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JAMA May 2023Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of...
IMPORTANCE
Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood.
OBJECTIVE
To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics.
DESIGN, SETTING, AND PARTICIPANTS
Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment.
INTERVENTION
The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care).
MAIN OUTCOMES AND MEASURES
The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program.
RESULTS
The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32).
CONCLUSIONS AND RELEVANCE
In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03269994.
Topics: Male; Adult; Humans; Aged; Cefoxitin; Piperacillin; Pancreaticoduodenectomy; Pancreatic Fistula; Penicillanic Acid; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection; Sepsis
PubMed: 37078771
DOI: 10.1001/jama.2023.5728 -
The American Journal of Tropical... Oct 2022Snakebite is a common occurrence in Hangzhou, and identifying bacteria in wounds is very important for snakebite treatment. To define the pattern of wound bacterial... (Review)
Review
Snakebite is a common occurrence in Hangzhou, and identifying bacteria in wounds is very important for snakebite treatment. To define the pattern of wound bacterial flora of venomous snakebites and their susceptibility to common antibiotics, we reviewed the medical charts of patients admitted with snakebite at Hangzhou TCM Hospital from January 2019 to December 2020. A total of 311 patients were enrolled in this study. Among them, bacteria culture was positive in 40 patients, and 80 organisms were isolated. The most frequent pathogens were Morganella morganii and Staphylococcus aureus. According to the results of susceptibility testing, a majority of the isolates were resistant to some common first-line antibiotics, such as ampicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, cefoxitin, and cephazolin. Quinolones, however, have shown a better antibacterial effect. In conclusion, snakebite wounds involve a wide range of bacteria. Fluoroquinolones, such as levofloxacin and ciprofloxacin, could be an alternative for empirical treatment in patients with snakebite when the effect of other antibiotics is poor.
Topics: Amoxicillin; Ampicillin; Anti-Bacterial Agents; Bacteria; Cefazolin; Cefoxitin; Ciprofloxacin; Clavulanic Acid; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Snake Bites; Sulbactam; Venoms
PubMed: 36067984
DOI: 10.4269/ajtmh.21-1314 -
Scientific Reports Nov 2022Understanding the response of bacteria to environmental stress is hampered by the relative insensitivity of methods to detect growth. This means studies of antibiotic...
Understanding the response of bacteria to environmental stress is hampered by the relative insensitivity of methods to detect growth. This means studies of antibiotic resistance and other physiological methods often take 24 h or longer. We developed and tested a scattered light and detection system (SLIC) to address this challenge, establishing the limit of detection, and time to positive detection of the growth of small inocula. We compared the light-scattering of bacteria grown in varying high and low nutrient liquid medium and the growth dynamics of two closely related organisms. Scattering data was modelled using Gompertz and Broken Stick equations. Bacteria were also exposed meropenem, gentamicin and cefoxitin at a range of concentrations and light scattering of the liquid culture was captured in real-time. We established the limit of detection for SLIC to be between 10 and 100 cfu mL in a volume of 1-2 mL. Quantitative measurement of the different nutrient effects on bacteria were obtained in less than four hours and it was possible to distinguish differences in the growth dynamics of Klebsiella pneumoniae 1705 possessing the Bla betalactamase vs. strain 1706 very rapidly. There was a dose dependent difference in the speed of action of each antibiotic tested at supra-MIC concentrations. The lethal effect of gentamicin and lytic effect of meropenem, and slow bactericidal effect of cefoxitin were demonstrated in real time. Significantly, strains that were sensitive to antibiotics could be identified in seconds. This research demonstrates the critical importance of improving the sensitivity of bacterial detection. This results in more rapid assessment of susceptibility and the ability to capture a wealth of data on the growth dynamics of bacteria. The rapid rate at which killing occurs at supra-MIC concentrations, an important finding that needs to be incorporated into pharmacokinetic and pharmacodynamic models. Importantly, enhanced sensitivity of bacterial detection opens the possibility of susceptibility results being reportable clinically in a few minutes, as we have demonstrated.
Topics: Anti-Bacterial Agents; Meropenem; Cefoxitin; Klebsiella pneumoniae; Gentamicins; Microbial Sensitivity Tests
PubMed: 36371444
DOI: 10.1038/s41598-022-22671-6 -
Annals of Medicine Dec 2022To determine the minimum inhibitory concentration (MIC) distribution of antibacterial drugs and the susceptibility of non-tuberculous mycobacterial (NTM) isolates to...
Antimicrobial susceptibility and minimum inhibitory concentration distribution of common clinically relevant non-tuberculous mycobacterial isolates from the respiratory tract.
