-
Intensive Care Medicine Aug 2023Inadequate piperacillin (PIP) exposure in intensive care unit (ICU) patients threatens therapeutic success. Model-informed precision dosing (MIPD) might be promising to...
Towards model-informed precision dosing of piperacillin: multicenter systematic external evaluation of pharmacokinetic models in critically ill adults with a focus on Bayesian forecasting.
PURPOSE
Inadequate piperacillin (PIP) exposure in intensive care unit (ICU) patients threatens therapeutic success. Model-informed precision dosing (MIPD) might be promising to individualize dosing; however, the transferability of published models to external populations is uncertain. This study aimed to externally evaluate the available PIP population pharmacokinetic (PopPK) models.
METHODS
A multicenter dataset of 561 ICU patients (11 centers/3654 concentrations) was used for the evaluation of 24 identified models. Model performance was investigated for a priori (A) predictions, i.e., considering dosing records and patient characteristics only, and for Bayesian forecasting, i.e., additionally including the first (B1) or first and second (B2) therapeutic drug monitoring (TDM) samples per patient. Median relative prediction error (MPE) [%] and median absolute relative prediction error (MAPE) [%] were calculated to quantify accuracy and precision.
RESULTS
The evaluation revealed a large inter-model variability (A: MPE - 135.6-78.3% and MAPE 35.7-135.6%). Integration of TDM data improved all model predictions (B1/B2 relative improvement vs. A: |MPE| 45.1/67.5%; MAPE 29/39%). The model by Kim et al. was identified to be most appropriate for the total dataset (A/B1/B2: MPE - 9.8/- 5.9/- 0.9%; MAPE 37/27.3/23.7%), Udy et al. performed best in patients receiving intermittent infusion, and Klastrup et al. best predicted patients receiving continuous infusion. Additional evaluations stratified by sex and renal replacement therapy revealed further promising models.
CONCLUSION
The predictive performance of published PIP models in ICU patients varied considerably, highlighting the relevance of appropriate model selection for MIPD. Our differentiated external evaluation identified specific models suitable for clinical use, especially in combination with TDM.
Topics: Humans; Adult; Piperacillin; Bayes Theorem; Critical Illness; Critical Care; Drug Monitoring; Anti-Bacterial Agents
PubMed: 37439872
DOI: 10.1007/s00134-023-07154-0 -
Medicina (Kaunas, Lithuania) Sep 2023. Numerous studies have been conducted to explore the epidemiological characteristics of urinary tract infections (UTI) and sepsis. However, there is still a lack of...
. Numerous studies have been conducted to explore the epidemiological characteristics of urinary tract infections (UTI) and sepsis. However, there is still a lack of relevant bacteriological features and prognostic information regarding urosepsis based on bacteriological etiology. The current study aims to evaluate the bacterial etiology of complicated UTI (cUTI) and bacterial resistance to antibiotics and whether they present an intrinsic risk of developing urosepsis. . A retrospective study was performed that included 102 patients who were diagnosed with cUTI and admitted to the urology department of the "Sfântul Apostol Andrei" County Emergency Clinical Hospital (GCH) from September 2019 to May 2022. A considerable number of patients, n = 41 (40.2%), were diagnosed with multi drug-resistant (MDR) infection. () was identified as the prevailing pathogen, accounting for 51 patients. manifested itself as the subsequent causative agent in 27 instances. The presence of spp. infection was documented in 13 patients, whereas emerged as the etiological perpetrator in the clinical context of 8 patients. The current study found a substantial prevalence of resistance to first-line antibiotics. The overall resistance rate was 74.5% for penicillin, 58.82% for trimethoprim-sulfamethoxazole and 49% for fluoroquinolones; cephalosporin resistance displayed an inverse correlation with antibiotic generation with fourth-generation cephalosporins exhibiting a resistance rate of 24.5%, and first-generation cephalosporins demonstrating a resistance rate of 35.29%. . Age, comorbidities and indwelling urinary catheters are risk factors for developing MDR infections. While the intrinsic characteristics of the causative bacterial agent in cUTI may not be a risk factor for developing urosepsis, they can contribute to increased mortality risk. For empiric antibiotic treatment in patients with cUTI who are at a high risk of developing urosepsis and experiencing a potentially unfavorable clinical course, broad-spectrum antibiotic therapy is recommended. This may include antibiotics, such as amikacin, tigecycline, carbapenems and piperacillin-tazobactam.
