Search Results (72)

Antimicrobial resistance (AMR) is a growing global health threat, with wild birds increasingly recognized as potential reservoirs of resistant pathogens and as sentinels of environmental AMR. This study investigated the occurrence and AMR profiles of Gram-negative bacteria isolated from wild birds that died at the Wildlife Rescue Center in Vanzago, Lombardy, in 2024. Cloacal swabs were collected from 112 birds representing various ecological categories. A total of 157 Gram-negative bacteria were isolated and identified, including clinically relevant genera and species, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Salmonella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Antimicrobial susceptibility testing revealed resistance to first-line and critically important antimicrobials, including those exclusively authorized for human use. Notably, a phenotype compatible with Extended-Spectrum Beta-Lactamase (ESBL) production was detected in four out of ten (40%) K. pneumoniae isolates. In addition, 20 out of the 157 (12.7%) isolated bacteria phenotypically exhibited a resistance profile indicative of AmpC beta-lactamase (AmpC) production, including Enterobacter spp. and P. aeruginosa. Resistance patterns were particularly interesting in birds with carnivorous, scavenging, or migratory-associated behaviors. These findings highlight the role of wild birds in the ecology and dissemination of antimicrobial-resistant bacteria (ARB) and highlight the need for wildlife-based AMR monitoring programs as part of a One Health approach. Full article

Objectives: Plasmid-mediated AmpC beta-lactamases represent a growing clinical concern in Enterobacterales, with challenges in diagnostic approaches, limited data on clinical outcomes, and our incomplete understanding of their regulatory mechanisms warranting the need for further investigation. Methods: This retrospective study examined the genomic and clinical characteristics of cefoxitin-non-susceptible, ceftriaxone-susceptible Escherichia coli and Klebsiella pneumoniae bloodstream isolates collected from a tertiary hospital in Singapore. Whole-genome sequencing was performed to detect ampC genes, subtypes, and associated regulatory elements. Results: Among 108 cefoxitin-non-susceptible isolates, only 15 (13.9%) harboured plasmid-mediated ampC, suggesting that cefoxitin non-susceptibility alone in ceftriaxone susceptible isolates was not predictive of ampC carriage. All plasmid-ampC isolates were from the bla_DHA-1 subtype and carried ampR, a known transcriptional regulator of inducible beta-lactamase expression. Notably, five non-ampC carrying Klebsiella isolates displayed truncations in ompK35 and ompK36, which could potentially contribute to reduced cefoxitin susceptibility via porin loss. Conclusions: These findings underscore the limited diagnostic utility of cefoxitin susceptibility testing for detecting plasmid-mediated ampC producers and highlight the clinical relevance of regulatory genes such as ampR in mediating inducible resistance. The routine incorporation of molecular diagnostics or genome sequencing may be necessary to improve detection accuracy and inform antimicrobial stewardship strategies. Full article

Background/Objectives: The widespread use of antibiotics in animal husbandry has led to an increase in antimicrobial-resistant Escherichia coli, particularly strains producing extended-spectrum β-lactamases (ESBL) and AmpC β-lactamases. This study aimed to isolate and characterize such strains from fecal samples of broiler chickens (n = 71) and slaughtered turkeys (n = 31) in northwestern Romania. Methods: Antimicrobial susceptibility testing and PCR were used to evaluate phenotypic resistance patterns and detect the presence of resistance genes (AmpC, blaZ, and blaTEM). Results: The results showed that 55% of turkey and 61% of broiler isolates were presumptive ESBL/AmpC producers. Among all isolates, 50% were classified as extensively drug-resistant (XDR), 44% as multidrug-resistant (MDR), and only 6% were fully susceptible. Gene detection revealed an overall prevalence of 44.2% for AmpC, 72.7% for blaZ, and 58.1% for blaTEM, yielding a total penetrance of 51.09%. The diagnostic odds ratio (DOR) values, ranging from 0.67 to 81, suggest the efficacy of the antibiotic susceptibility testing method used in detecting the presence of these resistance genes. Conclusion: Overall, these findings highlight a significant burden of antimicrobial-resistant, poultry-associated E. coli strains, warranting stricter antimicrobial stewardship. Full article

