Antibiotic Treatment Protocols Research Articles

Products from Photolysis Reactions of Tetracycline Mediated by Clay and Humic Substance Induce Contrasting Expressions of Target Resistance Genes.

Phototransformation is a key process affecting the fate of many antibiotics in the environment, but little is known about whether their photoproducts exert selective pressure on bacteria by inducing antibiotic resistance genes (ARGs). Here, we examined the expression of tetracycline resistance gene tet(M) of a fluorescent Escherichia coli whole-cell bioreporter influenced by the phototransformation of tetracycline. The presence of suspended smectite clay (montmorillonite or hectorite, 1.75 g/L) or dissolved humic substance (Pahokee Peat humic acid or Pahokee peat fulvic acid, 10 mg C/L) in aqueous solutions markedly facilitated the transformation of tetracycline (initially at 400 μg/L) with half-life shortened by 1.4-2.6 times. Despite the similar phototransformation ratios (80-90%) of the total loaded tetracycline after 60 min irradiation, the decreased ratios of cell fluorescence intensity (which was proportional to the expression amount of ARG tet(M)) were much higher with the two clays (94 and 93%) than with the two humic substances (44 and 69%) when compared to the respective dark controls. As illustrated by mass spectroscopic and chemical analyses, tetracycline was proposed to be mainly transformed to amide (ineffective in inducing ARGs) with the presence of clays by reaction with self-photosensitized singlet oxygen (1O2), while the humic substances might catalyze the production of another two demethylated and/or deaminated compounds (still effective in inducing ARGs) in addition to the amide compound via reaction with triplet excited state dissolved organic matter (3DOM*). As clay minerals and humic substances are important soil constituents and ubiquitously present in surface environments, the observed clay and humic-dependent photooxidation pathways of tetracycline and the differing selective pressures of the associated products highlight the need for monitoring the transformation compounds of antibiotics and provide critical insight into the development of antibiotic treatment protocols.

Gut microbes regulate glomerular filtration rate in health and in a model of chronic kidney disease

Gut microbes have been implicated in varied physiological and pathophysiological processes. In this study, we hypothesized that gut microbes modulate glomerular filtration rate (GFR). Gut microbiota was depleted using a modified antibiotic (ABX) treatment protocol with a mixture of 1g/L ampicillin, 1g/L neomycin, and 0.5 g/L vancomycin (modified from Rakoff-Nahoum et al. 2004). C57BL/6J male and female mice (6-weeks-old) were treated with ABX in drinking water for five weeks. Bacteria reduction with ABX treatment was confirmed by qPCR of fecal samples using pan-bacterial primers (Ct value for Females, F: ctrl 13±0.18 vs ABX 21±0.41; Males, M: 13±0.11 vs ABX 20±0.44, n=8). GFR measurements were performed in conscious and unrestrained mice by transcutaneous detection of fluorescent FITC-sinistrin. The GFR was significantly increased in ABX-treated mice (F: ctrl 1190±14 vs ABX 1638±21, p=0.03; M: ctrl 1020±25 vs ABX 1381±29, p=0.005, n=8). To investigate if the increased GFR was due to the absence of gut microbiota, we measured GFR in germ-free (GF) mice (born and raised without gut microbes), conventional mice (Ctrl, born with gut microbes), and conventionalized GF mice (CGF, born without gut microbes but given a fecal slurry containing gut microbes by oral gavage). GFR was increased in GF mice (F: 1853±32, p=0.003; M: 1308±16, p=0.02) versus both conventional (F: 1217±17; M: 1087±18) and CGF (F: 1326±31, p=0.02; M: 1101±10, p=0.03, n=7-8). GFR was similar in Ctrl and CGF mice. To further investigate if ABX can increase GFR in chronic kidney disease (CKD) when GFR is impaired, GFR was measured in adenine-induced CKD. Adenine (in food pellets) and ABX (in drinking water) treatments were begun simultaneously; adenine decreased GFR in females at weeks 4 and 6, and in males at weeks 2, 4 and 6. In females, mice co-treated with ABX and adenine had increased GFR on week 4 (chow: 1298±11 vs adenine: 853±8, p<0.0001; adenine vs adenine+ABX: 1040±9, p=0.04) but not week 6 (chow: 1238±21 vs adenine: 618±9, p=0.0001; adenine vs adenine+ABX: 881±14, p=0.09, n=7-9). Of note, GFR exhibited no difference between chow vs adenine (data not shown) on week 2. In males, ABX increased GFR on week 2 (chow: 1116±31 vs adenine: 913±47, p=0.002; adenine vs adenine+ABX: 1150±49, p=0.0003) but not week 4 (chow: 1154±38 vs adenine: 732±58, p<0.0001; adenine vs adenine+ABX: 877±81, p=0.37) or 6 (chow: 1157±43 vs adenine: 513±51, p<0.0001; adenine vs adenine+ABX: 591±50, p=0.56, n=7-9). To explore the mechanism by which ABX increase GFR we tested the hypothesis that, in the absence of gut microbes, proximal tubular Na+ reabsorption increases, leading to a reduced Na+ delivery to the macula densa and altering tubuloglomerular feedback (TGF) to increase GFR. To test this, we used the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMPA) to impair Na+ reabsorption and increase Na+ delivery to the macula densa. As seen previously, treatment with ABX increased GFR on week 3 (F: 1430±13, p=0.04; M:1341±9, p=0.01) and week 5 (F: 1857±21, p=0.002, M: 1443±10, p=0.0001) compared to before treatment (F: 1140±10, M: 1090±11, n=8-9). Co-treatment of EMPA and ABX impaired GFR increases on week 3 (F: 1281±18, p=0.9, M: 1201±11, p=0.9) but not week 5 (F: 1650±21, p=0.01; M: 1281±20, p=0.003) when comparing to before the treatment (F: 1199±15; M: 1109±8, n=8-9). In this study, both the absence (GF) and suppression (ABX) of gut microbes increased GFR in healthy females and males. Moreover, ABX partially restored GFR in adenine-induced CKD females and males. These data suggest that gut microbes influence GFR in both health and disease, and that the mechanism may partially involve TGF. AHA Career Development Award (JX) and NIDDK Diabetic Complications Consortium (RRID:SCR_001415m www.diacomp.org, grants DK076169 and DK 115255 (subaward to JLP)) and American Heart Association Established Investigator Award (to JLP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