Topics: Humans; Escherichia coli; Retrospective Studies; Anti-Bacterial Agents; Urinary Tract Infections; Bacteria; Bacterial Infections; Cephalosporins
PubMed: 37763805
DOI: 10.3390/medicina59091686 -
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 -
Fukushima Journal of Medical Science Nov 2023The incidence of Acinetobacter infections has increased in recent years. Acinetobacter infections are resistant to most antibiotics and can be found in hospitalized...
The incidence of Acinetobacter infections has increased in recent years. Acinetobacter infections are resistant to most antibiotics and can be found in hospitalized patients. Pregnancies complicated by severe sepsis or septic shock are associated with a higher rate of preterm labor and delivery, fetal infection, and operative delivery. This case report describes septic shock due to Acinetobacter lwoffii infection in the 31st week of gestation. A 47-year-old woman, with a gestation of 31 weeks and one day, presented with a fever, and signs of bacterial infection on laboratory tests. Although the patient was started on tazobactam/piperacillin, she went into septic shock, and was transferred to our hospital. Cesarean section was performed at a gestation of 31 weeks and 4 days because of severe maternal pneumonia and non-reassuring fetal status. A. lwoffii was detected in blood cultures collected at the previous hospital, and susceptibility to piperacillin and meropenem to A. lwoffii was confirmed. The pneumonia responded to antibiotic treatment and there were no findings of infection in the neonate. Maternal sepsis is an infrequent but important complication, causing significant maternal and fetal morbidity and fetal and neonatal mortality; therefore, early antibiotic therapy is required to improve the clinical outcome.
Topics: Infant, Newborn; Humans; Pregnancy; Female; Middle Aged; Shock, Septic; Acinetobacter Infections; Cesarean Section; Anti-Bacterial Agents; Piperacillin; Pneumonia
PubMed: 37766560
DOI: 10.5387/fms.2022-43 -
Antimicrobial Agents and Chemotherapy Sep 2023This study compared the efficacy of flomoxef with other β-lactam antibiotics against extended-spectrum β-lactamases (ESBL)-producing bacteria of clinical relevance....
This study compared the efficacy of flomoxef with other β-lactam antibiotics against extended-spectrum β-lactamases (ESBL)-producing bacteria of clinical relevance. First, the prevalence and β-lactamase genotypes of ESBL-producing strains among and isolates collected in Japan from 2004 to 2018 were investigated. High MIC values (>64 µg/mL) of ceftriaxone, cefepime, and ceftazidime and low MIC values (≤0.06-2 µg/mL) of flomoxef, cefmetazole, and meropenem against both species were observed. Second, a chemostat model was used to analyze the efficacy of humanized regimens of three oxacephem/cephamycin antibiotics (flomoxef, cefmetazole, cefoxitin) and two other antibiotics (meropenem and piperacillin/tazobactam) in suppressing the growth of five ESBL-producing and two strains. Flomoxef, piperacillin/tazobactam, and meropenem showed good bactericidal effects with >4 log CFU/mL reduction without bacterial regrowth at 24 h even when the MIC of test isolates was >MIC. Cefmetazole and cefoxitin resulted in regrowth of test isolates with MIC ≥MIC at 24 h. Cefmetazole, cefoxitin, flomoxef, and meropenem showed increased MICs for regrown samples. A clear relationship between the proportion of time that the free drug concentration exceeded the MIC (%T) and antibiotic efficacy was found for flomoxef, cefoxitin, and cefmetazole, and flomoxef had the highest %T, whereas discrepancies between Clinical and Laboratory Standards Institute breakpoint and bactericidal activity were observed for cefmetazole. Flomoxef was effective in preventing the growth of all ESBL-producing strains, even those with an MIC eight times the MIC. Thus, flomoxef may be a good alternative to meropenem in context of carbapenems sparing stewardship.
