Beta-lactam Research Articles

1980. A Case Series of Serratia Marcescens Endocarditis in Persons Who Inject Drugs

Abstract Background Serratia marcescens is a gram-negative bacillus that is widespread in the environment and has been recognized as a rare cause of infective endocarditis (IE), particularly in persons who inject drugs (PWID). The literature consists of a 19 person case series in the 1970s followed by just a handful of case reports and small case series. At AHWFB (Atrium Health Wake Forest Baptist), we have noticed an increasing number of severe infections, including IE, with Serratia marcescens in PWID. Methods We conducted a retrospective chart review of all cases of Serratia grown from sterile culture sites in the AHWFB system between 8/1/2016 -10/31/2021. Charts were reviewed to confirm status of injection drug use in the 3 months prior to admission, ≥18 years old, and possible or definite IE by Modified Duke’s criteria. Results Twenty two participants were included in the study. The median age was 29.5 years. Eighteen (90%) were white and 16 (73%) were female. Sixteen (73%) had injection of opioids and 3 (14%) had injection of stimulants clearly indicated. Ten (45.5%) had stimulant use documented but the route was not clear. Nineteen (95%) had evidence of active or resolved HCV infection. The median duration of bacteremia was 2 days. Two cases of IE involved the aortic valve, 8 mitral, 3 pulmonic, and 10 tricuspid. Four (18%) of the participants had prosthetic valve IE. Nine (41%) of the participants had a history of previous IE episode. Eighteen participants had evidence of septic emboli: 10 pulmonary, 7 cerebral, and 5 major arterial. In terms of disposition, 4 (18%) patients died, 4 left against medical advice, 12 (54%) remained at a facility for the duration of their antibiotics. One patient was transferred to another facility and one was discharged to complete antibiotic therapy via peripheral IVs in an infusion center. Two patients expired before a final antibiotic regimen could be determined. Ten participants were treated with beta lactam monotherapy, 1 with fluoroquinolone monotherapy, and 9 with dual therapy with a beta lactam and fluoroquinolone. Conclusion Serratia marcescens, a rare cause of IE, has been found in a population of PWID in a North Carolina hospital system. More research is necessary to understand why this unusual infection is clustering in this population and the optimal treatment regimen. Disclosures All Authors: No reported disclosures.

1833. Evaluating the Impact of Reported Beta-Lactam Allergies on Clinical Outcomes in Gram-Negative Bloodstream Infections: A Retrospective Cohort Study

Abstract Background Approximately 15% of hospitalized patients are labeled as beta-lactam (BL) allergic. Despite this, it is estimated that > 90% of patients do not have clinically significant hypersensitivity reactions and are BL-tolerant. The BL allergy label is associated with a host of downstream consequences, including receipt of suboptimal antibiotic therapy, healthcare-associated infections, and bacterial resistance. There are limited data investigating the impact of this allergy label on clinical outcomes in bloodstream infections caused by Gram-negative pathogens (GN-BSI). Methods This was a retrospective, single center, cohort study evaluating the impact of BL allergies on clinical outcomes in patients with GN-BSI from January 2017 to August 2021. Adult inpatients with index blood cultures positive for Pseudomonas species or Enterobacterales who received intravenous antibiotics with Gram-negative activity were included. The primary endpoint was time to effective therapy (defined as treatment with in vitro activity against a causative pathogen, as determined by phenotypic susceptibilities) and the key secondary endpoint was 30-day all-cause mortality. Results Overall, 120 patients were included, representing 30 BL-allergic (BL-A) and 90 BL-non-allergic (BL-NA) patients. Blood cultures positive for Pseudomonas species or Enterobacterales were evenly distributed (Table 1). Among Enterobacterales, Escherichia coli was implicated in 25% of cases overall. The most common source of infection was intra-abdominal infection. Across groups, median quick Pitt Bacteremia Score was 1 (IQR 0-2). Infectious Diseases was consulted in 37% of BL-A patients vs. 29% of BL-NA patients. Of BL allergies reported, 86% were classified as likely immunoglobulin E (IgE) mediated reactions. Allergy was not consulted in any of these cases. Median time to effective therapy was 162 minutes (IQR 20-824 minutes) vs. 103 minutes (IQR 27-775 minutes) in the BL-A and BL-NA groups, respectively. Thirty-day mortality occurred in 31% of BL-A and 21% of BL-NA patients. Conclusion Increased time to effective therapy and mortality rates were observed among patients with reported BL allergies. These findings highlight the importance of allergy clarification in antibiotic stewardship. Disclosures Kathleen Degnan, MD, Gilead: Grant/Research Support.