Antibiotic resistance is increasing at an alarming rate worldwide, in large part due to their misuse and improper disposal. Antibiotics administered to treat human and animal diseases, including feed supplements for the treatment or prevention of disease in farm animals, have contributed greatly to the emergence of a multitude of antibiotic-resistant pathogens. Shewanella is one of many bacteria that have developed antibiotic resistance, and in some species, multiple-antibiotic resistance (MAR). Shewanella is a rod-shaped, Gram-negative, oxidase-positive, and H₂S-producing bacterium that is naturally found in the marine environment. In humans, Shewanella spp. can cause skin and soft tissue infections, septicemia, cellulitis, osteomyelitis, and ear and wound infections. Some Shewanella have been shown to be resistant to a variety of antibiotics, including beta-lactams, aminoglycoside, quinolones, third- or fourth-generation cephalosporins, and carbapenems, due to the presence of genes such as the bla_OXA-class D beta-lactamase-encoding gene, bla_AmpC-class-C beta-lactamase-encoding gene, and the qnr gene. Bacteria can acquire and transmit these genes through different horizontal gene-transmission mechanisms such as transformation, transduction, and conjugation. The genes for antibiotic resistance are present on Shewanella chromosomes and plasmids. Apart from this, heavy metals such as arsenic, mercury, cadmium, and chromium can also increase antibiotic resistance in Shewanella due to co-selection processes such as co-resistance, cross resistance, and co-regulation mechanisms. Antibiotics and drugs enter Shewanella spp. through pores or gates in their cell wall and may be ejected from the bacteria by efflux pumps, which are the first line of bacterial defense against antibiotics. Multiple-drug resistant Shewanella can be particularly difficult to control. This review focuses on the phenotypic and genomic characteristics of Shewanella that are involved in the increase in antimicrobial resistance in this bacterium. Full article