1290. Impact of Implementing an IV to PO Antibiotic Treatment Protocol for Orthopedic Infections

Abstract Background Oral (PO) regimens have been utilized more frequently for orthopedic infections in place of intravenous (IV) regimens at our center following publication of the OVIVA trial. Given limited published experience of this approach at US medical centers, we reviewed safety and effectiveness outcomes at ours. Methods This was a retrospective, propensity-score matched, cohort study of adult patients hospitalized for orthopedic infections from 9/30/2020 to 4/30/2022. Patients discharged on PO antibiotics were matched to patients discharged on IV antibiotics, using a 1:1 nearest neighbor approach without replacement. Variables expected to be associated with treatment selection and/or outcome were included in the propensity score (Table 1). Primary outcomes were early (60-day) and late (1-year) treatment failure following discharge. Secondary outcomes were incidence of adverse drug events (ADE), readmissions, and ED encounters within 60 days of discharge. Outcomes were assessed through chart review.Table 1:Baseline Characteristics Results Six hundred sixty-four patients were screened and 401 met criteria for inclusion. Of these, 123 PO-treated patients were matched to 123 IV-treated patients. Baseline characteristics were similar in the two groups after matching, although there were differences in microbiological indication, and patients discharged on PO regimens were treated for shorter durations and were more likely to be discharged home (Table 1). There was no significant difference in the proportions of patients on PO vs IV antibiotics experiencing treatment failure at 60 days (14% vs 9%, P = 0.23), treatment failure at 1 year (21% vs 20%, P = 0.75), ADE within 60 days (6% vs 11%, P = 0.16), 60-day readmission (26% vs 33%, P = 0.26), or 60-day ED encounter (11% vs 10%, P = 0.83). Survival analyses identified no significant differences in time-to-event between PO and IV treatment for any of the outcomes assessed (Figure 1).Figure 1:Kaplan-Meier Survival Plots Conclusion There was no appreciable difference in outcomes between patients discharged on PO compared to IV regimens. Quality-improvement interventions to increase prescribing of PO antibiotics for the treatment of orthopedic infections should be encouraged. Disclosures Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support

Multiplex Detection of Antimicrobial Resistance Genes for Rapid Antibiotic Guidance of Urinary Tract Infections