1693. Meropenem-Xeruborbactam: In Vitro Potency against Gram-Negative Bacteria in Comparison with Marketed and Investigational Beta-lactam (BL)/Beta-lactamase Inhibitor (BLI) Combinations

Abstract Background Several BLI combinations have entered into clinical testing or been approved for use but there are few comparative studies of their in vitro activity. Xeruborbactam (XER, formerly QPX7728) is a cyclic boronate BLI with potent inhibitory activity against serine and metallo-beta-lactamases (MBL). It is in clinical development in combination with meropenem (MEM). The objective of this study was to compare in vitro potency of MEM-XER to that of other investigational and approved BL/BLI combinations in head-to-head testing against recent isolates of carbapenem-resistant Enterobacterales (CRE) and Acinetobacter baumannii (CRAB) as well as Pseudomonas aeruginosa (PA). Methods The test panel of recent worldwide isolates consisted of 507 CRE including 168 MBL producers (157 NDM, 11 VIM, 1 IMP), 506 CRAB, and 506 PA that were representative of current isolates and included 65 MDR (resistant to ≥ 3 antimicrobial classes) strains. MEM-XER was tested with XER at a fixed 8 mg/L conc. and other BL/BLI combinations at their recommended BLI concentrations. MIC testing was conducted blinded to drug identity using CLSI reference methods and controlled using approved quality control bacterial strains and ranges. Results The MIC50 and MIC90 for MEM-XER vs CRE ranged from ≤ 0.03 mg/L to 0.06 mg/L and 0.06 mg/L to 1 mg/L, respectively. MEM-XER and cefepime-taniborbactam (FEP-TANI) were the only BL/BLIs with activity against MBL-producers; based on MIC90, MEM-XER (MIC90 of 1 mg/L) was 16-fold more potent than FEP-TANI (MIC90 of 16 mg/L). MEM-XER and sulbactam-durlobactam (SUL-DUR) were the only agents with high potency against CRAB, with MIC50/MIC90 of 0.5/4 mg/L and 1/2 mg/L. For the representative panel of PA, the potency of MEM-XER, FEP-TAN, ceftolozane-tazobactam (TOL-TAZ), imipenem-relebactam (IMP-REL), and CAZ-AVI was similar with MIC90s ranging between 2-8 mg/L; for the MDR panel, MIC90‘s were > 8 mg/L for all combinations, with MER-XER, IMP-REL, TOL-TAZ, and CAZ-AVI having MIC50’s of 2-4 mg/L. Conclusion Compared to the marketed or investigational BL/BLIs, MEM-XERU had the broadest coverage of carbapenem-resistant gram-negative bacteria, with the most differentiating property being activity against multiple strains of MBL-producing CRE and CRAB. Disclosures Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Jill Lindley, BS, AbbVie: Grant/Research Support.

930. Weakening the waves: Impact of a syndrome-based antimicrobial stewardship intervention during COVID-19

Abstract Background Lower respiratory tract infections (LRTIs) from SARS-CoV-2 are difficult to distinguish from other viral or bacterial etiologies. This has led to increased antimicrobial use (AU) during the pandemic and concerns for concomitant rise in antimicrobial resistance (AMR). It is crucial for antimicrobial stewardship (ASP) to develop strategies to mitigate excess AU and curve AMR. We leveraged a syndrome-based ASP intervention targeting LRTIs and the use of anti-Pseudomonal beta lactams (APBL) during the COVID-19 pandemic. Methods We incorporated COVID-19 elements into a syndrome-based prospective audit and feedback (PAF) at an urban community hospital. Elements included EMR order sets (Figure 1) that discouraged routine AU for COVID-19 and PAF targeting LRTIs and COVID-19 therapies. Empiric selection discouraging APBL was incorporated during the first COVID-19 wave. Order sets and PAF were then modified to reflect novel COVID-19 therapeutics and AU was strongly discouraged in subsequent waves. Data on AU and AMR from 2018-2022 was reviewed. Figure 1.Electronic medical records COVID-19 antimicrobial order set Results Average quarterly AU increased during the first pandemic year by 8.7%, from 359.5 to 391 days of therapy per 1000 patient days (DOT/1000), with peaks 22.5% above the pre-pandemic average during COVID-19 surges. AU increased each COVID-19 surge, with smaller peaks each subsequent wave. DOT/1000 declined 29% from the first wave to the Omicron wave. AU decreased the second year to 318, an 18.6% decrease from the first pandemic year. Ceftriaxone use increased during surges, reflecting our LRTI guidelines (Figure 2). Peaks declined each subsequent wave, from a peak of 239 in the first wave to 75 during Omicron, a 68% decrease. The average monthly DOT/1000 for APBL decreased from 73.51 to 63.21 (Figure 3). Incidence rate of ESBL and CRE initially rose and then declined (Figure 4). Figure 2.Antimicrobial use (DOT/1000) before and during the COVID-19 pandemicFigure 4.Antipseudomonal beta lactam use before and during the COVID-19 pandemic Figure 5. Incidence of multidrug resistance organisms before and during the COVID-19 pandemic Conclusion ASP successfully incorporated COVID-19 elements and steered AU during the pandemic. Though total AU increased, APBL use declined and AU peaks decreased with each COVID-19 wave, reflecting adherence with ASP recommendations. AMR increased during the first year and subsequently declined. ASP can play a vital role guiding AU during respiratory pandemics. Disclosures All Authors: No reported disclosures.