Background: Mapping the local etiology and susceptibility of common pathogens causing complicated urinary tract infection (cUTI) is important for promoting evidence-based antimicrobial prescribing. Evaluating the prevalence of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase (AmpC), and carbapenemase-producing Enterobacterales (CPEs) is equally important as it informs treatment guidelines and empiric management. Whole genome sequencing (WGS) enhances antimicrobial resistance (AMR) surveillance by complementing phenotypic antimicrobial susceptibility testing, offering deeper insights into resistance mechanisms, transmissions, and evolutions. Integrating it into routine AMR monitoring can significantly improve global efforts to combat antimicrobial resistance. Methods: Antimicrobial susceptibility profiles of isolates from cUTI were collected from patients presenting with Sultan Qaboos University Hospital, Muscat and Suhar Hospital, Suhar, Oman. Automated systems as well as manual methods were used for detection of ESBL, AmpC, and CPE. ESBLs, AmpC β-lactamases, and CPEs were further detected by manual methods: double-disk synergy test for ESBL; disk approximation assay and D69C AmpC detection set for AmpC, and mCIM and KPC/IMP/NDM/VIM/OXA-48 Combo test kit for CPE. WGS was carried out in 11 FOX-resistant E. coli and (22 carbapenem-resistant K. pneumoniae) isolates with varying susceptibilities to identify circulating clades, AMR genes, and plasmids. Bioinformatic analysis was performed using online tools. Results: The susceptibility patterns of E. coli from cUTI were as follows: nitrofurantoin (96%), fosfomycin (100%), fluoroquinolones (44%), aminoglycosides (93%), piperacillin-tazobactam (95%), and carbapenems (98%). In comparison, susceptibility rates of K. pneumoniae were far lower: nitrofurantoin (38%), fosfomycin (89%), aminoglycosides (82%), piperacillin-tazobactam (72%), and carbapenems (83%). K. pneumoniae, however, was more susceptible to fluoroquinolones at 47% in comparison to E. coli. The prevalence of ESBL among E. coli and K. pneumoniae was 37.2% and CRE was 6.2% while the estimated prevalence of AmpC was 5.4%. It was observed that E. coli was the predominant ESBL and AmpC producer, while K. pneumoniae was the major carbapenem-resistant Enterobacterales (CREs) producer. No predominant multi-locus sequence typing (MLST) lineage was observed in AmpC-producing E. coli with nine E. coli MLST lineages being identified from eleven isolates: ST-10, ST-69, ST-77, ST-131, ST-156, ST-167, ST-361, ST-1125, and ST-2520. On the other hand, a less diverse MLST spectrum (ST-2096, ST-231, ST-147, ST-1770, and ST-111) was observed in the CRE K. pneumoniae. Among the five MLST lineages, ST-2096 (twelve isolates) and ST-147 (seven isolates) predominated. WGS revealed that DHA-1 was the predominant plasmid-mediated AmpC gene in E. coli, while OXA-232 and NDM-5 were the most common carbapenemase genes in K. pneumoniae. All E. coli DHA-1-positive isolates co-harbored the quinolone resistance gene qnrB4 and the sulfonamide resistance gene sul1 while no aminoglycoside resistance genes were detected. The majority of CPE CRE K. pneumoniae carried other β-lactamase genes, such as blaCTX-M-15, blaSHV, and blaTEM; all co-harbored the quinolone resistance gene OqxAB; and 77% carried the aminoglycoside resistance gene armA. Conclusions: Our results suggest that fosfomycin is an excellent empiric choice for treating complicated cystitis caused by both E. coli and K. pneumoniae, while nitrofurantoin is an appropriate choice for E. coli cystitis but not for K. pneumoniae. Aminoglycosides and piperacillin-tazobactam are excellent intravenous alternatives that spare carbapenems. DHA-1 was the predominant AmpC in E. coli, while OXA-232 and NDM-5 were the predominant carbapenemases in K. pneumoniae. In AmpC-producing E. coli, no MLST predominated, suggesting a significant flux in E. coli with lack of stable clades in this region. In contrast, ST-2096 and ST-147 predominated in CRE Klebsiella pneumoniae, suggesting a stable circulation of these in Oman. WGS profiling provides a deeper understanding of the genetic basis of resistance and enhances surveillance and offers comprehensive insights into pathogen evolution and transmission patterns. Full article

Background/Objectives: Motile aeromonads are ubiquitous aquatic Gram-negative opportunistic pathogens with environmental, animal, aquatic, and human health implications. Methods: Motile aeromonads were isolated from village pond water samples (n = 100) of the Hisar district of Haryana state in India. Selective isolation and enumeration were followed by biochemical and genotypic identification using gyrB gene; evaluation of seven putative virulence factors and antimicrobial resistance studies and determination of extended spectrum beta lactamase (ESBL) and AmpC beta lactamase (ACBL) enzyme-producing abilities took place. Results: The viable counts of motile aeromonads varied from 1.6 × 10² CFU/mL to 1.2 × 10⁸ CFU/mL. Six species of Aeromonas were identified with high prevalence of A. veronii (74.7%), followed by A. caviae (8.9%), A. hydrophila (7.6), A. jandaei (5%), A. sobria (2.5%), and A. dhakensis (1.3%). PCR amplification of seven genes related to virulence indicated that the majority of the isolates were positive for enolase (eno, 98%), cytotoxic enterotoxin (act, 88%), and hemolysin (asa1, 86%). Many isolates were also positive for type III secretion system inner membrane component (ascV, 53%), ADP-ribosylating toxin (aexT, 47%), and extracellular hemolysin (ahh1, 4%). The antimicrobial resistance (AMR) profile of the isolated Aeromonas isolates indicated the high resistance observed to nalidixic acid (40.2%), cefoxitin (33%), and imipenem (6.2%). In addition, the occurrence of 10.3% ESBL, 32% ACBL, and 29.9% multi-drug resistant (MDR) isolates is alarming. Phylogenetic analysis of gyrB sequences of A. veronii isolates (n = 59) together with GenBank sequences of A. veronii from different geographical regions of the world indicated high genotypic diversity. Conclusions: the village aquaculture ponds in Hisar district have a high occurrence of MDR A. veronii, A. hydrophila, and A. caviae, posing significant animal and public health concern. Full article