Identification of antimicrobial resistance markers in urinary tract infections could provide a more targeted approach in the diagnosis and treatment of UTIs while reducing overall public health burdens. We describe a molecular assay as a diagnostic tool for antibiotic resistance characterization to promote faster diagnosis of antibiotic regimens compared to standard microbiology techniques. Targeted antibiotic usage for pathogenic infections remains a main goal for effective antibiotic treatment protocols and reducing the overall public health burden. Rapid identification of the pathogen(s) causing the infection and harboring the antibiotic resistance gene is also a main area of exploration for antibiotic appropriation and stewardship. Urinary tract infections are a common clinical disease and reservoir for pathogenic infection and the development of antibiotic resistance, especially in hospital- and community-acquired settings. Standard methods require urine culture, which is time consuming and relies on phenotypic characterization. A genetic diagnostic method is warranted for the rapid molecular characterization of antibiotic resistance genes to reduce inappropriate exposure to antibiotics while improving the overall treatment model for urinary tract infections. The purpose of this study is to demonstrate logical viability for real-time molecular diagnostics for early identification, active surveillance and overall targeted antibiotic stratification that is proposed as an in vitro rapid and comprehensive tool for assessing proper antibiotic stewardship in UTIs. Here, we describe a multiplex real-time fluorescence polymerase chain reaction (PCR) for probe-based detection of the top 24 antibiotic resistance genes with targeted relationships to target molecular drug classes and administered antibiotics. Multiplexed analysis based on molecular features enables rapid testing while shifting the diagnostic detection paradigm from monocentric infections towards polymicrobial infections. We utilized 366 samples from the FDA-CDC Antimicrobial Resistance Isolate Bank to test the efficacy of the assay and propose a model to infer the identity of bacterial isolates. We found that, in addition to a high level of accuracy in predicting bacterial genus classification, the assay was mostly in agreement with CDC-tested genotypic and phenotypic results. This study provides evidence for using genetic diagnostic methods, such as multiplex qPCR, in the rapid identification of antibiotic resistance (ABR) genes for the characterization and treatment of urinary tract infections.

909. Impact of Implementing an IV to PO Antibiotic Treatment Protocol for Orthopedic Infections on Prescribing Habits and Health Utilization Outcomes

Abstract Background The Oral versus Intravenous Antibiotics for Bone and Joint Infection Trial concluded that oral antibiotics administered during the first six weeks of therapy for orthopedic infections were non-inferior to parenteral antibiotics. Previously, we also conducted a retrospective cohort study of patients at our center with an orthopedic infection. Patients transitioned to oral therapy had significantly fewer adverse events and similar incidences of one year treatment failure compared to patients maintained on parenteral vancomycin. Methods To increase use of oral antibiotics for orthopedic infections, we created a protocol for changing IV to PO antibiotics prior to hospital discharge. We evaluated its effect on prescribing practices and healthcare utilization outcomes. Patients with an orthopedic infection were included if they were discharged within the 90-day pre- and post-protocol study periods, had an inpatient Infectious Disease consult, and were initiated on parenteral vancomycin while inpatient. The primary outcome compared the incidence of oral antibiotics prescribed at discharge. Secondary outcomes included incidence of adverse drug reactions, discharge dispositions, hospital length of stay, canceled follow-up appointments, unplanned readmissions, and early treatment failure. Results Fifty patients were included, 22 and 28 patients in the pre- and post-protocol groups, respectively. Twenty-three (82%) patients in the post-protocol group were prescribed oral antibiotics at discharge compared to 8 (36%) patients in the pre-protocol group. Twenty-three (82%) patients in the post-protocol group were discharged home compared to 13 (59%) patients in the pre-protocol group. Of note, 7 (25%) patients in the post-protocol group had early treatment failure compared to 1 (5%) patient in the pre-protocol group, and 8 (29%) patients in the post-protocol group compared to 4 (18%) patients in the pre-protocol group had an unplanned readmission. Conclusion Providing physicians with an oral antibiotic protocol for orthopedic infections significantly increased the number of oral antibiotic prescriptions at hospital discharge, but the higher rates of treatment failure observed after protocol implementation are concerning and warrant further investigation. Disclosures Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support.

Genetically modified bacteriophages creating for the treatment of infections caused by multidrug resistant bacteria (review)

Antibiotic resistance represents an urgent and unresolved issue due to a rapid spread of multidrug-resistance organisms (MDROs). An alternative approach is the medical use of bacteriophages which have selective and lytic activity against specific bacterial strains, in contrast to broad-spectrum antibiotics. Isolation of bacteriophages is a multi-step, tedious, and labour-intensive technique, and physiology of various bacteriophages has been vaguely studied. These drawbacks hamper the flow production of bacteriophage preparations and require a stringent quality control. Here, we review the existing literature on genetically modified bacteriophages, in particular studies which examined efficacy of such bacteriophages for the treatment of multidrug-resistant infections. Genetically modified bacteriophages showed high efficiency in patients with multidrug-resistant infections applied either as a main treatment modality or as an adjuvant therapy added to the antibiotic treatment protocols. The key advantage of genetically modified bacteriophages is broader and higher lytic activity, as they can target antibiotic resistance genes such as efflux pumps, and low immunogenicity which delays their elimination by immune cells. We propose that genetically modified bacteriophages are able to overcome the shortcomings of natural bacteriophages and can be implemented for the prevention and treatment of bacterial infections, in particular those caused by MDROs.

YERSINIA PSEUDOTUBERCULOSIS INFECTION IN LIONS (PANTHERA LEO) AT A ZOOLOGICAL PARK.