779. PIDS Featured Oral Abstract: High Beta Lactam Exposure in Neonates with Bloodstream Infection Associated with Intestinal Dysbiosis and Enterococcus spp. Abundance in the Gut Microbiome

Abstract Background To characterize how antibiotic exposure impacts development and durability of intestinal dysbiosis and the acquisition of antibiotic resistance genes (ARGs) in the intestinal flora of premature infants in the Neonatal Intensive Care Unit (NICU), we established an infant gut microbiome biorepository (IGMB). Methods We performed prospective weekly stool collection in NICU patients meeting the following criteria: birthweight < 2000 g, postnatal age < 2 months and no diagnoses of congenital gut malformation or cyanotic heart disease. Cases were infants with bloodstream infections (BSI), defined as bacterial growth from blood culture; controls were infants with < 5 days of antibiotic exposure, no BSI nor necrotizing enterocolitis. We performed metagenomic analysis on 5–6 serial stool samples from each of the 10 cases and 10 controls (n= 100 stools). We used Wilcoxon rank sum tests for pairwise comparisons. Results From July 2021 to May 2022, 265 infants contributed 1,300 stool samples to the IGMB. In 7 of 8 BSI cases the causative pathogen was identified in the pre-BSI stool sample. Two more BSI cases did not have a pre-BSI stool sample. Microbiome species α-diversity increased with advancing postnatal age in controls but not in cases (Fig. 1). Among 6 cases with high beta lactam exposure ( >14 cumulative days by last stool collection), 3 had notable increases in the relative abundance of Enterococcus spp. (Fig. 2). Controls did not have similar trends in Enterococcus spp., but did have higher relative abundance of facultative anaerobes including Bifidobacterium, Lactobacillus, and Veillonella spp. (Fig. 3). Antibiotic resistance gene (ARG) abundance did not differ significantly between cases and controls. Conclusion Compared to controls, neonates with BSI have increased antibiotic intensity throughout their NICU admissions, reduction of microbial species diversity and overabundance of specific organisms in their gut microbiomes. We observed increased Enterococcus spp. prevalence with higher beta lactam exposure. ARG abundance did not differ between cases and controls. The clinical implications of this microbiome dysbiosis warrant further study. Disclosures Jörn-Hendrik Weitkamp, MD, Roche Diagnostics: Advisor/Consultant.

137. Comparison of genotypic resistance pattern between Enterococcus faecium and Enterococcus faecalis to better understand the occurrence of mutations.

Abstract Background Enterococcus is one of the major causes of nosocomial infections many with vancomycin resistance. About 50,000 infections are reported per year due to vancomycin-resistant Enterococci. Understanding the genotypic mutations can help recognize the potential burden for antibiotic resistance that exists in a population. In this study, using whole genome sequencing (WGS) we aim to analyze the prevalence of genetic resistance markers for commonly used antibiotics for Enterococcal treatment. Methods Whole genome sequencing was performed using the NextSeq (Illumina Inc., CA) on 60 isolates of E. faecium and 29 isolates of E. faecalis. The isolates were obtained from two different Detroit area hospitals from 2017-2019. The data from WGS was analyzed using EPISEQ CSTM (BIOMÉRIEUX, Marcy l ‘Etoile, France) bioinformatic database to obtain specific resistance genes which would correspond to commonly used antibiotics for treatment of Enterococcal infections. Results Among the 89 Enterococcus faecium and Enterococcus faecalis investigated, we identified a total of 33 unique resistance genes across 18 classes of antibiotics (Table 1). We detected genetic mutations efmA, pbp5, tet(L), liar, liaS unique to E. faecium and only emeA unique to E. faecalis. E. faecium and E. faecalis share 14 similar resistance genes. E. faecium and E. faecalis had 12 and 7 unique resistance genes, respectively but are of same drug classes. The most common antibiotic classes include aminoglycosides, tetracyclines, quinolones, beta-lactams, glycopeptides, macrolides, and pyrimidine analogs. Table 1:Enterococcus faecium and E. faecalis genetic mutations and drug class resistance Conclusion Enterococcus faecium had a greater number of resistance genes with glycopeptide, aminoglycoside, and beta lactam resistance when compared to Enterococcus faecalis. Whereas Enterococcus faecalis had more resistance genes associated with macrolides, tetracyclines, pyrimidine analogs, and Bactrim. In general, both appear to have many genes that encode for resistance to major classes of antibiotics which are used for treatment of Enterococcal infections. Further comparison with phenotypic susceptibility testing data would help better understand the practical implications of our resistance gene testing. Disclosures Piyali Chatterjee, PhD, AHRQ Grant # 1R03HS027667-01: Grant/Research Support|AHRQ Grant # 1R03HS027667-01: Central Texas Veterans Health Care System Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|GlaxoSmithKline plc.: Receiving symposia honoraria|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502|Merck: Advisor/Consultant|qpex: Advisor/Consultant|Shionogi: Grant/Research Support|Spero: Advisor/Consultant Chetan Jinadatha, MD, MPH, AHRQ R01 Grant-5R01HS025598: Grant/Research Support|EOS Surfaces: Copper Coupons and materials for testing.

