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Journal of Global Antimicrobial... Jun 2024Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a...
OBJECTIVES
Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a premature infant and reveals its colistin resistance and evolutionary mechanisms within the host.
METHODS
Three KPC-producing CRKp strains were isolated from a patient with sepsis and CRKp osteoarthritis who had been receiving colistin antimicrobial therapy. The minimum inhibitory concentrations (MICs) of Ceftazidime,Ceftazidime-Avibactam(CAZ-AVI),Meropenem,Imipenem,Tigecycline,Amikacin,Minocycline,Sulfamethoxazole/Trimethoprim,Ciprofloxacin,Levofloxacin,Aztreonam,Cefepime,Cefoperazone/Sulbactam,Piperacillin/Tazobactam and colistin were determined using the microbroth dilution method.The whole-genome sequencing analysis was conducted to determine the STs, virulence genes, and antibiotic resistance genes of three CRKp strains.
RESULTS
Whole-genome sequencing revealed that all three CRKp strains belonged to the sequence type (ST) 11 clone and carried a plasmid encoding blaKPC-2. The three strains all possessed the iucABCDiutA virulence cluster, peg-344 gene, and rmpA/rmpA2 genes, defining them as hv-CRKp. Further experiments and whole-genome analysis revealed that a strain of Kp has developed resistance to colistin. The mechanism found to be responsible for the colistin resistance was a deletion mutation of approximately 9000 bp including mgrB gene.
CONCLUSION
This study characterizes the colistin resistance of ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.
PubMed: 38849114
DOI: 10.1016/j.jgar.2024.05.021 -
JAC-antimicrobial Resistance Jun 2024To analyse the susceptibility profile to cefepime, carbapenems and new β-lactam/β-lactamase inhibitor combinations in complex and isolated from intra-abdominal,...
OBJECTIVES
To analyse the susceptibility profile to cefepime, carbapenems and new β-lactam/β-lactamase inhibitor combinations in complex and isolated from intra-abdominal, urinary, respiratory and bloodstream infections in the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain.
METHODS
The susceptibilities of 759 isolates (473 complex and 286 ) collected in 11 Spanish hospitals from 2016 to 2022 were analysed following the EUCAST 2023 criteria. Molecular characterization looking for β-lactamase genes was performed through PCR and DNA sequencing analysis.
RESULTS
complex showed resistance to third-generation cephalosporins in 25% of the cases, whereas was resistant in 35%. Regarding cefepime, resistance in was higher (10%) than in (2%). Carbapenems showed >85% activity in both microorganisms. Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam had good activity against these microorganisms (>95%). In contrast, the activity of ceftolozane/tazobactam was lower (80%). A high proportion of the isolates resistant to new β-lactam/β-lactamase inhibitor combinations carried a carbapenemase, mainly OXA-48-like and VIM-1.
CONCLUSIONS
Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam show high activity against both complex and isolates recovered in the SMART-Spain study. In contrast, differences have been found in the case of cefepime, showing more activity against than complex. These results are useful for antimicrobial stewardship programmes and for the implementation of local and national guidelines.
PubMed: 38847006
DOI: 10.1093/jacamr/dlae087 -
PLoS Pathogens Jun 2024Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the...
Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the family Enterobacterales. Here we show that two gene cassettes located side-by-side in and ancestral integron similar to In37 have been "harvested" by insertion sequence IS26 as a transposon that is widely disseminated among the Enterobacterales. This transposon encodes the enzymes AAC(6')-Ib-cr and OXA-1, reported, respectively, as amikacin and piperacillin/tazobactam resistance mechanisms. However, by studying bloodstream infection isolates from 769 patients from three hospitals serving a population of 1.2 million people in South West England, we show that increased enzyme production due to mutation in an IS26/In37-derived hybrid promoter or, more commonly, increased transposon copy number is required to simultaneously remove these two key therapeutic options; in many cases leaving only the last-resort antibiotic, meropenem. These findings may help improve the accuracy of predicting piperacillin/tazobactam treatment failure, allowing stratification of patients to receive meropenem or piperacillin/tazobactam, which may improve outcome and slow the emergence of meropenem resistance.
