-
Frontiers in Microbiology 2024has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction...
OBJECTIVE
has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction of multi-drug resistance (MDR) resistance phenotypes of isolates and clinical samples by genotype is helpful for timely antibiotic treatment.
METHODS
In the study, whole genome sequencing (WGS) data of 494 isolates were used to screen key anti-microbial resistance (AMR)-associated genes related to imipenem (IPM), meropenem (MEM), piperacillin/tazobactam (TZP), and levofloxacin (LVFX) resistance in by comparing genes with copy number differences between resistance and sensitive strains. Subsequently, for the direct prediction of the resistance of to four antibiotics by the AMR-associated features screened, we collected 74 positive sputum samples to sequence by metagenomics next-generation sequencing (mNGS), of which 1 sample with low quality was eliminated. Then, we constructed the resistance prediction model.
RESULTS
We identified 93, 88, 80, 140 AMR-associated features for IPM, MEM, TZP, and LVFX resistance in . The relative abundance of AMR-associated genes was obtained by matching mNGS and WGS data. The top 20 features with importance degree for IPM, MEM, TZP, and LVFX resistance were used to model, respectively. Then, we used the random forest algorithm to construct resistance prediction models of , in which the areas under the curves of the IPM, MEM, TZP, and LVFX resistance prediction models were all greater than 0.8, suggesting these resistance prediction models had good performance.
CONCLUSION
In summary, mNGS can predict the resistance of by directly detecting AMR-associated genes, which provides a reference for rapid clinical detection of drug resistance of pathogenic bacteria.
PubMed: 38903781
DOI: 10.3389/fmicb.2024.1413434 -
Health Science Reports Jun 2024as an opportunistic pathogen produces several virulence factors. This study evaluated the relative frequency of exoenzymes () A, U and S genes and integron classes (I,...
BACKGROUND
as an opportunistic pathogen produces several virulence factors. This study evaluated the relative frequency of exoenzymes () A, U and S genes and integron classes (I, II, and III) among multi-drug-resistant clinical isolates from burn patients in Ahvaz, southwest of Iran.
METHODS
In this cross-sectional study isolates were recovered from 355 wound samples. The antimicrobial susceptibility test was done by disk agar diffusion method on Muller-Hinton agar according to the Clinical and Laboratory Standards Institute. MDR isolates were defined if they showed simultaneous resistance to 3 antibiotics. Extensively drug-resistant was defined as nonsusceptibility to at least one agent in all but two or fewer antimicrobial categories. The presence of class I, II, and III integrons and virulence genes was determined using a PCR assay on extracted DNA.
RESULTS
Overall, 145 clinical isolates were confirmed with biochemical and PCR tests. Overall, 35% (52/145) of the isolates were taken from males and 64% (93/145) from female hospitalized burn patients. The highest resistance rates of isolates to antibiotics were related to piperacillin 59% ( = 86/145) and piperacillin-tazobactam 57% ( = 83/145). A total of 100% of isolates were resistant to at least one antibiotic. MDR and XDR had a frequency of 60% and 29%, respectively. The prevalence of integron classes I, II, and III in was 60%, 7.58%, and 3.44%, respectively. was more common in MDR and XDR isolates. In addition, 70(48%) of isolates did not harbor integron genes. Besides, , and in had a frequency of 55%, 55%, and 56%, respectively.
CONCLUSION
It was found that as a potent pathogen with strong virulence factors and high antibiotic resistance in the health community can cause refractory diseases in burn patients.
PubMed: 38903659
DOI: 10.1002/hsr2.2164 -
Clinical Infectious Diseases : An... Jun 2024The in vitro susceptibility testing interpretive criteria (STIC) for TZP against Enterobacterales were recently updated by the Food and Drug Administration (FDA),...
Piperacillin/tazobactam Susceptibility Test Interpretive Criteria for Enterobacterales: Recommendations from the United States Committee on Antimicrobial Susceptibility Testing.
The in vitro susceptibility testing interpretive criteria (STIC) for TZP against Enterobacterales were recently updated by the Food and Drug Administration (FDA), Clinical & Laboratory Standards Institute (CLSI), and European Committee on Antimicrobial Susceptibility Testing (EUCAST). The United States Committee on Antimicrobial Susceptibility Testing (USCAST) also recently reviewed TZP STIC for Enterobacterales and arrived at different STIC for Enterobacterales and herein we explain our recommendations and rationale behind them. Based on our review of the available data, USCAST does not recommend TZP STIC for certain Enterobacterales species that have a moderate to high likelihood of clinically significant AmpC production (E. cloacae, C. freundii, and K. aerogenes only) or for third-generation cephalosporin-non-susceptible (3GC-NS) Enterobacterales. USCAST recommends a TZP susceptibility breakpoint of ≤ 16/4 mg/L for third-generation cephalosporin-susceptible (3GC-S) Enterobacterales but only endorses the use of extended infusion TZP regimens for patients with infections due to these pathogens.