Topics: Cefoxitin; Cefmetazole; Klebsiella pneumoniae; Meropenem; Escherichia coli; Anti-Bacterial Agents; Piperacillin; Tazobactam
PubMed: 37610203
DOI: 10.1128/aac.00258-23 -
Infection and Drug Resistance 2023Patients after hematopoietic stem cell transplantation (HSCT) are often followed by bloodstream infections (BSIs). BSI is an important cause of non-relapse mortality...
PURPOSE
Patients after hematopoietic stem cell transplantation (HSCT) are often followed by bloodstream infections (BSIs). BSI is an important cause of non-relapse mortality (NRM) in HSCT patients.
METHODS
We conducted a retrospective cohort study of patients (aged >14 years) who underwent HSCT at our hospital from 2017 to 2021. Population characteristics, BSI microbiology, resistance to common antibiotics, and 30-day all-cause mortality were analyzed.
RESULTS
Of 3054 patients, 169 (5.5%) had BSIs after HSCT. Male, not in complete remission at transplantation and longer duration of neutropenia were risk factors for the development of BSI after HSCT. These BSIs were Gram-negative bacterial (n=123, 69.49%), Gram-positive bacterial (n=27, 15.25%), fungal (n=11, 6.36%), and polymicrobial (n=16, 9.25%). Among the Gram-negative bacteria, the proportions of isolates resistant to ceftazidime, cefepime, and piperacillin-tazobactam were similar (72.93%, 74.80%, and 77.42%, respectively). The overall drug resistance rates of amikacin and imipenem were 16.13% and 43.90%, respectively. isolates were methicillin-resistant. In isolates, the penicillin resistance rate was 84.62%. Eleven isolates of were resistant to fluconazole and were sensitive to amphotericin B and flucytosine. The 30-day all-cause mortality rate of the 169 patients with BSIs was 8.88%. The 30-day all-cause mortality of patients with Gram-negative bacterial BSIs was 7.32%, 25.00% for polymicrobial BSIs, and 36.36% for fungal BSIs. The 30-day all-cause mortality of patients with fungal BSIs was significantly higher than that of patients with Gram-negative (=0.0023) and Gram-positive bacteria (=0.0023). Fungal BSI and non-Hodgkin's lymphoma (NHL) were associated with higher 30-day mortality.
CONCLUSION
Our study reveals the microbiological characteristics and 30-day all-cause mortality in patients with bloodstream infections after HSCT. Our data provides strong support for empirical antimicrobial therapy and infection prevention strategies for patients with BSIs after HSCT.
PubMed: 37609663
DOI: 10.2147/IDR.S420310 -
Diabetes Therapy : Research, Treatment... Jul 2024This study aimed to determine the pathogen distribution and drug susceptibility of diabetic foot wound secretions in a tertiary hospital in a coastal area of...
INTRODUCTION
This study aimed to determine the pathogen distribution and drug susceptibility of diabetic foot wound secretions in a tertiary hospital in a coastal area of southeastern China to guide clinical antibiotic selection.
METHODS
A retrospective analysis was conducted on 212 patients with diabetic foot hospitalized at Xiamen Third Hospital from 2018 to 2023, and foot wound secretions were collected for microbial culture and drug susceptibility testing.