Two co-housed 17-yr-old male lions (Panthera leo) and one 15-yr-old female lion in an adjacent enclosure developed acute lethargy, depression, anorexia, and ataxia at a zoological park in central North Carolina, United States. One of the male lions and the female lion were found dead 5 and 4 d after the onset of clinical signs, respectively. The other male lion recovered without any clinical treatment. A third male lion housed with the female lion never developed clinical signs. Postmortem examination, microscopic evaluation, and bacterial culture of the liver from both deceased lions confirmed systemic Yersinia pseudotuberculosis infection. Susceptibility testing revealed resistance to amoxicillin-clavulanic acid and cefazolin. To investigate the extent of the outbreak, qualitative real-time polymerase chain reaction (PCR) for Y. pseudotuberculosis was performed on feces and substrate from 15 enclosures housing nondomestic felids and canids, resulting in a positive sample from one enclosure housing four asymptomatic lions. This enclosure was adjacent to housing of the deceased female lion. Enrofloxacin was administered to all animals in the vicinity at doses of 5 mg/kg in nondomestic felids and 10 mg/kg in nondomestic canids, orally q24h for 14 d. Repeated fecal PCR performed 1 wk after completing the antibiotic treatment protocol found no positive samples. The source of the infection was not identified despite PCR testing of environmental samples from all enclosures in the vicinity, the remains of a prey item fed out prior to the outbreak, and a single dead rodent found on grounds. No further clinical cases have occurred within the following year.

MICROBIOLOGICAL PROFILE AND ANTIMICROBIAL SENSITIVITY PATTERN OF BLOOD CULTURE ISOLATES OF HOSPITALIZED PATIENTS IN A TERTIARY CARE HOSPITAL OF GUWAHATI, ASSAM.

Introduction: Blood stream infections range from self-limiting infections to life threatening sepsis that requires rapid and aggressive antimicrobial treatment. Knowledge about the bacteriological prole and antimicrobial susceptibility patterns in the local unit helps the clinician in rationalizing the empirical treatment protocols and optimizing the duration of therapy. Aims and Objectives of the study: This study was aimed to study the prole of organisms causing bacteremia and understand antibiotic sensitivity patterns at our hospital. 995 blood samples collected over a period of 14 months from clinically suspected cases ofMaterials and Methods: bacteremia were studied. The isolates which agged positive in Bact Alert system were subcultured and were thereby identied and antimicrobial susceptibility performed using VITEK-2 systems. Positive blood cultures were obtained in 25.7% (256 out of 995) ofResults: cases of which Gram-positive bacteria accounted for 35.9% of cases with Staphylococcus aureus predominance; gram negative bacteria accounted for 57.03 % with Klebsiella pneumonia predominance; and 7.03 % were Candida isolates. Antibiotic sensitivity test report showed all gram positive bacteria were sensitive to tigecycline and 75-100% were sensitive to daptomycin, 88-93% to linezolid and 82-97 % to teicoplanin. The prevalence of MRSA and vancomycin resistance was 25 % and 7 %, respectively. The most sensitive drugs for Gram-negative were colistin (82-93%), tigecycline (56-100%), aminoglycosides (58-96%), and carbapenems (52-91%). The present study emphasizes theConclusions: need for continuous scrutiny and surveillance for the most common pathogens isolated in patients with blood stream infections along with antibiotic sensitivity patterns for formulating rationalized antibiotic treatment protocols and infection control strategies for prevention of septicaemia in hospitalized patients.

Investigating the influence of the gut microbiome on diabetic renal disease

BackgroundGut microbiota have been implicated in a large array of pathophysiological processes including obesity and diabetes. In this study, we utilized a diabetic renal disease model with or without oral antibiotic treatment to investigate how gut microbiota alter diabetic renal disease.MethodsGut microbiota biomass was depleted using a modified antibiotic treatment protocol with a mixture of 1g/L ampicillin, 1g/L neomycin, and 0.5 g/L vancomycin (modified from Rakoff‐Nahoum et al. 2004). C57BL/6J male and female mice (6‐week‐old) were randomly assigned to four different groups (n=8 per sex per group): control diet (CD), high‐fat diet (HFD), CD + antibiotics, HFD + antibiotics. The mice were treated with different diets and/or with antibiotics in drinking water for nine weeks. We measured body weight (BW), non‐fasting glucose, insulin, and glomerular filtration rate (GFR). In addition, we performed a glucose tolerance test (GTT), insulin tolerance test (ITT), and blood analysis. Finally, we did H&E staining of the kidney, and analyzed urine Na+.Results1) BW was significantly increased by HFD (vs CD) in both males and females regardless of antibiotic treatment. 2) Non‐fasting glucose showed no difference among these four groups in males and females. 3) Fasting glucose was dramatically elevated by HFD in males but not females (vs CD). For the GTT, both the peak glucose level and area under curve (AUC) were significantly increased in HFD vs CD, regardless of antibiotic treatment or sex. 4) For the ITT, HFD promoted insulin resistance as measured by changes in the AUC in both males and females. For males on a CD, antibiotics improved insulin responsiveness. 5) GFR was increased by HFD vs CD in both males and females, consistent with a HFD‐induced hyperfiltration, as we published previously with this same model (Halperin Kuhns, AJP Renal 2018). Intriguingly, GFR in females was also enhanced by antibiotic treatment on both the CD and HFD (week 9: CD, F: 182±12.7; HFD, F: 290±19.9, p<0.0001; CD + antibiotics, F: 282±12.6; HFD + antibiotics, F: 373±20.1; p=0.0005 CD vs. CD+antibiotics; p=0.01 HF vs. HF+antibiotics). Similarly, GFR in males also increased with antibiotic treatment in CD, but, not HFD (week 9: CD, M: 191±10.0; HFD, M: 385±19.3, p<0.0001; CD + antibiotics, M: 263±10.5; HFD + antibiotics, M: 390±32.7; p=0.04 CD vs. CD+antibiotics; p>0.99 HF vs. HF+antibiotics). Preliminary data using germ‐free (GF) mice, which do not have microbiota, show that GFR was also increased in GF males and females (vs. conventional mice with gut microbes).ConclusionIn this study, depletion of the gut microbiota via antibiotics increased GFR in both males and females on CD. Interestingly, on a HFD, GFR increased with antibiotics in females but not males. These data suggest that gut microbial signals may directly influence renal function; we are now working to confirm these findings and to explore the underlying mechanisms.