1740. Antibiotic Allergy Delabeling in Pediatric Infectious Disease Clinic: Missed Stewardship Opportunities

Abstract Background Reported beta lactam antibiotic allergies are common, with up to 10% of individuals carrying a penicillin [PCN] allergy label and approximately 1% carrying a cephalosporin allergy label. However, >90% of patients with a PCN allergy label can safely tolerate penicillins. Incorrect antibiotic allergy label can contribute to increases in antibiotic resistance and medication side effects. Appropriate medication allergy history taking is necessary and sometimes sufficient to effectively remove inappropriate allergy labels. We aimed to evaluate opportunities for addressing inappropriate PCN allergy labels in a pediatric infectious diseases clinic. Methods Electronic medical records (EMRs) for patients seen in an academic outpatient pediatric infectious diseases clinic from January 1, 2021 through April 30, 2021 were reviewed for presence of documented antibiotic allergy at time of visit, antibiotic class (PCN, cephalosporin [Ceph.], or non-beta lactam), reaction type, documentation of full reaction history needed to stratify for potential delabeling, and whether or not potential allergy delabeling was addressed during the visit. Results Antibiotic allergy labels were present in the EMR in 18% (n=16) of the 90 encounters reviewed, representing 19% (n=15) of patients seen. Beta lactam antibiotic reactions accounted for 69% (11/16) of documented allergies; 8 PCN class (73%), 2 Ceph. class (18%), 1 with both PCN and Ceph. class allergy (9%). Reactions included rash (6 visits; 54%), hives (3; 27%), nausea/vomiting (1; 9%), diarrhea (1; 9%), swelling (1; 9%), and none recorded (2; 18%). [Sum >100% due to multiple reactions listed]. No additional reaction history was obtained for any patient during the visits. Antibiotic allergy delabeling or assessment by an allergist was only addressed during 1 of the 16 visits with documented antibiotic allergy (6.3%). Conclusion Antibiotic allergy labels are common in pediatric infectious diseases clinic patients. However, appropriate medication allergy histories and the potential for allergy delabeling were not documented for the majority of patients with antibiotic allergy labels. This represents a significant missed opportunity for antibiotic allergy delabeling and a target for future antimicrobial stewardship opportunities. Disclosures All Authors: No reported disclosures.

413. Cost effectiveness of rectal screening for ESBL producing organism in preventing urosepsis following transrectal prostate biopsy