RESULTS
Among 212 cases of patients with diabetic foot wound secretions, 163 cases (76.9%) were cultured with pathogenic bacteria, and a total of 207 strains of pathogenic bacteria were cultured, including 75 strains (36.23%) of Gram-positive (G+) bacteria, 118 strains of Gram-negative (G-) bacteria (57.00%), 14 strains of fungi (6.76%), 120 cases of single microorganism infection (73.62%), 43 cases of mixed infection (26.38%), and 15 strains of multidrug-resistant bacteria (7.25%). The top three pathogenic bacteria were Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. G+ bacteria were dominated by S. aureus. Drug susceptibility results showed that G+ bacteria were highly susceptible to vancomycin, linezolid, tigecycline, quinupristin/dalfopristin, rifampicin, and furotoxin, and somewhat resistant to penicillin, erythromycin, clindamycin, and cefoxitin. Among G- bacterial infections, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Proteus were the major species. Drug susceptibility testing indicated that carbapenems such as imipenem and ertapenem were the most effective antibacterial drugs against G- strains, followed by amikacin, piperacillin, and tazabactams to which these bacteria were also relatively sensitive, while resistance to penicillins and first-generation cephalosporins increased significantly. We isolated one strain of pathogenic bacteria from a Wagner grade 1 ulcer, which was G+ bacteria. In Wagner grade 2 ulcers, the distribution of pathogenic bacteria was mainly G+ bacteria. In Wagner grade 3 and 4 ulcers, the distribution of pathogenic bacteria was mainly G- bacteria, and the increased rate of mixed infection was mainly due to mixed infection of G+ and G-. Two strains of pathogenic bacteria were isolated at Wagner grade 5, which were mixed infections of G+ and G-.
CONCLUSIONS
Pathogenic bacteria in diabetic foot wounds are predominantly G- bacteria, followed by G+ bacteria. As the Wagner ulcer grade increases, the distribution of pathogenic bacteria changes from G+ bacteria to G- bacteria, and the mixed infection rate increases. G+ bacteria are highly susceptible to vancomycin, linezolid, tigecycline, quinupristin/dalfopristin, rifampicin, and furotoxin, and somewhat resistant to penicillin, erythromycin, clindamycin, and cefoxitin. G- bacteria are more sensitive to the antimicrobial drugs ertapenem, imipenem, amikacin, piperacillin tazobactam, and have high resistance to penicillin and first-generation cephalosporins.
PubMed: 38771473
DOI: 10.1007/s13300-024-01601-x -
Cureus Sep 2023Background This study was designed to evaluate the current in vitro susceptibility of clinical isolates to broad-spectrum β-lactam antibiotics. Methodology Bacterial...
In Vitro Susceptibility of Clinical Isolates to Ceftriaxone Alone and Ceftriaxone in Combination With Sulbactam or Tazobactam: A Comparative Study of Broad-Spectrum β-Lactam Antibiotics in India.
Background This study was designed to evaluate the current in vitro susceptibility of clinical isolates to broad-spectrum β-lactam antibiotics. Methodology Bacterial isolates, cultured from 180 non-repetitive clinical samples between April and November 2022 at three hospitals in India, were used to evaluate the minimum inhibitory concentration (MIC) of broad-spectrum β-lactam antibiotics using the Epsilometer test (E-test) method. Test antibiotics were ceftriaxone and ceftriaxone in combination with β-lactamase inhibitors (BLIs) sulbactam and tazobactam. Comparator antibiotics included amoxicillin + BLI clavulanic acid, piperacillin + tazobactam, cefotaxime, and cefepime. The MIC values obtained were used to assess the susceptibility of the isolates and to compute the efficacy ratios (ERs) of the antibiotics. Results Among the 180 clinical isolates, ~89% were gram-negative bacteria, the most prevalent ones being and . Of the gram-negative isolates, ~37% were susceptible/intermediately susceptible to ceftriaxone, and ~29% were susceptible to ceftriaxone + BLIs. The test antibiotics had ER >10 against 85%-95% isolates, whereas comparator antibiotics had ER >10 against 31%-68% isolates. The differences between the test antibiotics and piperacillin + tazobactam or cefotaxime were statistically significant. Ceftriaxone, ceftriaxone + sulbactam, and ceftriaxone + tazobactam had ER >10 against 78%, 100%, and 90% of isolates, while the corresponding percentages for cefotaxime, piperacillin + tazobactam, and cefepime were 100%, 64%, and 80%, respectively. The difference between ceftriaxone + BLIs and piperacillin + tazobactam was statistically significant. Ceftriaxone + BLIs had ER >10 against all isolates producing extended-spectrum β-lactamases (ESBLs); the percentage of isolates was significantly higher than that for piperacillin + tazobactam. Ceftriaxone + tazobactam had ER >10 against all ESBL-producing isolates; ceftriaxone and ceftriaxone + sulbactam had ER ranging 6-10. Conclusions Ceftriaxone and ceftriaxone in combination with sulbactam and tazobactam are promising antibiotics to explore against prevalent infectious microorganisms such as and . Ceftriaxone + tazobactam also holds promise against ESBL-producing variants.