To determine the minimum inhibitory concentration (MIC) distribution of antibacterial drugs and the susceptibility of non-tuberculous mycobacterial (NTM) isolates to provide a reference basis for the clinical selection of an effective starting regimen. The common clinical isolates of NTM in the respiratory tract, which met the standards of the American Thoracic Society for NTM lung disease, were collected. The MICs of 81 isolates were determined using the microbroth dilution method (Thermo Fisher Scientific, USA), as recommended by the Clinical and Laboratory Standards Institute, USA. Included were 43 complex (MAC) strains, 24 complex (MAB) strains, and 14 strains. The sensitivity rates of MAC to clarithromycin and amikacin were 81.4% and 79.1%, respectively, while the sensitivity rates to linezolid and moxifloxacin were only 20.9% and 9.3%; the MIC of rifabutin was the lowest (MIC50% was just 2 μg/mL). After incubation for 3-5 days, the sensitivity rate of MAB to clarithromycin was 87.5%; this decreased to 50% after 14 days' incubation. Most of them were susceptible to amikacin (91.6%), and most were resistant to moxifloxacin (95.8%), ciprofloxacin (95.8%), imipenem (95.8%), amoxicillin/clavulanate (95.8%), tobramycin (79.1%), doxycycline (95.8%) and trimethoprim/sulfamethoxazole (95.8%). intermediate (83.3%) and resistant (16.7%) to cefoxitin. The susceptibility to linezolid was only 33.3%. The sensitivity and resistance breakpoints of tigecycline were set to ≤0.5 and ≥8 μg/mL, respectively, and the sensitivity and resistance rates were 50% and 0%, respectively. was susceptible to clarithromycin, amikacin, linezolid, moxifloxacin, rifampicin and rifabutin (100%). In Wenzhou, clarithromycin, amikacin and rifabutin have good antibacterial activity against MAC, while linezolid and moxifloxacin have high resistance. Amikacin and tigecycline have strong antibacterial activity against MAB, while most other antibacterial drugs are resistant to varying degrees. Most antibacterial drugs are susceptible to . and have good antibacterial activity. The identification of NTM species and the detection of their MICs have certain guiding values for the treatment of NTM lung disease.Key MessageThe three most common respiratory non-tuberculous mycobacterial (NTM) isolates with clinical significance in the Wenzhou area were tested for drug susceptibility. The broth microdilution method was used to determine the minimum inhibitory concentration distribution of antibacterial drugs and the susceptibility of NTM isolates to provide a reference basis for the clinical selection of an effective starting regimen.
Topics: Amikacin; Amoxicillin; Anti-Bacterial Agents; Cefoxitin; Ciprofloxacin; Clarithromycin; Clavulanic Acid; Doxycycline; Humans; Imipenem; Linezolid; Lung Diseases; Microbial Sensitivity Tests; Moxifloxacin; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Respiratory System; Rifabutin; Rifampin; Sulfamethoxazole; Tigecycline; Tobramycin; Trimethoprim
PubMed: 36120867
DOI: 10.1080/07853890.2022.2121984 -
Revista Argentina de Microbiologia 2022The aim of this study was to characterize phenotypically and genotypically 27 mecA positive Staphylococcus aureus strains with oxacillin MICs of ≤2μg/ml by Vitek 2,...
The aim of this study was to characterize phenotypically and genotypically 27 mecA positive Staphylococcus aureus strains with oxacillin MICs of ≤2μg/ml by Vitek 2, isolated in different regions of Uruguay. Susceptibility to oxacillin and cefoxitin was studied by gradient diffusion, disk diffusion to cefoxitin, and Phoenix and MicroScan systems. PBP2a was determined. SCCmec typing was performed and the isolates were compared by PFGE. Twenty-six isolates were susceptible to oxacillin; one strain was susceptible to cefoxitin by disk diffusion and 3 strains by gradient diffusion. Phoenix and MicroScan panels detected methicillin resistance in 25 and 27 strains, respectively. Twenty-six strains tested positive for PBP2a. Twenty-six strains carried SCCmec V and 24 belonged to pulsotype A. One strain carried SCCmec IV and did not belong to pulsotype A. Cefoxitin disk diffusion test and PBP2a detection correctly identified 26 of these 27 strains as MRSA. PFGE results suggest the dissemination of a cluster of MRSA carrying SCCmec V.
Topics: Humans; Oxacillin; Staphylococcus aureus; Cefoxitin; Uruguay; Anti-Bacterial Agents; Bacterial Proteins; Staphylococcal Infections; Microbial Sensitivity Tests; Methicillin-Resistant Staphylococcus aureus
PubMed: 35725665
DOI: 10.1016/j.ram.2022.05.004 -
BMC Microbiology Jul 2022The emergence of antimicrobial resistant bacteria in food producing animals is of growing concern to food safety and health. Staphylococci are common inhabitants of skin...