PubMed: 38902929
DOI: 10.1093/cid/ciae328 -
Enfermedades Infecciosas Y... Jun 2024This study aimed to present real-life data on the use, efficacy, and safety of administering antibiotic therapy through portable elastomeric pumps (pEP) in the...
Outpatient parenteral antibiotic therapy (OPAT) through elastomeric continuous infusion pumps in a real-life observational study: Characteristics, safety, and efficacy analysis.
INTRODUCTION
This study aimed to present real-life data on the use, efficacy, and safety of administering antibiotic therapy through portable elastomeric pumps (pEP) in the outpatient setting.
METHODS
This retrospective observational cohort study was conducted from January 2020 to May 2023 in a large academic hospital in Rome, Italy. All patients receiving antibiotic therapy via pEP were included up to a follow-up period of 90 days after the end of antibiotic therapy. The primary outcome was the treatment response. Secondary endpoints were adverse events attributable to the drug administered, the vascular catheter, or the infection itself.
RESULTS
Of the 490 patients referred to our outpatient parenteral antibiotic therapy (OPAT) unit, 94 (19.2%) received antibiotic therapy via pEP and were included in the final analysis. The most frequently treated infections were those involving bone and prosthetics, including spondylodiscitis (n=27; 28.8%). Most infections were due to Pseudomonas aeruginosa (n=55; 48.3%). Cefepime (n=32; 34.0%), piperacillin/tazobactam (n=29; 30.9%), ceftolozane/tazobactam (n=7; 7.5%), and oxacillin (n=7; 7.5%) were the most frequently administered antibiotics. The infection cure rate reached 88.3% (n=83). 12 patients (12.8%) reported adverse events, of which half (6.4%) were drug-related and half (6.4%) were line-related.
CONCLUSIONS
OPAT through portable elastomeric infusion pumps proved to be safe and effective. It also contributed to the reduction of healthcare costs, fully respecting the principles of personalized medicine. This strategy has emerged as a promising tool for antibiotic stewardship and infection control.
PubMed: 38902156
DOI: 10.1016/j.eimce.2024.04.007 -
The Pediatric Infectious Disease Journal Jun 2024In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping...
BACKGROUND
In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unknown.
METHODS
This retrospective cohort study of simulated antibiotic exposures used published population pharmacokinetic models within drug-specific neonatal intensive care unit cohorts of preterm and term infants, postnatal age 7-60 days and exposed to cefepime, piperacillin-tazobactam or tobramycin. Monte Carlo simulations (NONMEM 7.3) were used to predict steady-state exposures after a 72-hour antibiotic course per Neofax dosing. Exposure was assessed relative to drug-specific minimum inhibitory concentration (MIC) targets between 1 and 16 mcg/mL for Pseudomonas and Enterobacteriaceae species. Postdiscontinuation antibiotic exposure (PDAE) was defined as the time from the last dose to when antibiotic concentration decreased below a specific MIC.
RESULTS
Piperacillin-tazobactam, cefepime and tobramycin cohorts included infants with median gestation age 29, 32 and 32 weeks and postnatal age 17, 19 and 15 days, respectively. The mean PDAE was 19-68 hours, depending on the specific antibiotic/MIC combination. PDAE was longer for infants <28 days old and preterm (vs. term) infants. Cefepime exhibited the longest mean PDAE of 68 hours for Enterobacteriaceae MIC 1. Piperacillin mean PDAE was 25 hours for Enterobacteriaceae MIC 8. Tobramycin had a short mean PDAE of 19 hours.
CONCLUSIONS
Piperacillin and cefepime exposures remained therapeutic long after the expected 8- to 12-hour dosing interval. PDAE is an important consideration for antibiotic stewardship among hospitalized infants, particularly premature infants and those within 1 month postbirth.
PubMed: 38900075
DOI: 10.1097/INF.0000000000004426 -
Health Science Reports Jun 2024Multidrug and extensive drug-resistant was extracted from burn patients referring to burn centers in southwest Iran so that biofilm generation and antibiotic resistance...