Emergence of resistance genes in fecal samples of antibiotic-treated Philippine broilers emphasizes the need to review local farming practices.

The poultry industry is a major contributor to the Philippine economy. Given the rising concerns in antibiotic resistance and food security, farmers need to maximize profit and output while ensuring safe and ecologically sustainable farming practices. This study surveyed antibiotic use in 12 commercial poultry farms in the Philippines. All farms reported the use of medically important antibiotics either for prophylaxis (91.67%), metaphylaxis (100%), and growth promotion (50%). Considering the widespread use of medically important antibiotics, we then investigated the potential contribution of local antibiotic treatment protocols to the emergence of antibiotic resistance genes in the fecal samples of broiler chickens under a controlled experimental setup. Significantly, we observed the emergence of antibiotic resistance genes ( ermB) in fecal samples of antibiotic-treated broilers after 7 days and 21 days in antibiotic-free broilers raised in the same farming environment. These data were corroborated by antibiotic resistance gene profiles of fecal samples from commercial poultry farms. Antibiotic resistance genes ( tetA, tetB, tetU, tetW, qnrB, qnrS) were prevalent in the fecal samples of antibiotic-treated broilers treated with tetracycline and quinolone antibiotics. Therefore, our study provides concrete evidence for the strong correlation between the use of medically important antibiotics in poultry farming and the emergence of antibiotic resistance genes. Antimicrobial resistance is a major contributor to failures in infectious disease treatment strategies in humans and animals. Therefore, the cost-benefit ratio of poorly regulated antibiotic treatment protocols in poultry farming could have a long-term detrimental impact on our economy and public health. Our study suggests the need to review our current policies and practices in using medically important antibiotics in the Philippine poultry industry.

Antibiotic resistance among bacteria isolated from war-wounded patients at the Weapon Traumatology Training Center of the International Committee of the Red Cross from 2016 to 2019: a secondary analysis of WHONET surveillance data

BackgroundA substantial body of evidence has recently emphasized the risks associated with antibiotic resistance (ABR) in conflicts in the Middle East. War-related, and more specifically weapon-related wounds can be an important breeding ground for multidrug resistant (MDR) organisms. However, the majority of available evidence comes from the military literature focused on risks and patterns of ABR in infections from combat-related injuries among military personnel. The overall aim of this study is to contribute to the scarce existing evidence on the burden of ABR among patients, including civilians with war-related wounds in the Middle East, in order to help inform the revision of empirical antibiotic prophylaxis and treatment protocols adopted in these settings. The primary objectives of this study are to: 1) describe the microbiology and the corresponding resistance profiles of the clinically relevant bacteria most commonly isolated from skin, soft tissue and bone biopsies in patients admitted to the WTTC; and 2) describe the association of the identified bacteria and corresponding resistance profiles with sociodemographic and specimen characteristics.MethodsWe retrospectively evaluated the antibiograms of all consecutive, non-duplicate isolates from samples taken from patients admitted to the ICRC WTTC between 2016 and 2019, limited to skin and soft tissue samples and bone biopsies. We collected data on socio-demographic characteristics from patient files and data on specimens from the WHONET database. We ran univariate and multivariable logistic regression models to test the association between bacterial and resistance profiles with sociodemographic and specimen characteristics.ResultsPatients who were admitted with war-related trauma to the ICRC reconstructive surgical project in Tripoli, Lebanon, from 2016 to 2019, presented with high proportion of MDR in the samples taken from skin and soft tissues and bones, particularly Enterobacterales (44.6%), MRSA (44.6%) and P. aeruginosa (7.6%). The multivariable analysis shows that the odds of MDR isolates were higher in Iraqi patients (compared to Syrian patients) and in Enterobacterales isolates (compared to S. aureus isolates).ConclusionsOur findings stress the importance of regularly screening patients who present with complex war-related injuries for colonization with MDR bacteria, and of ensuring an antibiotic-sensitivity testing-guided antimicrobial therapeutic approach.