BACKGROUND
The emergence of antimicrobial resistant bacteria in food producing animals is of growing concern to food safety and health. Staphylococci are common inhabitants of skin and mucous membranes in humans and animals. Infections involving antibiotic resistant staphylococci are associated with increased morbidity and mortality, with notable economic consequences. Livestock farms may enable cross-species transfer of antibiotic resistant staphylococci. The aim of the study was to investigate antimicrobial resistance patterns of staphylococci isolated from livestock and farm attendants in Northern Ghana using phenotypic and genotypic methods. Antimicrobial susceptibility testing was performed on staphylococci recovered from livestock and farm attendants and isolates resistant to cefoxitin were investigated using whole genome sequencing.
RESULTS
One hundred and fifty-two staphylococci comprising S. sciuri (80%; n = 121), S. simulans (5%; n = 8), S. epidermidis (4%; n = 6), S. chromogens (3%; n = 4), S. aureus (2%; n = 3), S. haemolyticus (1%; n = 2), S. xylosus (1%; n = 2), S. cohnii (1%; n = 2), S. condimenti (1%; n = 2), S. hominis (1%; n = 1) and S. arlettae (1%; n = 1) were identified. The isolates showed resistance to penicillin (89%; n = 135), clindamycin (67%; n = 102), cefoxitin (19%; n = 29), tetracycline (15%; n = 22) and erythromycin (11%; n = 16) but showed high susceptibility to gentamicin (96%; n = 146), sulphamethoxazole/trimethoprim (98%; n = 149) and rifampicin (99%; n = 151). All staphylococci were susceptible to linezolid and amikacin. Carriage of multiple resistance genes was common among the staphylococcal isolates. Genome sequencing of methicillin (cefoxitin) resistant staphylococci (MRS) isolates revealed majority of S. sciuri (93%, n = 27) carrying mecA1 (which encodes for beta-lactam resistance) and the sal(A) gene, responsible for resistance to lincosamide and streptogramin. Most of the MRS isolates were recovered from livestock.
CONCLUSION
The study provides insights into the genomic content of MRS from farm attendants and livestock in Ghana and highlights the importance of using whole-genome sequencing to investigate such opportunistic pathogens. The finding of multi-drug resistant staphylococci such as S. sciuri carrying multiple resistant genes is of public health concern as they could pose a challenge for treatment of life-threatening infections that they may cause.
Topics: Animals; Anti-Bacterial Agents; Cefoxitin; Drug Resistance, Bacterial; Farms; Genomics; Ghana; Humans; Livestock; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Staphylococcus epidermidis
PubMed: 35864456
DOI: 10.1186/s12866-022-02589-9 -
Microbiology Spectrum Jun 2022The oxacillin- and cefoxitin-susceptible -positive Staphylococcus aureus is a novel "stealth" methicillin-resistant S. aureus (MRSA) type. Here, we sequenced the whole...
The oxacillin- and cefoxitin-susceptible -positive Staphylococcus aureus is a novel "stealth" methicillin-resistant S. aureus (MRSA) type. Here, we sequenced the whole genome of two oxacillin- and cefoxitin-susceptible -positive MRSA isolates from breast abscesses in a lactating woman and a nasal swab of a healthy student in Guangzhou for investigating the mechanism underlying its occurrence. The reversion of these isolates was selected by exposure to sub-MICs of cefoxitin with or without mupirocin. The expression of both parental strains and their revertants was determined, and the whole genome of the revertants was sequenced. Comparative whole-genome analyses performed for both strains revealed that of the clinical strain was mutated by a single-bp insertion at the 262nd position in the tandem repeat region of the gene, and this mutation that led to the formation of a premature stop codon. The colonizing strain was mutated by a novel G-to-A base substitution in the second promoter region (-35 bp) of . The expression level of strain 697 revertant was 37 times higher than that of the parental strain. Although the expression level was even higher for parental strain 199 compared with that for its revertant, its cDNA sequence contained a single-bp insertion. Collectively, both the missense and single substitution mutations of the second promoter of could render MRSA isolates as "stealth" MRSA, thereby emphasizing the importance of combining phenotype tests with or penicillin-binding protein 2a detection for the identification of MRSA. The oxacillin- and cefoxitin-susceptible -positive Staphylococcus aureus is a novel type of "stealth" methicillin-resistant S. aureus (MRSA), which is difficult to be detected using conventional methods. To investigate the genomic basis of their occurrence, we sequenced the whole genome of two previously recovered oxacillin- and cefoxitin-susceptible -positive MRSA isolates from breast abscesses in a lactating woman and a nasal swab of a healthy student in Guangzhou. Complete SCC structure was absent except for in clinical isolate 199. Additionally, a novel single-base pair insertion was observed in the clinical strain, which resulted in premature termination and a frameshift mutation. The colonizing isolate 697 had a Scc--type IVa, and the second promoter region (-35 bp) of was mutated by a novel G-to-A base substitution. The reversion of oxacillin- and cefoxitin-susceptible -positive S. aureus to resistant MRSA isolates was selected by exposure to subminimum inhibitory cefoxitin with or without mupirocin.