Topics: Humans; Anti-Bacterial Agents; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Piperacillin; Amikacin; Microbial Sensitivity Tests; Enterobacteriaceae Infections; Enterobacteriaceae; Integrons; Bacteremia
PubMed: 38843111
DOI: 10.1371/journal.ppat.1012235 -
Infection and Drug Resistance 2024In this paper, we analyzed the clinical data of patients with meningoencephalitis caused by to understand better the clinical characteristics of the disease and...
OBJECTIVE
In this paper, we analyzed the clinical data of patients with meningoencephalitis caused by to understand better the clinical characteristics of the disease and recommend auxiliary diagnostic mode as well as treatment experience.
METHODS
We reviewed the clinical data of two patients admitted to our department in 2019 with meningoencephalitis caused by .
RESULTS
Two female patients were examined, one of whom had a history of radiotherapy for nasopharyngeal carcinoma while the other had no underlying disease. These two patients were admitted with symptoms of meningoencephalitis. Cerebrospinal fluid examinations revealed elevated levels of leukocytes and protein. After treatment with meropenem, the condition improved for a brief time, but then worsened with a decline in mental status and limb movement. Blood and cerebrospinal fluid cultures demonstrated the absence of pathogenic bacteria, while genome sequencing of cerebrospinal fluids revealed the presence of . Cranial magnetic resonance imaging revealed multiple cerebral abscesses (CAs). After coadministration of linezolid as an anti-infective, clinical symptoms gradually improved, and the CAs shrank on follow-up imaging. The condition exhibited a pattern of improvement-deterioration-improvement.
CONCLUSION
Meningoencephalitis caused by is complex and prone to fluctuation and formation of multiple CAs. The definitive clinical diagnosis of this disease can be aided by genome sequencing technology, and early clarification of the etiology combined with the use of potent antibiotics is effective.
PubMed: 38835493
DOI: 10.2147/IDR.S438615 -
Cureus May 2024A 47-year-old male, a known case of alcoholic chronic liver disease with portal hypertension, presented with complaints of abdominal distension and shortness of breath....
Iatrogenically Acquired Mycobacterium abscessus Infection in an Indwelling Intercostal Drainage In Situ in a Patient With Alcoholic Liver Disease and Bilateral Hepatic Hydrothorax: A Report of a Rare Case.
A 47-year-old male, a known case of alcoholic chronic liver disease with portal hypertension, presented with complaints of abdominal distension and shortness of breath. A provisional diagnosis of ethanol-related compensated chronic liver disease (CLD) with portal hypertension and splenomegaly, gross ascites with bilateral hepatic hydrothorax was made. The left-sided pleural effusion subsided after three pleural taps, but the right-sided effusion kept refilling even after four to five days of repeated therapeutic taps, so a pigtail catheter was left in situ. The pleural fluid was sent for culture which did not grow any pathogenic organisms. Cartridge-based nucleic acid amplification tests where complex (MTBC) was not detected, Ziehl-Neelsen staining was done in which acid-fast bacilli were not seen, and cytology was done where no malignant cells were seen. The patient was discharged with the pigtail in situ on the right side and, after 20 days, the patient again presented with shortness of breath, and imaging revealed moderate right-side pleural effusion. Draining of pleural fluid was done and sent for investigation which again revealed no infective etiology. The patient was admitted to the hospital for one month as the right-sided effusion did not resolve. Suddenly, the patient developed shortness of breath, and a chest X-ray was done, which showed pigtail blockage; pigtail flushing was done, and the bag was drained. The patient was empirically started on IV meropenem 500 mg TID, IV teicoplanin 400 mg BD, and inj polymyxin B 500,000 IU IV BD. The pleural fluid was sent continuously for investigation for the first two months which again did not reveal any infective etiology. After two months of pigtail in situ, the pleural fluid was sent for CBNAAT where MTBC was not detected, and ZN stain showed smooth acid-fast bacilli. The sample was cultured, and it grew acid-fast bacilli in 72 hours on blood agar, MacConkey agar, and Lowenstein-Jensen media. A line probe assay done from the isolate revealed it to be subsp. abscessus which was resistant to macrolides and sensitive to aminoglycosides. subsp. abscessus was isolated from repeated cultures of pleural fluid, and the patient was advised on a combination treatment of amikacin, tigecycline, and imipenem. The patient was discharged with the indwelling pigtail with the advised treatment; unfortunately, we lost patient follow-up as the patient never returned to us.