Abstract Background Urosepsis following transrectal ultrasound guided prostate biopsy (TRUS PB) occurs in 0.3-3.1% of patients. Our center gives ciprofloxacin and ceftriaxone prophylaxis. With rise in urinary pathogens resistant to fluoroquinolones or producing extended spectrum beta lactam (ESBL+), prophylactic regimen might need changing. Studies have highlighted cost effectiveness of rectal screening for ESBL+ organism prior to TRUS PB to determine target antibiotic. We compare our center’s incidence of urosepsis admissions following TRUS PB to the expected rate and calculate cost-effectiveness of pre-procedure screening to prevent urosepsis admissions. Methods All patients with CPT billing code 55700 (biopsy, prostate; needle or punch, single or multiple, any approach) from January 2020 through January 2021 were identified retrospectively. Charts were queried for emergency department or urgent care visits and hospital admissions within two weeks of TRUS PB and admissions reviewed for evidence of urosepsis and ESBL+ cultures. Hospitalization cost was compared to the extrapolated cost of doing pre-procedural rectal swabs. Cost of rectal swab and culture was estimated at $39.02 per swab, and identification and susceptibility at $67 per isolate. Results 33 of 1593 patients presented to our institution within 2 weeks of TRUS PB over a 13 month period. 3 were admitted for urosepsis post TRUS PB (2 with ESBL+ infection, 1 with no growth on culture), 12 had ED visits relating to their TRUS PB without urosepsis, (2 due to UTI with other organisms) and 18 visits were unrelated to TRUS PB. Our urosepsis admission rate was 0.19% (for ESBL+ 0.13%). Cost of the 3 hospitalizations was $37,910.92 ($27,063.76 for 2 ESBL+ infections). Rectal swabs would in theory have prevented 2 admissions. Cost of swab and culture would be $62,158.86. 50% of the swabs would need further testing to identify ESBL+ organism, for an additional cost of $53,365.50. Conclusion Given lower than expected urosepsis admission rates at our institution after TRUS PB, pre-procedure rectal swabs would not be cost effective, especially since some admissions may be unavoidable. The cost analysis is an underestimate as a visit some days prior to procedure would be scheduled and the staff resource utilization to collect the swab is not accounted for. Disclosures All Authors: No reported disclosures.

The Safety of the Direct Drug Provocation Test in Beta-Lactam Hypersensitivity in Children: A Systematic Review and Meta-Analysis

Direct drug provocation test (DPT) without prior skin testing (ST) has been investigated in children suspected of being at risk for beta-lactam (BL) hypersensitivity reaction (HSR). However, no systematic review and meta-analysis has investigated the efficacy and safety of direct DPT for BL-HSR in children. To investigate the prevalence of BL-HSR by direct DPT and the safety of direct DPT in children. We searched MEDLINE, EMBASE, Web of Science, and CINAHL from their inception to July 23, 2022, for studies that performed direct DPT in children with suspected BL-HSR, or for studies that performed DPT in all cases with ST results, but they ignored the ST results. The true prevalence was defined as the proportion of children who experienced an HSR during direct DPT. Safety was determined according to the proportion of children who developed a dangerous reaction following DPT. Twenty-eight studies with 8,334 direct challenges were included. Fifteen studies included patients who presented with either immediate or nonimmediate HSR, and the majority of the index reactions were nonsevere. Amoxicillin/amoxicillin-clavulanic acid was the most commonly used during the DPT. The pooled prevalence of confirmed BL-HSR was 5.23% (95% CI 4.17-6.39; I2= 72%). Immediate and nonimmediate HSR were reported in 0.8% (95% CI 0.43-1.25; I2= 55.1%) and 3.69% (95% CI 2.66-4.87; I2= 79.77%), respectively. Severe reactions were found in 3 cases with the frequency of 0.036% (95% CI 0.012-0.112; I2= 0%). The prevalence of BL-HSR by direct DPT was 5.23%, and the frequency of severe reactions from direct DPT was very low (0.036%). Our findings support direct DPT as a safe and effective delabeling tool in children with suspected nonsevere BL-HSR.

Outcomes of Beta-Lactam Allergic and Non-Beta-Lactam Allergic Patients with Intra-Abdominal Infection: A Case-Control Study.

In the case of intra-abdominal infections (IAI) in beta-lactam (BL) allergic patients, empiric antimicrobial therapy without BL is recommended; however, data regarding the outcome with alternative regimens are scarce. This study aimed to compare the outcomes of BL allergic (BLA) patients with IAI to those who were non-BLA (NBLA). We conducted a case-control study in a French teaching hospital, between 1 January 2016 and 31 August 2021. BLA patients with IAI treated with fluoroquinolone or aztreonam and metronidazole were matched with controls treated with BL, on age, sex, disease severity, IAI localization, and healthcare-associated infection (HAI) status. We compared rates of therapeutic failures, adverse events, and HAI, and then assessed factors associated with therapeutic failure using a logistic regression model. The therapeutic failure rate was 14% (p > 0.99) in both groups of 43 patients, and there was no significant difference in the adverse events rate (p > 0.99) and HAI rate (p = 0.154). Factors independently associated with therapeutic failure were higher BMI (OR 1.16; 95%CI [1.00-1.36]; p = 0.041), longer hospital length of stay (OR 1,20; 95%CI [1.08-1.41]; p = 0.006), and inadequate empiric antimicrobial therapy (OR 11.71; 95%CI [1.43-132.46]; p = 0.025). The outcomes of BLA patients with IAI treated without BL were the same as those for NBLA patients treated with BL.