Ceftazidime–avibactam (CZA) is a potent broad-spectrum drug combination covering extended-spectrum β-lactamases, AmpC, and carbapenemases of class A and D, OXA-48-type producers. Rapid antimicrobial susceptibility testing is crucial for the timely de-escalation/escalation of therapy. We evaluate CZA susceptibility using the CE-IVD FASTgramneg kit (FASTinov^®), a ground-breaking 2 h assay, based on flow cytometry technology for antimicrobial susceptibility testing. The assay involved rapid bacterial extraction and purification from positive blood cultures (PBCs), followed by a 1 h 37 °C incubation and flow cytometry analysis (Cytoflex, Beckman-Coulter). The susceptibility report was generated using a proprietary software and interpreted using EUCAST and CLSI 2024 criteria. Sensitivity and specificity were calculated against a reference standardized method (disk diffusion) according to ISO20776-2:2021. Overall, 135 Enterobacterales and 73 Pseudomonas aeruginosa isolates were studied. Thirty-four isolates were resistant to CZA, including six P. aeruginosa and 28 Enterobacterales (24 metallo-beta-lactamase producers, three KPC variants, and one co-producing KPC+NDM). Sensitivity and specificity reached 100% when using EUCAST and CLSI criteria compared with the reference method. The FASTinov ultra-rapid susceptibility assay for CZA demonstrated excellent results, potentially enabling de-escalation/escalation even before the second dose. Combining the speed of a molecular assay with the comprehensive information of a phenotypic test offers valuable insights for treatment decisions. Full article

AmpC enzymes are a class of beta-lactamases produced by Gram-negative bacteria, including several Enterobacterales. When produced in sufficient amounts, AmpCs can hydrolyze third-generation cephalosporins (3GCs) and piperacillin/tazobactam, causing resistance. In Enterobacterales, the AmpC gene can be chromosomal- or plasmid-encoded. Some species, particularly Enterobacter cloacae complex, Klebsiella aerogenes, and Citrobacter freundii, harbor an inducible chromosomal AmpC gene. The expression of this gene can be derepressed during treatment with a beta-lactam, leading to AmpC overproduction and the consequent emergence of resistance to 3GCs and piperacillin/tazobactam during treatment. Because of this phenomenon, the use of carbapenems or cefepime is considered a safer option when treating these pathogens. However, many areas of uncertainty persist, including the risk of derepression related to each beta-lactam; the role of piperacillin/tazobactam compared to cefepime; the best option for severe or difficult-to-treat cases, such as high-inoculum infections (e.g., ventilator-associated pneumonia and undrainable abscesses); the role of de-escalation once clinical stability is obtained; and the best treatment for species with a lower risk of derepression during treatment (e.g., Serratia marcescens and Morganella morganii). The aim of this review is to collate the most relevant information about the microbiological properties of and therapeutic approach to AmpC-producing Enterobacterales in order to inform daily clinical practice. Full article