PubMed: 38832176
DOI: 10.7759/cureus.59626 -
Pakistan Journal of Medical Sciences 2024Our objective was to quantify the number of various bacteria that frequently cause UTI in diabetes patients as well as to gauge their susceptibility and resistance to...
OBJECTIVE
Our objective was to quantify the number of various bacteria that frequently cause UTI in diabetes patients as well as to gauge their susceptibility and resistance to antibiotics.
METHOD
A cross-sectional study was conducted at the Internal Medicine Ward of Lady Reading Hospital, Peshawar, Pakistan from June 2021 to December 2021, Patients with confirmed diabetes were included in the study; however, participants receiving antimicrobial medications for a maximum of 14 days were excluded from the study. Resistance of was asssessed using ciprofloxac, ceftazidime and meropenem.
RESULTS
The findings highlighted the the prevalence of in 38.8% of patients, Candida in 19% of patients, in 11.8% of patients, Pseudomonas in 10%, Klebsiella in 9.5% patients, 6.2% patients and Staphylococcus was found in 5.2% patients. According to the overall sensitivity and resistance of antibiotics in microorganisms, Meropenem showed 89.6% sensitivity and 10.4% resistance. Ciprofloxacin showed 38.9% sensitivity and 61.1% resistance and ceftazidime showed 22.7 sensitivity and 77.3% resistance.
CONCLUSION
UTIs were very common in diabetes patients, and was the most common uropathogen found. Compared to male patients, more female patients had infections. The uropathogens showed a significant degree of resistance to ceftizidime and ciprofloxacin.
PubMed: 38827869
DOI: 10.12669/pjms.40.5.8275 -
Frontiers in Cellular and Infection... 2024The increasing incidence of Klebsiella pneumoniae and carbapenem-resistant Klebsiella pneumoniae (CRKP) has posed great challenges for the clinical anti-infective...
INTRODUCTION
The increasing incidence of Klebsiella pneumoniae and carbapenem-resistant Klebsiella pneumoniae (CRKP) has posed great challenges for the clinical anti-infective treatment. Here, we describe the molecular epidemiology and antimicrobial resistance profiles of K. pneumoniae and CRKP isolates from hospitalized patients in different regions of China.
METHODS
A total of 219 K. pneumoniae isolates from 26 hospitals in 19 provinces of China were collected during 2019-2020. Antimicrobial susceptibility tests, multilocus sequence typing were performed, antimicrobial resistance genes were detected by polymerase chain reaction (PCR). Antimicrobial resistance profiles were compared between different groups.
RESULTS
The resistance rates of K. pneumoniae isolates to imipenem, meropenem, and ertapenem were 20.1%, 20.1%, and 22.4%, respectively. A total of 45 CRKP isolates were identified. There was a significant difference in antimicrobial resistance between 45 CRKP and 174 carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains, and the CRKP isolates were characterized by the multiple-drug resistance phenotype.There were regional differences among antimicrobial resistance rates of K. pneumoniae to cefazolin, chloramphenicol, and sulfamethoxazole,which were lower in the northwest than those in north and south of China.The mostcommon sequence type (ST) was ST11 (66.7% of the strains). In addition, we detected 13 other STs. There were differences between ST11 and non-ST11 isolates in the resistance rate to amikacin, gentamicin, latamoxef, ciprofloxacin, levofloxacin, aztreonam, nitrofurantoin, fosfomycin, and ceftazidime/avibactam. In terms of molecular resistance mechanisms, the majority of the CRKP strains (71.1%, 32/45) harbored blaKPC-2, followed by blaNDM (22.2%, 10/45). Strains harboring blaKPC or blaNDM genes showed different sensitivities to some antibiotics.