BACKGROUND AND AIMS
Multidrug and extensive drug-resistant was extracted from burn patients referring to burn centers in southwest Iran so that biofilm generation and antibiotic resistance could be investigated.
METHODS
A specific primer was used to confirm all our considered 110 culture-positive reports on 345 burn patients. The resistance of to seven antibiotics and Colistin with minimum inhibitory concentration (MIC) was assessed. Biofilm formation was assessed by the phenotypic study of specimens under Congo red agar and microtiter plate assays.
RESULTS
One hundred and 10 clinical isolates taken from burn wound infections were validated. Among isolates, Piperacillin, Ceftazidime, Maeropenem, Gentamycin, and Gatifloacin had the highest resistance to antibiotics, while Ticarcillin-Clavulanic acid and Ceftolozane-Tazobactam showed the least resistance. MICs were then evaluated via the E test. Seven isolates were resistant to colistin. Colistin reference MICs for multidrug-resistant prevalence was 38%, while it was 22% for extensively drug-resistant (XDR) . One was pandrug-resistant (PDR). Under Congo red agar test, 66 isolates (67%) formed biofilms and black colonies, whereas 44 isolates (50%) had red colonies. In MTP, 76% formed biofilm. 40%, 32%, 21% of the isolates were strong, moderate, and weak biofilm formers, respectively, while 43% did not form biofilms.
CONCLUSION
The resistance to antimicrobial agents has largely challenged the control of the infection. Accordingly, a higher resistance occurred when the isolates were transferred to the patients. Less than 50% samples generated strong biofilms. Consequently, hygienic measurements are essential to inhibit transmission to hospitalized patients.
PubMed: 38899004
DOI: 10.1002/hsr2.2138 -
Annals of Clinical Microbiology and... Jun 2024Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat...
BACKGROUND
Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat pathogens due to both intrinsic resistance and the possibility of acquired antimicrobial resistance. Species identification remains challenging leading to imprecise descriptions of resistance in each taxon. Cefiderocol is a broad-spectrum siderophore cephalosporin increasingly used in the management of Achromobacter infections for which susceptibility data remain scarce. We aimed to describe the susceptibility to cefiderocol of a collection of Achromobacter strains encompassing different species and isolation sources from CF or non-CF (NCF) patients.
METHODS
We studied 230 Achromobacter strains (67 from CF, 163 from NCF patients) identified by nrdA gene-based analysis, with available susceptibility data for piperacillin-tazobactam, meropenem and trimethoprim-sulfamethoxazole. Minimal inhibitory concentrations (MICs) of cefiderocol were determined using the broth microdilution reference method according to EUCAST guidelines.
RESULTS
Strains belonged to 15 species. A. xylosoxidans represented the main species (71.3%). MICs ranged from ≤ 0.015 to 16 mg/L with MIC of ≤ 0.015/0.5 mg/L overall and 0.125/2 mg/L against 27 (11.7%) meropenem-non-susceptible strains. Cefiderocol MICs were not related to CF/NCF origin or species although A. xylosoxidans MICs were statistically lower than those of other species considered as a whole. Considering the EUCAST non-species related breakpoint (2 mg/L), 228 strains (99.1%) were susceptible to cefiderocol. The two cefiderocol-resistant strains (A. xylosoxidans from CF patients) represented 3.7% of meropenem-non-susceptible strains and 12.5% of MDR strains.
CONCLUSIONS
Cefiderocol exhibited excellent in vitro activity against a large collection of accurately identified Achromobacter strains, irrespective of species and origin.
Topics: Microbial Sensitivity Tests; Humans; Achromobacter; Anti-Bacterial Agents; Cephalosporins; Cefiderocol; Cystic Fibrosis; Gram-Negative Bacterial Infections
PubMed: 38886694
DOI: 10.1186/s12941-024-00709-z -
Medicine Jun 2024Infective endophthalmitis is an ophthalmic infection that in severe cases can cause complete loss of vision. In children, the defense against infection is low and eye... (Observational Study)
Observational Study
Infective endophthalmitis is an ophthalmic infection that in severe cases can cause complete loss of vision. In children, the defense against infection is low and eye tissue is not fully developed, leading to increased vulnerability to endophthalmitis. Children may be unable to understand the symptoms; thus, developing a method for prevention and treatment of this disease in children is important. Therefore, we analyzed the clinical and pathogenic characteristics of infectious endophthalmitis in children and provided evidence for clinical treatment. The clinical data of 78 children (78 eyes) with infectious endophthalmitis were retrospectively analyzed. The clinical characteristics, pathogen distribution, drug sensitivity, clinical medication, and treatments were summarized and analyzed. In total, 74 (94.87%) had ocular infections caused by trauma and 75 (96.15%) were from rural townships. A total of 108 sterile specimens were examined, with a positive detection rate of 37.04%. The sensitivity rates of Gram-positive cocci and bacilli to vancomycin were 100%. The sensitivity rates of Gram-negative bacilli to ceftazidime, piperacillin/tazobactam, amikacin, gentamicin, ciprofloxacin, and levofloxacin were 100%. Of the 78 patients, 53 (67.95%) received intravitreal injection and 54 (69.23%) underwent vitrectomy. Trauma is the main factor leading to infectious endophthalmitis in children, wherein Gram-positive bacteria are the most common pathogens. Thus, a timely understanding of the pathogen and drug sensitivity is needed. Intravitreal injection and vitrectomy are effective treatments.