We analyzed the whole genome sequences (WGS) and antibiograms of 35 Enterobacter isolates, including E. hormaechei and E. asburiae, and the recently described E. bugandensis, E. kobei, E. ludwigii, and E. roggenkampii species. Isolates were obtained from human blood and urinary tract infections in patients in the United States. Our goal was to understand the genetic diversity of antimicrobial resistance genes and virulence factors among the various species. Thirty-four of 35 isolates contained an AmpC class bla_ACT allele; however, the E. roggenkampii isolate contained bla_MIR-5. Of the six Enterobacter isolates resistant to ertapenem, imipenem, and meropenem, four harbored a carbapenemase gene, including bla_KPC or bla_NDM. All four isolates were mCIM-positive. The remaining two isolates had alterations in ompC genes that may have contributed to the resistance phenotype. Interpretations of cefepime test results were variable when disk diffusion and automated broth microdilution results were compared due to the Clinical Laboratory and Standards Institute use of the “susceptible dose-dependent” classification. The diversity of the bla_ACT alleles paralleled species identifications, as did the presence of various virulence genes. The classification of recently described Enterobacter species is consistent with their resistance gene and virulence gene profiles. Full article

The aim of the present work was to genetically characterise cefotaxime-resistant enterobacteria isolated from community carriers in Bulgaria. In total, 717 faecal samples from children and adults in five medical centres in Sofia, Pleven and Burgas were examined. Antimicrobial susceptibility was evaluated by the disk diffusion method. bla_ESBL or plasmidic AmpC (pAmpC) genes were detected by PCR and sequencing. MLST and ERIC-PCR were used to detect clonal relatedness. Among the faecal samples, 140 cefotaxime-resistant enterobacteria were found. The most frequently detected species was Escherichia coli (77.9%, 109/140 samples), followed by Klebsiella pneumoniae (7.9%, 11/140). Among the isolates, bla_CTX-M-15 (37.1%) was predominant, followed by bla_CTX-M-3 (19.2%), bla_CTX-M-14 (10%), and bla_CTX-M-27 (4.3 %). Genes encoding pAmpC were observed in 11.4% (bla_DHA-1, 16/140) and in 1.4% (bla_CMY-2, 2/140). The frequency of ESBL and pAmpC producers among the subjects was 14.6% and 2.5%, respectively. No carbapenem-resistant isolates were found. Four main clonal complexes (CC131, CC10, CC38, and CC155) were detected among E. coli isolates. The most common type was ST131, phylogroup B2 (16.5%). The increased frequency of ESBL- and pAmpC-producing enterobacteria in the community is a prerequisite for treatment failures of the associated infections and a good background for further studies. Full article

Introduction: Bloodstream infections caused by AmpC-producing Enterobacterales pose treatment challenges due to the risk of AmpC overproduction and treatment failure. Current guidelines recommend carbapenems or cefepime as optimal therapy. We aimed to evaluate empiric and definitive non-carbapenem regimens for these infections. Methods: In a retrospective study from June 2014 to March 2023, adult bacteremic patients with Enterobacter cloacae complex strains and Morganella morganii were evaluated. Demographic, clinical and lab data and outcomes were assessed. Results: The cohort comprised 120 bacteremic patients, 17 receiving empiric carbapenem and 103 non-carbapenem regimens. Both groups had similar Charlson and Norton scores and previous antimicrobial exposure. The most common sources of bacteremia were urinary, abdominal and central-line-associated sources. Empiric non-carbapenem regimens (primarily piperacillin–tazobactam and cephalosporins) were not associated with recurrent bacteremia or 30-day mortality. Definitive regimens included mainly carbapenems (n = 41) and ciprofloxacin (n = 46). Beta-lactams were administered to 25 patients. Recurrent bacteremia and 30-day mortality rates were similar among treatment groups. Ciprofloxacin showed comparable outcomes to carbapenems, however, severity of illness among these patients was lower. Conclusions: Empiric and definitive non-carbapenem regimens for bacteremia with AmpC-producing organisms were not associated with treatment failure or increased 30-day mortality. Ciprofloxacin appears promising for selected, stable patients, potentially enabling early discharge. Full article