CONCLUSION
Our analysis emphasizes the importance of surveilling carbapenem-resistant determinants and analyzing their molecular characteristics for better management of antimicrobial agents in clinical use.
Topics: Klebsiella pneumoniae; Humans; China; Klebsiella Infections; Microbial Sensitivity Tests; Anti-Bacterial Agents; Molecular Epidemiology; Multilocus Sequence Typing; Drug Resistance, Multiple, Bacterial; Male; Carbapenem-Resistant Enterobacteriaceae; Female; Middle Aged; Aged; Hospitalization; Adult; Carbapenems
PubMed: 38817445
DOI: 10.3389/fcimb.2024.1380678 -
Scientific Reports May 2024Contaminated lake water and fish can be sources of bacterial pathogens of public health concern, including pathogenic E. coli. Within Ethiopia, specifically, Central...
Occurrence, molecular characterization, and antimicrobial susceptibility of sorbitol non-fermenting Escherichia coli in lake water, fish and humans in central Oromia, Ethiopia.
Contaminated lake water and fish can be sources of bacterial pathogens of public health concern, including pathogenic E. coli. Within Ethiopia, specifically, Central Oromia, raw fish consumption is a common practice. Although there are few reports on occurrence of E. coli O157 in fish destined for human consumption and children under five years, information on the transmission pathways of E. coli O157 and other sorbitol non-fermenting (SN-F) E. coli from water-to-fish-to-human, and their virulence factors and antimicrobial resistant determinants along the fish supply chain is lacking. The study aimed to investigate the occurrence, molecular characteristics, and antimicrobial susceptibility of E. coli O157 and other SN-F E. coli strains in fish, lake water and humans in central Oromia, Ethiopia. A total of 750 samples (450 fish samples, 150 water samples, 150 human stool samples) were collected from five lakes and three health facilities. The samples were processed following the standard protocol recommended by European Food Safety Authority and Kirby-Bauer disc diffusion method for detection of the bacteria, and antimicrobial susceptibility tests, respectively. Molecular characterization of presumptive isolates was performed using Whole-Genome Sequencing (WGS) for serotyping, determination of virulence factors, antimicrobial resistance traits, and genetic linkage of the isolates. Overall, 3.9% (29/750) of the samples had SN-F E. coli; of which 6.7% (n = 10), 1.8% (n = 8) and 7.3% (n = 11) were retrieved from water, fish, and diarrheic human patients, respectively. The WGS confirmed that all the isolates were SN-F non-O157: H7 E. coli strains. We reported two new E. coli strains with unknown O-antigen from fish and human samples. All the strains have multiple virulence factors and one or more genes encoding for them. Genetic relatedness was observed among strains from the same sources (water, fish, and humans). Most isolates were resistant to ampicillin (100%), tetracycline (100%), cefotaxime (100%), ceftazidime (100%), meropenem (100%), nalidixic acid (93.1%) and sulfamethoxazole/trimethoprim (79.3%). Majority of the strains were resistant to chloramphenicol (58.6%) and ciprofloxacin (48.3%), while small fraction showed resistance to azithromycin (3.45%). Isolates had an overall MDR profile of 87.5%. Majority, (62.1%; n = 18) of the strains had acquired MDR traits. Genes encoding for mutational resistance and Extended-spectrum beta-lactamases (ESBL) were also detected. In conclusion, our study revealed the occurrence of virulent and MDR SN-F E. coli strains in water, fish, and humans. Although no genetic relatedness was observed among strains from various sources, the genomic clustering among strains from the same sources strongly suggests the potential risk of transmission along the supply chain at the human-fish-environment interface if strict hygienic fish production is not in place. Further robust genetic study of the new strains with unknown O-antigens, and the epidemiology of SN-F E. coli is required to elucidate the molecular profile and public health implications of the pathogens.