PubMed: 37900428
DOI: 10.7759/cureus.46014 -
Antibiotics (Basel, Switzerland) Nov 2023() is one of the common pathogens found in poultry flocks, resulting in serious economic losses for the poultry industry due to high mortality, reduced growth rate,...
() is one of the common pathogens found in poultry flocks, resulting in serious economic losses for the poultry industry due to high mortality, reduced growth rate, poor feed conversion, increased condemnations, and high treatment costs. The aim of this study was to phenotypically characterize phylogenetic relationships and assess the presence of resistance gene strains of obtained from various poultry species in Poland. A total of 57 isolates of were included in this study. A polymerase chain reaction (PCR) and matrix assisted laser desorption ionization mass spectrometry (MALDI-TOF MS) were used for identification of the strains. The phylogenetic relationship of the isolates was determined by analysing the B gene sequence. The susceptibility to antibiotics was evaluated by minimum inhibitory concentration (MIC) in liquid media. All of the field strains of were grouped into one of two clades resulting from B gene sequencing. High MIC and MIC values were obtained for gentamycin, amikacin, and colistin. Low MIC and MIC values were obtained for amoxicillin cefuroxime, cefoperazone, piperacillin, and trimethoprim/sulfamethoxazole. Among the resistance genes, and were identified most frequently. This is the first phenotypic characterization of strains obtained from poultry flocks in Poland.
PubMed: 38136682
DOI: 10.3390/antibiotics12121648 -
Infection and Drug Resistance 2023Bacterial otitis media (OM) is a common infection among the pediatric community worldwide and is the first reason for prescribing antibiotics in pediatric practices....
BACKGROUND
Bacterial otitis media (OM) is a common infection among the pediatric community worldwide and is the first reason for prescribing antibiotics in pediatric practices. However, if not promptly diagnosed and appropriately treated, it may persist and cause severe intra- and extra-cranial hard-to-cure complications. Hence, knowing the magnitude, etiology, and antibiotic susceptibility profile is very important for the proper management.
METHODS
A cross-sectional study was carried out in 312 pediatrics (1 to 18 years) attending the Ear Nose Throat outpatient departments of the two title hospitals from 25 February to 30th August 2022. Patients were chosen through a systematic random sampling method. Data were obtained by means of a semi-structured questionnaire. Samples were collected to identify the causative bacteria as per microbiological guidelines. The antibiotic susceptibility test was done according to the Kirby-Bauer disc diffusion; SPSS version 25 was used for the analysis.
RESULTS
The overall prevalence of otitis media was 67.3% (n=210); CSOM showed a slight preponderance (n=107) Gram-negative bacteria and Gram-positive bacteria were present in 59.8% (n=137) and 40.1% (n=92), respectively. Otitis media was predominantly caused by (n=52, 56.5%), followed by spp. (n=33, 24%). Gram-negative bacteria were highly resistant to co-trimoxazole, amoxicillin-clavulanic acid, piperacillin, and tetracycline, whereas their positive counterparts were considerably penicillin and co-trimoxazole resistant. Overall, 61.5 and 19.2% of the isolates were MDR and XDR, respectively. MRSA, MR-CoNs, and VRE were 38.4% (n=20), 17.1% (n=5), and 58.3% (n=12), respectively; 19.7% (n=25) of Gram-negative bacteria produced ESBL, and 7% (n=9) were carbapenem-resistant. History of exposure to loud noise [AOR=3.4; CI=1.14-10.23; P-value=0.028] and family history of smoking at home [AOR=2.9; CI=1.18-7.25; P-value=0.020] have the greatest odds of otitis media.
CONCLUSION
Overall, the prevalence of otitis media is showing an upward trend, and MDR among bacterial isolates is increasing alarmingly.
PubMed: 37789841
DOI: 10.2147/IDR.S424927