Topics: Abscess; Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Female; Genomics; Humans; Lactation; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mupirocin; Oxacillin; Penicillin-Binding Proteins; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35608351
DOI: 10.1128/spectrum.00291-22 -
MSphere Apr 2023Mycobacteroides abscessus is an opportunistic pathogen in people with structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and...
Mycobacteroides abscessus is an opportunistic pathogen in people with structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis. Pulmonary M. abscessus infection causes progressive symptomatic and functional decline as well as diminished lung function and is often incurable with existing antibiotics. We investigated the efficacy of a new tetracycline, omadacycline, in combination with existing antibiotics recommended to treat this indication, in a mouse model of M. abscessus lung disease. Amikacin, azithromycin, bedaquiline, biapenem, cefoxitin, clofazimine, imipenem, linezolid, and rifabutin were selected as companions to omadacycline. M. abscessus burden in the lungs of mice over a 4-week treatment duration was considered the endpoint. Omadacycline in combination with linezolid, imipenem, cefoxitin, biapenem, or rifabutin exhibited early bactericidal activity compared to any single drug. Using three M. abscessus isolates, we also determined the frequency of spontaneous resistance against omadacycline to be between 1.9 × 10 and 6.2 × 10 and the frequency of persistence against omadacycline to be between 5.3 × 10 and 1.3 × 10. Based on these findings, the combination of omadacycline and select drugs that are included in the recent treatment guidelines may exhibit improved potency to treat M. abscessus lung disease. M. abscessus disease incidence is increasing in the United States. This disease is difficult to cure with existing antibiotics. In this study, we describe the efficacy of a new tetracycline antibiotic, omadacycline, in combination with an existing antibiotic to treat this disease. A mouse model of M. abscessus lung disease was used to assess the efficacies of these experimental treatment regimens. Omadacycline in combination with select existing antibiotics exhibited bactericidal activity during the early phase of treatment.
Topics: Animals; Mice; Mycobacterium abscessus; Linezolid; Cefoxitin; Microbial Sensitivity Tests; Anti-Bacterial Agents; Tetracyclines; Imipenem; Rifabutin; Cystic Fibrosis
PubMed: 36912629
DOI: 10.1128/msphere.00665-22 -
Journal of Clinical Microbiology Dec 2019Methicillin (β-lactam) resistance in is mediated by the gene, with resistance reported to be as high as 90%. The goal of this study was to evaluate oxacillin and...
Evaluation of Oxacillin and Cefoxitin Disk Diffusion and Microbroth Dilution Methods for Detecting -Mediated β-Lactam Resistance in Contemporary Staphylococcus epidermidis Isolates.
Methicillin (β-lactam) resistance in is mediated by the gene, with resistance reported to be as high as 90%. The goal of this study was to evaluate oxacillin and cefoxitin disk diffusion (DD) and broth microdilution (BMD) methods for the detection of -mediated β-lactam resistance in 100 human isolates of (48 -positive isolates and 52 negative isolates). Oxacillin DD tests using the Clinical and Laboratory Standards Institute (CLSI) M100-S28 breakpoints for / accurately differentiated -positive and -negative isolates, with categorical agreement (CA) of 100% and no very major errors (VMEs) or major errors (MEs) identified. Likewise, oxacillin BMD and cefoxitin DD tests using the coagulase-negative species (CoNS) breakpoints were highly reliable for detecting -mediated β-lactam resistance in isolates. For cefoxitin DD and BMD results interpreted using / breakpoints, the CA was 97.6% and 96.2%, respectively. There were 4.9% VMEs for cefoxitin DD with 0% MEs, and 3.6% VMEs and 3.9% MEs for cefoxitin BMD. Oxacillin BMD using / breakpoints yielded the highest VMEs at 17.4% and 90% CA. Our findings demonstrate that oxacillin DD tests using the CLSI M100-S28 breakpoints for / and oxacillin BMD and cefoxitin DD tests using the CoNS breakpoints reliably identified -mediated β-lactam resistance in Using PCR as the gold standard, the PBP2a SA culture colony test (Abbott Diagnostics) exhibited 100% sensitivity and specificity whereas 2 false negatives were identified using the PBP2' latex agglutination test kit (Thermo Fisher Scientific) with sensitivity and specificity of 95.8% and 100%, respectively.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Humans; Microbial Sensitivity Tests; Oxacillin; Polymerase Chain Reaction; Sensitivity and Specificity; Staphylococcal Infections; Staphylococcus epidermidis; beta-Lactam Resistance
PubMed: 31462553
DOI: 10.1128/JCM.00961-19