Following burn injury, patients are at increased risk of infection and are often cited as having a high incidence of difficult-to-treat pathogens (DTp). The purpose of this study is to determine the incidence of DTp after burn injury, which factors are associated with their development, and subsequent outcomes. This single-center, retrospective study assessed patients with thermal or inhalation injury who had a positive culture resulting in initiation of treatment (i.e., excision, topical, or systemic antimicrobials). Demographic data, pathogen and resistance profiles, and prior exposure to topical and systemic antimicrobials were collected. Pathogens were considered DTp if they were multi-drug-resistant (MDR), extensively drug-resistant (XDR), methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing, AmpC-producing, carbapenem-resistant, difficult-to-treat resistance (DTR) Pseudomonas sp., carbapenem-resistant Acinetobacter baumannii (CRAB), or Stenotrophomonas spp. Sixty-five patients who grew 376 pathogens were included in the final analysis. Two-hundred thirteen (56.7%) pathogens were considered DTp. Prior exposure to 7 of the 11 collected topical antimicrobials and 9 of 11 systemic antimicrobial classes were significantly associated with future development of a DTp. This remained true for six and eight, respectively, after controlling for significant covariates via logistic regression. As there were only four deaths, a Cox-proportional hazard analysis was not feasible. The Kaplan–Meier plot according to DTp revealed a clear divergence in mortality (Log rank p = 0.0583). In this analysis, exposure to topical and systemic antibiotics was associated with the development of DTp. The results from this pilot study will inform the next iteration of multicenter study. Full article

Valley surface water is considered a focal public health concern owing to the presence of multi-drug-resistant bacteria. The distribution of antimicrobial resistance (AMR) bacteria in the surface water is affected by the presence of multiple factors, including antibiotics coming from wastewater discharge or other contaminant sources such as pharmaceuticals, biocides, and heavy metals. Furthermore, there is evidence suggesting that high levels of antibiotic resistance genes (ARGs) can be transferred within bacterial communities under the influence of heavy metal stress. Hence, the primary aim of this study is to investigate the presence of heavy metals and bacterial ARGs in upstream as well as downstream locations of Wadi Hanifah Valley in Riyadh, Saudi Arabia. Sample collection was conducted at eighteen surface water sites within the valley in total. The selection of ARGs was associated with the most common antibiotics, including β-lactam, tetracycline, erythromycin, gentamicin, sulphonamide, chloramphenicol, vancomycin, trimethoprim, and colistin antibiotics, which were detected qualitatively using polymerase chain reaction (PCR) technology. The tested antibiotic resistance genes (ARGs) included (bla_NDM-1 (for the antibiotic class Beta-lactamases), mecA (methicillin-resistant Staphylococcus aureus), tet(M) and tet(B) (for the antibiotic class Tetracycline), ampC (for the antibiotic class Beta-lactamases), vanA (for the antibiotic class vancomycin), mcr-1 (for the antibiotic class colistin), erm(B) (for the antibiotic class erythromycin), aac6′-Ie-aph2-Ia (for the antibiotic class Gentamicin), sulII (for the antibiotic class sulphonamide), catII (for the antibiotic class Chlorophincol), and dfrA1 (for the antibiotic class trimethoprim). Moreover, an assessment of the levels of heavy metals such as lithium (Li), beryllium (Be), chromium (Cr), cobalt (Co), arsenic (As), cadmium (Cd), tin (Sn), mercury (Hg), and lead (Pb) was conducted by using inductively coupled plasma mass spectrometry (ICPMS). According to our findings, the concentrations of sulphonamide, erythromycin, and chloramphenicol ARGs (erm(B), sulII, and catII) were observed to be the most elevated. Conversely, two ARGs, namely mecA and mcr-1, were not detected in the samples. Moreover, our data illustrated a significant rise in ARGs in the bacteria of water samples from the upstream sites as compared with the water samples from the downstream sites of Wadi Hanifah Valley. The mean concentration of Li, Be, Cr, Co, As, Cd, Sn, Hg, and Pb in the water samples was estimated to be 37.25 µg/L, 0.02 µg/L, 0.56 µg/L,0.32 µg/L, 0.93 µg/L, 0.01 µg/L, 200.4 µg/L, 0.027 µg/L, and 0.26 µg/L, respectively, for the selected 18 sites. Furthermore, it was revealed that the concentrations of the screened heavy metals in the water samples collected from various sites did not surpass the maximum limits set by the World Health Organization (WHO). In conclusion, this study offers a concise overview of the presence of heavy metals and ARGs in water samples obtained from the Wadi Hanifah Valley in Riyadh, KSA. Such findings will contribute to the ongoing monitoring and future risk assessment of ARGs spread in surface water. Full article