Biofilm formation and antibiotic susceptibility of Staphylococcus and Bacillus species isolated from human allogeneic skin.

Human skin banks around the world face a serious problem with the high number of allogeneic skins that are discarded and cannot be used for grafting due to persistent bacterial contamination even after antibiotic treatment. The biofilm formation capacity of these microorganisms may contribute to the antibiotic tolerance; however, this is not yet widely discussed in the literature. Thisstudy analyzed bacterial strains isolated from allogeneic human skin samples,which were obtained from a hospital skin bank that had already been discardeddue to microbial contamination. Biofilm formation and susceptibility topenicillin, tetracycline, and gentamicin were evaluated by crystal violetbiomass quantification and determination of the minimum inhibitoryconcentration (MIC), minimum biofilm inhibitory concentration (MBIC), andminimum biofilm eradication concentration (MBEC) by the broth microdilutionmethod with resazurin dye. A total of 216 bacterial strains were evaluated, and204 (94.45%) of them were classified as biofilm formers with varying degrees ofadhesion. MBICs were at least 512 times higher than MICs, and MBECs were atleast 512 times higher than MBICs. Thus, the presence of biofilm in allogeneicskin likely contributes to the inefficiency of the applied treatments as antibiotictolerance is known to be much higher when bacteria are in the biofilmconformation. Thus, antibiotic treatment protocols in skin banks shouldconsider biofilm formation and should include compounds with antibiofilmaction.

Carbapenem stewardship program in a French university children's hospital

IntroductionCarbapenems, last-resort antibiotics, are widely used as first-line treatment in patients carrying extended-spectrum beta-lactamases (ESBL) Enterobacteriaceae, including in a pediatric setting. We aimed to implement an antibiotic stewardship program (ASP) to improve the use of carbapenems. MethodsWe implemented an ASP at the Bordeaux Children's University Hospital with 6-month audits on prescribing practice before and after an intervention (revision of antibiotic treatment protocols, a half-day educational session with feedback of the first study period). The number of carbapenem prescriptions was analyzed and two criteria were used to assess conformity of the indication for carbapenem prescription and conformity of the reassessment. A logistic regression was used to assess the overall compliance of carbapenem prescriptions over the two periods adjusted for ESBL carriage. ResultsA total of 57 patients were included with 37 carbapenem prescriptions before the intervention and 23 after. Overall carbapenem consumption decreased from 0.54 prescriptions per 100 admissions to 0.32 (p = 0.06). Conformity increased during the study for indication (46–87%, p = 0.004) and for reassessment (48–78%, p = 0.04) and was significantly associated with the second study period, after adjustment for ESBL carriage. ConclusionOur intervention contributed to a significant improvement in the compliance to indications for carbapenem indication and in the reassessment of the prescription.

Corticosteroids in tuberculous pericarditis whit severe pericardial effusion to avoid constriction: a retrospective study in HIV-negative population

Abstract The role of corticosteroids in the treatment of tuberculous aetiology pericarditis without human immunodeficiency virus (HIV) is not well defined. Is unclear if associating corticoids to regular antibiotic therapy for tuberculosis, can prevent the progression of a severe pericardial effusion to constrictive pericarditis. Despite that, in countries where tuberculosis is an endemic disease and mostly it's not related to HIV, the use of corticosteroids is a common practice, as a part of a strategy to avoid progression of a severe pericardial effusion to a constrictive pericarditis. Our aim is to describe the clinical course of the patients with severe pericardial effusion of tuberculous aetiology and no echocardiographic sings of constriction, distinguishing those who used corticosteroids from those who didn't. We conducted a retrospective study, analyzing the clinical files of 40 patients treated in one hospital in a 5 years period (2016–2021). All of these patients were diagnosed whit severe pericardial effusion of tuberculous aetiology and no signs of constrictive pericarditis, they all finished their specific antibiotic treatment protocol according national guidelines and had at least 2 years of clinical follow from the time of the diagnosis. We found that the mean age was 54 years, 55% were men and 45% women. The mean follow up was 2.6 years. In all patients pericardial drainage was preformed, 60.5% using closed pericardiocentesis and 39.5% using open surgical techniques. 22 patients (55%) received prednisone that was initiated whit a dose of 1mg/kg daily that was reduced weekly in order to complete a 2 month cycle. The other 18 patients (45%) didn't received corticosteroids. In the prednisone group, 3 patients develop constrictive pericarditis during the time of follow up (13.6% of the prednisone group) while 7 patients of the non-corticosteroids group (38.8%) develop constrictive pericarditis. These retrospective study shows that there is a potential reduction in the progression to constrictive pericarditis whit the use of prednisone in HIV negative patients whit severe pericardial effusion of tuberculous aetiology, we need to perform prospective, controlled, blind and multicenter studies, designed to evidence the real effect of these strategy. Funding Acknowledgement Type of funding sources: None. Cases of contriction in both groups