Topics: Humans; Ethiopia; Animals; Lakes; Sorbitol; Fishes; Escherichia coli; Microbial Sensitivity Tests; Escherichia coli Infections; Anti-Bacterial Agents; Virulence Factors; Whole Genome Sequencing; Water Microbiology; Drug Resistance, Bacterial; Food Microbiology; Feces; Escherichia coli O157
PubMed: 38816376
DOI: 10.1038/s41598-024-61810-z -
Open Forum Infectious Diseases May 2024discordance in β-lactams' activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance is...
BACKGROUND
discordance in β-lactams' activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance is attributed to the supra-physiologic zinc concentration in testing media.
METHODS
A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing was performed. Outcomes of patients treated empirically with non-MBL-active β-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active β-lactam therapy (ceftazidime/avibactam + aztreonam) were documented. The patients' isolates were used to induce septicemia in mice, and survival upon meropenem treatment was recorded. Meropenem minimum inhibitory concentrations (MICs) were determined in standard media and in the presence of physiological zinc concentrations.
RESULTS
Twenty-nine patients receiving empiric non-MBL-active β-lactams (median duration, 4 days) were compared with 29 receiving MBL-active β-lactams. The 14-day mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality ( < .0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower vs MICs in zinc-unadjusted broth (≥64 mg/L).
CONCLUSIONS
Our data provide foundational support to establish pharmacokinetic/pharmacodynamic relationships using MICs derived in physiologic zinc concentration, which may better predict β-lactam therapy outcome.
PubMed: 38813259
DOI: 10.1093/ofid/ofae228 -
IJID Regions Jun 2024Evidence-based prescribing is essential to optimize patient outcomes in cystitis. This requires knowledge of local antibiotic resistance rates. Diagnostic and...
Regional variations in antimicrobial susceptibility of community-acquired uropathogenic in India: Findings of a multicentric study highlighting the importance of local antibiograms.
OBJECTIVES
Evidence-based prescribing is essential to optimize patient outcomes in cystitis. This requires knowledge of local antibiotic resistance rates. Diagnostic and Antimicrobial Stewardship (DASH) to Protect Antibiotics (https://dashuti.com/) is a multicentric mentorship program guiding centers in preparing, analyzing and disseminating local antibiograms to promote antimicrobial stewardship in community urinary tract infection. Here, we mapped the susceptibility profile of from 22 Indian centers.
METHODS
These centers spanned 10 Indian states and three union territories. Antibiograms for urinary from the outpatient departments were collated. Standardization was achieved by regional online training; anomalies were resolved via consultation with study experts. Data were collated and analyzed.
RESULTS
Nationally, fosfomycin, with 94% susceptibility (inter-center range 83-97%), and nitrofurantoin, with 85% susceptibility (61-97%), retained the widest activity. The susceptibility rates were lower for co-trimoxazole (49%), fluoroquinolones (31%), and oral cephalosporins (26%). The rates for third- and fourth-generation cephalosporins were 46% and 52%, respectively, with 54% (33-58%) extended-spectrum β-lactamase prevalence. Piperacillin-tazobactam (81%), amikacin (88%), and meropenem (88%) retained better activity; however, one center in Delhi recorded only 42% meropenem susceptibility. Susceptibility rates were mostly higher in South, West, and Northeast India; centers in the heavily populated Gangetic plains, across north and northwest India, had greater resistance. These findings highlight the importance of local antibiograms in guiding appropriate antimicrobial choices.
CONCLUSIONS
Fosfomycin and nitrofurantoin are the preferred oral empirical choices for uncomplicated cystitis in India, although elevated resistance in some areas is concerning. Empiric use of fluoroquinolones and third-generation cephalosporins is discouraged, whereas piperacillin/tazobactam and aminoglycosides remain carbapenem-sparing parenteral agents.
PubMed: 38812702
DOI: 10.1016/j.ijregi.2024.100370