AmpC beta-lactamases cause resistance to third-generation cephalosporins, including beta-lactamase inhibitors. In Escherichia coli from the German food production chain, the majority of AmpC beta-lactamase activity can be attributed to plasmid-mediated CMY-2 or overproduction of chromosomal AmpC beta-lactamase, but occasionally other enzymes like DHA-1 are involved. This study investigated the prevalence of the AmpC beta-lactamase DHA-1 in ESBL/AmpC-producing E. coli (n = 4706) collected between 2016 and 2021 as part of a German antimicrobial resistance monitoring program along the food chain. Eight isolates (prevalence < 0.2%) were detected and further characterized by PFGE, transformation and conjugation experiments as well as short-read and long-read sequencing. All eight strains harbored bla_DHA-1 together with qnrB4, sul1 and mph(A) resistance genes on an IS26 composite transposon on self-transferable IncFII or IncFIA/FIB/II plasmids. During laboratory experiments, activation of the translocatable unit of IS26-bound structures was observed. This was shown by the variability of plasmid sizes in original isolates, transconjugants or transferred plasmids, and correspondingly, duplications of resistance fragments were found in long-read sequencing. This activation could be artificial due to laboratory handling or naturally occurring. Nevertheless, DHA-1 is a rare AmpC beta-lactamase in livestock and food in Germany, and its dissemination will be monitored in the future. Full article

Introduction: Beta-lactamases are frequently prescribed for Gram-negative bloodstream infections (BSIs). However, chromosomally encoded AmpC-producing Enterobacterales (AE) could overproduce beta-lactamases when exposed to third-generation cephalosporins (3GCs), with a risk of clinical failure. There are few available in vivo data on the subject. Our goal was to assess the potential role of AE as a predictive factor for clinical failure in patients with BSIs. Materials and Methods: We retrospectively analyzed patients admitted to Cannes hospital between 2021 and 2022 for BSIs due to Enterobacterales. Patient demographics, comorbidities, and main clinical and laboratory parameters during hospitalization were collected. The risk factors for clinical instability after 48 h or death, as well as for ineffective initial empirical therapy, were assessed using univariate and multivariate analyses. Results: From January 2021 to December 2022, 101 subjects were included (mean age 79 years, 60% men, 97% with comorbidities, 17% with healthcare-associated infection, 13% with septic shock, 82% with qPitt severity score < 2, 58% with urinary tract infection, and 18% with AE). Septic shock [adjusted odds ratio (OR_adj) = 5.30, 95% confidence interval (CI): 1.47–22.19, p = 0.014] and ineffective initial empirical therapy [OR_adj 5.54, 95% CI: 1.95–17.01, p = 0.002] were independent predictive factors for clinical instability or death. Extended-spectrum beta-lactamases [OR_adj 9.40, 95% CI: 1.70–62.14, p = 0.012], AE group [OR_adj 5.89, 95% CI: 1.70–21.40, p = 0.006], and clinical instability or death [OR_adj 4.71, 95% CI: 1.44–17.08, p = 0.012] were independently associated with ineffective empirical therapy. Conclusions: Infection with AE was associated with treatment failure. Empirical therapy may result in failure if restricted to 3GC. Full article