A nested model for tuberculosis: Combining within-host and between-host processes in a single framework

Tuberculosis (TB) is among the 10 top causes of deaths worldwide, and one-quarter of the world population hosts latent TB pathogens. Therefore, avoiding the emergence of drug-resistant strains has become a central issue in TB control. In this work, we propose a nested model for TB transmission and control, wherein both within-host and between-host dynamics are modeled. We use the model to compare the effects of three types of antibiotic treatment protocols and combinations thereof in an in silico population. For a fixed value of antibiotics clearance rate and relative efficacy against resistant strains, the oscillating intermittent protocol, pure or combined, is the most effective against the sensitive strains. However, this protocol also creates a selective advantage for the resistant strains, returning the worst result in comparison to the other protocols. We suggest that nested models should be further developed, since they might be able to inform decision-makers regarding the optimal TB control protocols to be applied under the specific parameters and other epidemiological factors in different populations.

Antibiotic treatment protocols revisited: the challenges of a conclusive assessment by mathematical modelling.

Hospital-acquired bacterial infections lead to prolonged hospital stays and increased mortality. The problem is exacerbated by antibiotic-resistant strains that delay or impede effective treatment. To ensure successful therapy and to manage antibiotic resistance, treatment protocols that draw on several different antibiotics might be used. This includes the administration of drug cocktails to individual patients (combination therapy) but also the random assignment of drugs to different patients (mixing) and a regular switch in the default drug used in the hospital from drug A to drug B and back (cycling). For more than 20 years, mathematical models have been used to assess the prospects of antibiotic combination therapy, mixing and cycling. But while tendencies in their ranking across studies have emerged, the picture remains surprisingly inconclusive and incomplete. In this article, we review existing modelling studies and demonstrate by means of examples how methodological factors complicate the emergence of a consistent picture. These factors include the choice of the criterion by which the effects of the protocols are compared, the model implementation and its analysis. We thereafter discuss how progress can be made and suggest future modelling directions.

Microbiological and Clinicoepidemiological Profile of a Series of Patients with Infective Endocarditis at a Center in Eastern Nepal

Background The microbiological and clinicoepidemiological profile of infective endocarditis (IE) has undergone significant change over time. The pattern of IE studied at local level provides broader vision in understanding the current scenario of this disease. This study aimed to depict the overall picture of IE and its changing profile by evaluating the microbiological and clinicoepidemiological features in the context of a tertiary care center of eastern Nepal. Methods The descriptive study was conducted from September 2017 to August 2018 among IE patients presenting to B. P. Koirala Institute of Health Sciences, Nepal. Detailed history and clinical manifestations of patients were noted. Microorganisms isolated from the blood culture were processed for identification by standard microbiological methods, and susceptibility testings were done. Each patient was assessed daily during hospital stay. Results Ten definite and 7 possible endocarditis cases were studied. The mean age was 41.4 ± 15.85 (17–70) years with predominance of male (4.7 : 1). Rheumatic heart disease (41.1%) was the most common underlying heart disease observed followed by injection drug user endocarditis (23.5%). All the cases had native valve endocarditis. Aortic valve was the most common valve involved (35.3%) followed by mitral, tricuspid, and pulmonary valves. Blood culture positivity was 53%. Staphylococcus aureus was the major causative agent responsible for 23.5% of the cases followed by Enterococcus faecium, Enterococcus faecalis, and Pseudomonas aeruginosa. Mortality of 2 cases (11.8%) was associated with S. aureus and P. aeruginosa. Majority of patients developed acute kidney injury (35.3%) and congestive cardiac failure (23.5%). Conclusion IE patients in our center exhibited differences from the west in terms of age at presentation and predisposing factors but held similarity in terms of commonly isolated microorganisms. The changing patterns of IE, etiological agents, and their antimicrobial susceptibility observed in this study may be helpful for clinicians in formulating a new empirical antibiotic treatment protocol.