Phytochemical Content and Antibacterial Effect of Ethanolic and Methanolic Extracts of Pleurotus ostreatus Mushroom

Aims: Microbial resistance is a threat to the successful treatment of microbial infections. Mushrooms are known to possess antimicrobial and antioxidant potential which could be inhibitory to some pathogenic organisms. The aim was to assess the phytochemicals and antimicrobial potential of Pleurotus ostreatus extracts on some pathogenic organisms.
 Methodology: The study was conducted at the Bells University of Technology, Nigeria, between December 2019 and August 2020. A 10% dried powder of Pleurotus ostreatus was extracted in absolute ethanol and methanol and evaporated in a water bath at 50 oC. Extracts were reconstituted in dimethyl Sulfoxide (DMSO) at 12.5, 25, 50, and 100% respectively. Antibiotic effects of extracts were tested on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus saprophyticus by agar well diffusion method and compared with standard antibiotic discs. DMSO and the solvents served as positive and negative controls. Ethanolic extract was subjected to Gas Chromatography-Mass Spectrometer.
 Results: The extracts exhibited varying inhibitory effects on the organisms except on E coli at 12.5% ethanolic extract. The inhibition zones increased with extract concentration from 2-12 mm and 4-14 mm in ethanolic and methanolic extracts respectively. The inhibitory effect of standard antibiotics was higher 17-25 mm except for erythromycin (13-14 mm). Test organisms were resistant to Beta Lactams (augmentin, cefuroxime, and ceftazidime) and sensitive to Aminoglycoside (gentamicin), Fluoroquinolones (ofloxacin), Ciprofloxacin, and erythromycin. GC/MS revealed the presence of 30 organic compounds, amongst them were sugar, sugar alcohols, alkaloids, amines, fatty acids, esters, aldehydes, and alcohols. The most abundant were oleic acid (33.75%) and 9-octadecenoic acid (Z)-2-hydroxy-1- (21.21%). Phytochemicals are heterocyclic compounds found in natural products.
 Conclusion: P. ostreatus has been revealed to possess phytochemicals of medical relevance with potential for pharmacological application. The implication is that Pleurotus ostreatus extracts could serve as a lead to novel drug discoveries which could enhance health and nutritional well-being.

A Meta-analysis of Mortality Factors in Patients with Klebsiella Pneumoniae Bloodstream Infection

Objective: To systematically analyze the risk factors for bloodstream infections (BSI) of Klebsiella pneumoniae (KP) and its adverse prognosis (death), and provide theoretical basis for improving clinical prevention and control efficiency and reducing mortality. Methods: The literatures related to KP BSI risk factors and death risk factors were searched in CNKI, Wanfang, VIP, PubMed and Cochrane databases. Relevant literatures were screened according to inclusion and exclusion criteria, and the quality evaluation and data extraction were carried out for the finally included literatures. Meta-analysis was conducted by STATA12.0 software. Results: A total of 9 literatures were included with a total sample size of 2014, all of which were retrospective studies with NOS scores of 7-9.Meta analysis showed that: the history of hospitalization, history of ICU stay, high blood pressure, heart disease, kidney disease, lung disease, liver abscess, hypoalbuminemia, hemodialysis, mechanical ventilation, deep venipuncture, indwelling gastric tube, parenteral nutrition, placing a urinary catheter use radiotherapy/ chemotherapy, hormone and immune inhibitor use, antibiotics (beta lactam, carbon green alkene, quinolone, for ring element, cephalosporins) the use of the difference between groups was statistically significant (P < 0.05).Publication bias showed that ICU admission history, hypertension, and malignant tumors were biased. After the one-way study was adopted, ICU admission history and hypertension had no significant bias, which was accepted. Conclusion: the history of hospitalization, history of ICU stay, high blood pressure, heart disease, kidney disease, lung disease, liver abscess, hypoalbuminemia, hemodialysis, mechanical ventilation, deep venipuncture, indwelling gastric tube, parenteral nutrition, placing a urinary catheter use radiotherapy/ chemotherapy, hormone and immune inhibitor use, antibiotics (beta lactam, carbon green alkene, quinolone, for ring element, cephalosporins) the use of KP is the major risk factors of death in patients with bloodstream infections.

Differences in beta-lactam and penicillin allergy: Beyond the West and focusing on Asia-Pacific.

Beta-lactam (BL) antibiotic "allergy" labels are common, but often overdiagnosed. Although much research has been focused on the BL allergy and the delabelling process in the West, studies from other parts of the world remain sparse. This review outlines the contrasting global epidemiology, shifting clinical practices and disparities of BL allergy in the Asia-Pacific region compared with the West. Innovative strategies to overcome barriers in BL allergy workup are discussed and potential directions for future research and service development are also proposed.