Topics: Humans; Endophthalmitis; Retrospective Studies; Child; Male; Female; Child, Preschool; Anti-Bacterial Agents; Infant; Eye Infections, Bacterial; Adolescent; Microbial Sensitivity Tests; Vitrectomy; Intravitreal Injections
PubMed: 38875407
DOI: 10.1097/MD.0000000000038456 -
Urolithiasis Jun 2024Urinary infectious stones are challenging due to bacterial involvement, necessitating a comprehensive understanding of these conditions. Antibiotic-resistant...
Urinary infectious stones are challenging due to bacterial involvement, necessitating a comprehensive understanding of these conditions. Antibiotic-resistant urease-producing bacteria further complicate clinical management. In this study, analysis of urine and stone samples from urinary tract infection (UTI) patients revealed microbial shifts, gene enrichment in stones, and metabolic pathway disparities; antibiotic resistance gene trends were phylum-specific, urease-producing bacteria are at risk of acquiring AMR carried by Enterobacteriaceae under antibiotic, emphasizing potential AMR dissemination between them; Correlations of key pathogenic species in kidney stone and urine microbial communities highlight the need for targeted therapeutic strategies to manage complexities in UTIs; Stones and urine contain a variety of deleterious genes even before antibiotic use, and piperacillin/tazobactam better reduced the abundance of antibiotic resistance genes in stones and urine. The presence of diverse antibiotic resistance and virulence genes underscores challenges in clinical management and emphasizes the need for effective treatment strategies to mitigate risks associated with UTIs and urinary infectious stone formation. Ongoing research is vital for advancing knowledge and developing innovative approaches to address these urological conditions.
Topics: Urinary Tract Infections; Humans; Virulence Factors; Anti-Bacterial Agents; Microbiota; Drug Resistance, Bacterial; Urinary Calculi; Female; Male; Drug Resistance, Microbial
PubMed: 38874649
DOI: 10.1007/s00240-024-01588-x -
Journal of Pharmaceutical and... Jun 2024The investigation of drug disposition in tissues is critical to improving dosing strategy and maximizing treatment effectiveness, yet developing a multi-tissue...
BACKGROUND
The investigation of drug disposition in tissues is critical to improving dosing strategy and maximizing treatment effectiveness, yet developing a multi-tissue bioanalytical method could be challenging due to the differences among various matrices. Herein, we developed an LC-MS/MS method tailored for the quantitation of piperacillin (PIP), cefazolin (CFZ), and cefoxitin (CFX) in rat plasma and 12 tissues, accompanied by validation data for each matrix according to the FDA and EMA guidelines.
RESULTS
The method required only a small sample volume (5 μL plasma or 50-100 μL tissue homogenates) and a relatively simple protocol for simultaneous quantitation of PIP, CFZ, and CFX within different biological matrices. Mobile phase A was composed of 5 mM ammonium formate and 0.1 % formic acid in water, while mobile phase B contained 0.1 % formic acid in acetonitrile. The mobile phase was pumped through a Synergi Fusion-RP column equipped with a guard column with a gradient elution program at a 0.3 mL/min flow rate. The mass spectrometer was operated in positive ionization mode (ESI+) using multiple reaction monitoring.
SIGNIFICANCE
The validated method has been successfully applied to quantify PIP, CFZ, and CFX from the plasma and tissue samples collected in a pilot rat study and will further be used in a large pharmacokinetic study. To our knowledge, this is also the first report presenting long-term, freeze-thaw, and autosampler stability data for PIP, CFZ, and CFX in rat plasma and multiple tissues.
PubMed: 38870837
DOI: 10.1016/j.jpba.2024.116259