High rates of multi-drug resistant gram-negative organisms associated with surgical site infections in a teaching hospital in Ghana

BackgroundThere is limited data to guide the prevention and management of surgical site infections (SSI) in low- and middle-income countries. We prospectively studied aetiological agents associated with SSI and their corresponding antibiotic susceptibility patterns in a tertiary hospital in Ghana.MethodsAs part of a cohort study carried out at the surgical department of the Korle Bu Teaching Hospital (KBTH) from July 2017 to April 2019, wound swabs were collected from patients diagnosed with SSI. Isolates cultured from the wound swabs were identified by MALDI TOF and susceptibility testing was conducted according to EUCAST 2020 guidelines. Clinical data were monitored prospectively.ResultsOf 4577 patients, 438 developed an SSI and 352 microbial isolates were cultured. Isolates were predominantly Gram negative (286, 81%), a pattern seen for all kinds of surgery and all wound classes. The most common species included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Acinetobacter baumannii. The majority of organisms were multi-drug resistant including 86% of E. coli, 52% of A. baumannii and 86% of K. pneumoniae; and 65% (17/26) of the cefotaxime-resistant K. pneumoniae were extended spectrum β-lactamase producing. One of 139 E. coli, 15 of 49 P. aeruginosa, and 6 of 23 A. baumannii were meropenem resistant, but no clonal pattern was found. There was a 1% (5/428) prevalence of methicillin-resistant S. aureus.ConclusionsThe predominance of Gram-negative organisms and the high level of multi-drug resistance indicate a need to re-evaluate antibiotic prophylaxis and treatment protocols in surgical practice in low- and middle-income countries.

Transient Intestinal Colonization by a Live-Attenuated Oral Cholera Vaccine Induces Protective Immune Responses in Streptomycin-Treated Mice.

Current mouse models for evaluating the efficacy of live oral cholera vaccines (OCVs) have important limitations. Conventionally raised adult mice are resistant to intestinal colonization by Vibrio cholerae, but germfree mice can be colonized and have been used to study OCV immunogenicity. However, germfree animals have impaired immune systems and intestinal physiology; also, live OCVs colonize germfree mice for many months, which does not mimic the clearance kinetics of live OCVs in humans. In this study, we leveraged antibiotic-treated, conventionally raised adult mice to study the effects of transient intestinal colonization by a live OCV V. cholerae strain. In a single-dose vaccination regimen, we found that HaitiV, a live-attenuated OCV candidate, was cleared by streptomycin-treated adult mice within 2 weeks after oral inoculation. This transient colonization elicited far stronger adaptive immune correlates of protection against cholera than did inactivated whole-cell HaitiV. Infant mice from HaitiV-vaccinated dams were also significantly more protected from choleric disease than pups from inactivated-HaitiV-vaccinated dams. Our findings establish the benefits of antibiotic-treated mice for live-OCV studies as well as their limitations and underscore the immunogenicity of HaitiV.IMPORTANCE Oral cholera vaccines (OCVs) are being deployed to combat cholera, but current killed OCVs require multiple doses and show little efficacy in young children. Live OCVs have the potential to overcome these limitations, but small-animal models for testing OCVs have shortcomings. We used an antibiotic treatment protocol for conventional adult mice to study the effects of short-term colonization by a single dose of HaitiV, a live-OCV candidate. Vaccinated mice developed vibriocidal antibodies against V. cholerae and delivered pups that were resistant to cholera, whereas mice vaccinated with inactivated HaitiV did not. These findings demonstrate HaitiV's immunogenicity and suggest that this antibiotic treatment protocol will be useful for evaluating the efficacy of live OCVs.

Rifabutin triple therapy for first‐line and rescue treatment of Helicobacter pylori infection: A systematic review and meta‐analysis

Due to the increasing resistance of Helicobacter pylori, there is a need for novel antibiotic treatment protocols. We aimed to perform a systematic review and meta-analysis in order to determine the effectiveness and safety of rifabutin triple therapy for H.pylori infection. We performed a systematic review of prospective clinical trials with a treatment arm consisting of proton pump inhibitor, amoxicillin, and rifabutin and a meta-analysis of randomized controlled trials (RCTs). Thirty-three prospective studies including 44 datasets were identified. Meta-analysis of four RCTs for rescue treatment found no difference between treatment groups (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.437-1.791, I2 =68.1%, P=0.733). Only one RCT compared rifabutin therapy with control for first-line treatment of H.pylori infection (OR 3.78, 95% CI 2.44-5.87, P<0.0001). Treatment was more likely to be successful in Asian versus non-Asian populations (81.0% vs 72.4%, P=0.001) and when daily amoxicillin dose was ≥3000mg or proton pump inhibitor dose was ≥80mg or treatment duration was 14days (80.6% vs 66.0%, P=0.0001). The overall event rate for adverse effects was 24.8% (729/2937) (95% CI 0.23-0.26), and the pooled OR for adverse effects in the treatment versus control group was 0.93 (95% CI 0.50-1.75) (I2 =79.76, P=0.82). Evidence for the effectiveness of rifabutin for the first-line treatment of H.pylori infection in adults is limited, and studies comparing rifabutin with conventional first-line treatments are lacking.