Antibiotic choice for respiratory infection in pediatric

Respiratory infection (RTI) is one of the leading factors of death in children in India. In most countries, RTI is a common cause of hospitalisation in children under five years old. There are different guidelines for management of various type of RTI. Most of these, emphasis on use of antibiotics in specific sub type of RTI. While literatures recommend avoiding antibiotic in viral infections, they mostly suggest beta lactams as first line drugs. Depends on patients, amoxicillin remains drug of choice for most of out-patients. In case of hypersensitivity to penicillin, cephalosporin commonly will be substituent. If specific and atypical organism found, need to switch to other type such as macrolides. In this research, we aimed to briefly review current guidelines and literatures regarding antibiotic selection in paediatrics suffering from different type of respiratory tract infection.

Molecular Screening of Extended Spectrum β-lactamases in Klebsiella pneumoniae isolated from Clinical Sources

Klebsiella pneumoniae is a major pathogen responsiple for nosocomial infections in world hospitals . One of the causes for the drug resistance in the Klebsiella pneumoniae is the production of ESBls enzymes.This research documented TEM , SHV , and CTX-M for the first time among Klebsiella pneumoniae in Al-Anbar hospitals of Iraqi. All studied clinical isolates of K. pneumoniae (30) resistant- beta lactam from 100 isolates were collected from different clinicals sources such as (burned, wounds, sputum,and urine samples). The susceptibility to different antibiotics was tested by VITEK-2 system. The bla TEM , SHV , and CTX-M genes were detected by conventional PCR and the result showed 30/30 (100%) strains harbored these genes. This results showed the coexistence of these genes in one strains of K. pneumoniae, while indicated widespread ESBLs in Anbar, Iraq.

Intracellular uropathogenic Escherichia coli are undetectable in urinary bladders after oral mecillinam treatment: An experimental study in a pig model of cystitis

ObjectivesExperiments in murine models of urinary tract infection (UTI) show that uropathogenic Escherichia coli (UPEC) form bacterial reservoirs in the bladder tissue that can survive beta lactam antibiotics and give rise to reinfection. The observed reinfection cascade suggests intracellular bacterial persistence as a possible explanation for recurrent UTI in humans. To test this hypothesis in an animal model closer to humans, we here investigated whether UPEC infecting the bladders of experimentally inoculated pigs are able to survive standard oral mecillinam treatment. Moreover, we analyzed the infected pig bladders by microscopy for the presence of intracellular UPEC colonies. MethodsSeven pigs were experimentally inoculated with the UPEC cystitis strain, UTI89, to induce cystitis. After 5 days of infections, a 3-day oral treatment with the extracellularly active β-lactam, mecillinam, was initiated. The infection was monitored with regular urine and blood samples. When terminated, whole bladders were removed and homogenized to quantify viable intracellular bacteria. In addition, two pigs were inoculated with UTI89pMAN01 constitutively expressing green fluorescent protein and the bladders subsequently analyzed by microscopy for bacterial location and morphology. ResultsExperimental inoculation resulted in cystitis in all animals. After 3-day treatment with mecillinam, no viable UPEC were detectable in urine or bladder homogenates. Microscopy analysis of pig bladders at 12 h post infection, revealed no detectable intracellular bacterial colonies and no filamentous UPEC phenotypes were identified. ConclusionsPigs experimentally infected with UPEC completely clear their infection upon mecillinam treatment, which contrasts earlier findings from similar experiments in mice. Moreover, the hallmarks of induced UTI in mice, i.e. intracellular bacterial communities and bacterial filamentation, could not be identically reproduced in a pig model of acute UTI. This result suggests that significant differences might exist between UTI in mice and larger mammals, and therefore perhaps also between mice and humans. Additional studies are needed to reveal details on the Escherichia coli acute UTI pathogenesis cascade in larger mammals to assess to which extent observations in mice can be transferred to humans.

Overprediction of Carbapenemase-Containing Isolates by an Automated AST Instrument's Computer Algorithm.

The VITEK® 2 is generally accepted as a reliable method for predicting antibiotic resistance mechanisms including aminoglycoside phenotypes, beta lactam phenotypes, impermeability, and penicillinases. However, when it comes to predicting carbapenemases, the research that has been done is inconsistent in both methods and results. We compared the predictions of the VITEK 2 and Advanced Expert System™ (AES) with the results of the modified carbapenemase inactivation method in an academic medical center lab to evaluate the clinical reliability of the VITEK 2 and AES in routine workflow for the detection of carbapenemases. Our findings show that the positive predictive value of carbapenemase detection on the VITEK2 and AES is 30.3% (91/300) in our patient population. In light of these results, we propose that the VITEK 2 and AES be used as a screening tool for carbapenemase-containing organisms rather than as a definitive test.

