%) followed by cefazoline (64%), cefotaxime (49%) and piperacillin (49%). In the present study, 66.66% of E. coli and 30.43% of Klebsiella sp. were categorized as multi drug resistance (MDR) bacteria. CTX-M-gp-1, with CTX-M-15 variant (47%), was the most widely circulating beta-lactamase gene, while other ESBL genes bla (7%), bla (2%) and bla (2%) were also identified in E. coli. Out of the 23 isolates of Klebsiella, 14(60.86%) were ampicillin (AM)-resistant (11(47.82%) K. oxytoca, 3(13.04%) K. aerogenes), whereas 8(34.78%) isolates of K. oxytoca showed intermediate resistance to AM. All Klebsiella isolates were susceptible to AN, SCP, MEM and TZP, although two K. aerogenes were resistant to imipenem. DHA and LAT genes were detected, respectively, in 7(16%) and 1(2%) of the E. coli strains while a single K. oxytoca (4.34%) isolate carried MOX, DHA and bla genes. The fluoroquinolone resistance genes identified in E. coli included qnrB (71%), qnrS (84%), oqxB (73%) and aac(6)-Ib-cr (27%); however, in Klebsiella, these genes, respectively, had a prevalence of 87%, 26%, 74% and 9%. The E. coli isolates belonged to phylogroup A(47%), B1(33%) and D(14%). All of the 22(100%) ESBL E. coli had chromosome-mediated disinfectant resistance genes viz., ydgE, ydgF, sugE(c), mdfA while 82% of ESBL E. coli had emrE. Among the non-ESBL E. coli isolates, 87% of them showed the presence of ydgE, ydgF and sugE(c) genes, while 78% of the isolates had mdfA and 39% had emrE genes respectively. 59% of the ESBL and 26% of the non-ESBL E. coli had showed the presence of qacEΔ1. The sugE(p) was present in 27% of the ESBL-producing E. coli and in 9% of non-ESBL isolates. Out of the 3 ESBL-producing Klebsiella isolates, 2(66.66%) K. oxytoca isolates were found harboring plasmid-mediated qacEΔ1 gene while one (33.33%) K. oxytoca isolate had sugE(p) gene. IncFI was the most prevalent plasmid type detected in the isolates studied, with A/C (18%), P (14%), X, Y (9% each) and I1-Iγ (14%, 4%). 50% (n = 11) of the ESBL and 17% (n = 4) of the non-ESBL E. coli isolates harboured IncFIB and 45% (n = 10) ESBL and one (4.34%) non-ESBL E. coli isolates harboured IncFIA. Dominance of E. coli over other Enterobacterales and diverse phylogenetic profiles of E. coli and Klebsiella sp. suggests the possibility of contamination and this may be due to compromised hygienic practices along the supply chain and contamination of aquatic ecosystem. Continuous surveillance in domestic markets must be a priority in addressing antimicrobial resistance in fishery settings and to identify any unwarranted epidemic clones of E. coli and Klebsiella that can challenge public health sector.
Topics: Animals; Escherichia coli; Klebsiella; Anti-Bacterial Agents; Genotype; Phylogeny; Ecosystem; beta-Lactamases; Ampicillin; Microbial Sensitivity Tests
PubMed: 37245778
DOI: 10.1016/j.meegid.2023.105446