DESCRIPTION AND ANTIBIOTIC RESISTANCE OF BACTERIA ISOLATED FROM SPUTUM SPECIMENS AT CAN THO UNIVERSITY OF MEDICINE AND PHARMACY HOSPITAL FROM JULY 2021 TO DECEMBER 2021

Background: Bacteria causing respiratory infections tend to rapidly increase antibiotic resistance, prolong treatment time, increase treatment costs and increase mortality. Objectives: 1). To determine the proportion of bacterial strains isolated from sputum specimens; 2). To describe the antibiotic resistance of bacterial strains isolated from sputum specimens. Materials and methods: A cross-sectional descriptive study was carried out on 96 patients with positive sputum cultures using convenient sampling method. Results: Streptococcus pneumoniae (44.8%) was found to be the predominant pathogen isolated followed by Klebsiella pneumoniae (20.8%), Acinetobacter baumannii (13.5%) and Staphylococcus aureus (8.3%). The highest resistance was observed with piperacillin, ampicillin, erythromycin, cefaclor, azithromycin. Streptococcus pneumonia isolated were mostly resistant to azithromycin, cefaclor, and erythromycin (85.7%), while 0% resistance was observed for vancomycin, ampicillin and gentamycin. Klebsiella pneumoniae were highly resistant to ampicillin (95%), trimeth/sulfa (85%), and piperacillin (85%). Acinetobacter baumannii had a resistant rate of over 50% to most antibiotics, especially gentamycin and meropenem (84.6%). Staphylococcus aureus were completely resistant to ampicillin, clindamycin, penicillin, while vancomycin resistance was observed among 12.5% of the isolated bacteria. Conclusions: The most common pathogen was Streptococcus pneumoniae, Klebsiella pneumoniae, Acinetobacter baumannii and Staphylococcus aureus. The highest resistance was observed with piperacillin, ampicillin, erythromycin, cefaclor, and azithromycin. Streptococcus pneumoniae was highly resistant to macrolides. Klebsiella pneumoniae was highly resistant to most antibiotics of the 2nd, 3rd generation cephalosporins and beta lactams (penicillin and monobactam). Acinetobacter baumannii showed a noticeable resistance to fluoroquinolones, aminoglycosides, and 4th generation cephalosporins. Staphylococcus aureus was highly resistant to penicillin, lincosamides, fluoroquinolone, while 12.5% vancomycin resistance was observed.

37-Year-Old Man With Headache and Nasal Congestion

37-Year-Old Man With Headache and Nasal Congestion

Effects of a Novel Beta Lactam Compound, MC-100093, on the Expression of Glutamate Transporters/Receptors and Ethanol Drinking Behavior of Alcohol-Preferring Rats

Chronic ethanol exposure affects the glutamatergic system in several brain reward regions including the nucleus accumbens (NAc). Our laboratory has shown that chronic exposure to ethanol reduced the expression of glutamate transporter 1 (GLT-1) and cystine/glutamate exchanger (xCT) and, as a result, increased extracellular glutamate concentrations in the NAc of alcohol-preferring (P) rats. Moreover, previous studies from our laboratory reported that chronic ethanol intake altered the expression of certain metabotropic glutamate receptors in the brain. In addition to central effects, chronic ethanol consumption induced liver injury, which is associated with steatohepatitis. In the present study, we investigated the effects of chronic ethanol consumption in the brain and liver. Male P rats had access to a free choice of ethanol and water bottles for five weeks. Chronic ethanol consumption reduced GLT-1 and xCT expression in the NAc shell but not in the NAc core. Furthermore, chronic ethanol consumption increased fat droplet content as well as peroxisome proliferator-activated receptor alpha (PPAR-α) and GLT-1 expression in the liver. Importantly, treatment with the novel beta-lactam compound, MC-100093, reduced ethanol drinking behavior and normalized the levels of GLT-1 and xCT expression in the NAc shell as well as normalized GLT-1 and PPAR-α expression in the liver. In addition, MC-100093 attenuated ethanol-induced increases in fat droplet content in the liver. These findings suggest that MC-100093 may be a potential lead compound to attenuate ethanol-induced dysfunction in the glutamatergic system and liver injury. SIGNIFICANCE STATEMENT: This study identified a novel beta-lactam, MC-100093, that has demonstrated upregulatory effects on GLT-1. MC-100093 reduced ethanol drinking behavior and normalized levels of GLT-1 and xCT expression in the NAc shell as well as normalized GLT-1 and PPAR-α expression in the liver. In addition, MC-100093 attenuated ethanol-induced increases in fat droplet content in the liver.