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Amoxicillin and cotrimoxazole are among the most frequently prescribed antibiotics, yet their impact on gut microbiota and systemic physiology, particularly during early life, remains a critical concern. This study investigated the effects of these antibiotics on the gut microbiome and associated physiological and biochemical responses in young male Swiss mice (5 weeks old), serving as a model for infant exposure. Five experimental groups were employed: control, amoxicillin (9.62 mg/kg), cotrimoxazole (15 mg/kg), cotrimoxazole + amoxicillin, and cotrimoxazole + amoxicillin followed by probiotic administration. Parameters assessed included gut microbial composition, hematological indices, organ weights, liver and kidney function, cytokine profiles, oxidative stress markers, and histopathological alterations. Both antibiotics induced marked gut dysbiosis. Cotrimoxazole significantly increased leukocyte, neutrophil, lymphocyte, and monocyte counts, while amoxicillin caused thrombocytosis and cotrimoxazole induced thrombocytopenia; probiotic treatment normalized these effects. Amoxicillin reduced brain glutathione (GSH) levels, whereas cotrimoxazole decreased GSH in both liver and brain. Combined antibiotic exposure exacerbated GSH depletion and elevated nitric oxide (NO) and malondialdehyde (MDA) levels, effects mitigated by probiotics exposure. Co-exposure to cotrimoxazole and amoxicillin upregulated pro-inflammatory cytokines TNF-α and IFN-γ and increased serum markers of hepatic and renal injury (alanine-transaminases, alkaline phosphatases, Aspartate transaminases, creatinine, urea, uric acid). Histopathological analysis confirmed aggravated hepatic and renal damage under combined antibiotic exposure, which was markedly alleviated by probiotics. These findings demonstrate that amoxicillin and cotrimoxazole disrupt gut microbial balance, eliciting systemic oxidative, organ damage and inflammatory responses. Probiotic intervention confers significant protection, underscoring the need for cautious antibiotic use and microbiota-restorative strategies.

IntroductionInfection and systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. We aimed to characterise a subset of patients from the ATTIRE study who had infection at baseline presentation. (ATTIRE: Randomised Controlled Trial of Albumin infusions versus standard care in hospitalised patients with cirrhosis, DOI: 10.1056/NEJMoa2022166).MethodsPatients recruited to ATTIRE were analysed retrospectively. Multivariable analysis with binary logistic regression was used to identify factors affecting mortality in patients with evidence of initial infection at presentation. (Criteria for the diagnosis of initial infection can be found in the main ATTIRE trial paper referenced above).A subset of patients had available biomarker data, which were evaluated using ROC analysis to assess their performance in detecting infection.ResultsBaseline infection was present in 211/775 (27%) patients, and was associated with older age (age 55 years vs 53 years, p = 0.035). The presence of infection at baseline predicted mortality independently of age and MELD at: 14 days (OR 2.1, 95% CI 1.3–3.7, p = 0.006), 28 days (OR 1.6, 95% CI 1.1–2.6, p 0.028), 90 days (OR 1.8 95% CI 1.2–2.7, p <0.001) and 180 days (OR 1.5, 95% CI 1.05–2.1, p = 0.026). Antibiotics given at presentation did not confer any survival advantage at 14/28/90 days in patients with or without baseline infection.High LBP/low CD163 were associated with baseline infection in a smaller (n = 134) biomarker-subset (p=0.002/p= 0.03) (with high PCT nearing significance, p = 0.054). However, AUCs for these biomarkers for the prediction of baseline infection were all < 0.7.Of the 211 patients with baseline infection, co-occurring renal dysfunction in the first 14 days was the greatest predictor of 90-day mortality (OR 7.87 95% CI 3.07–20.2, p<0.001).Abstract P58 Figure 1Predictors of mortality in a) the whole ATTIRE cohort (n = 775) at 14 days, b) the whole ATTIRE cohort (n= 775) at 90 days, c) a subset of the ATTIRE cohort (n = 211) with baseline infection, at 90 days[Figure omitted. See PDF]DiscussionIn this cohort of patients presenting to hospital with decompensated cirrhosis, evidence of infection at presentation predicted mortality at 90-days, independently from MELD and age, with no survival benefit conferred from antibiotics in the absence of baseline infection.In such a high-risk group of patients, these results highlight the need to focus on the prevention of infection before decompensation occurs. The use of prophylactic antibiotics in patients with ascites is currently being evaluated in the ASEPTIC RCT (co-trimoxazole versus placebo in cirrhotic patients with ascites).

The present study was aimed to develop an effective probiotic lactic acid bacteria (LAB) from piglet feces and in vitro characterization of probiotic properties. To confirm host-species specificity of probiotics, the efficacy of isolated LAB on growth, nutrient utilization, health and antioxidant status was observed in early weaned piglets. A total of 30 LAB were isolated from feces of five healthy piglets (28d old). All isolates were Gram positive, cocco-bacilli and catalase negative. Out of thirty LAB isolates, twenty were shortlisted on the basis of their tolerance to pH (3.0, 4.0, 7.0 and 8.0) and bile salts (0.075, 0.15, 0.3 and 1.0%). Whereas, fourteen isolates were selected for further in vitro probiotic characterization due higher (P<0.05) cell surface hydrophobicity to toluene (>45 percent). These isolates fermented twenty-seven different carbohydrates but were negative for ONPG, citrate and malonate. Also enabled to synthesize amylase, protease, lipase and phytase. They were sensitive to penicillin, azithromycin, lincomycin, clindamycin, erythromycin, cephalothin and chloramphenicol and resistant to ciprofloxacin, ofloxacin, gatifloxacin, vancomycin and co-trimoxazole. Except three isolates, all showed antagonistic activity (>60% co-culture activity) against Escherichia coli, Salmonella Enteritidis, Salmonella serotype (ser.) Typhimurium, Staphylococcus intermedius, Staph. chromogenes, Proteus mirabillis, Areomonas veonii, Bordetella bronchioseptica and Klebsialla oxytoca. The isolate Lacp28 exhibited highest tolerance to acidic pH and bile salts (up to 0.3%), phytase activity, cell surface hydrophobicity, antagonistic activity and co-culture assay (>80% growth inhibition). Host specificity of Lacp28 was further confirmed by heavy in vitro adhesion to pig intestinal epithelium cells compared to chicken. Hence, Lacp28 was selected and identified by phylogenetic analysis of 16S rRNA as Pediococcus acidilactici strain FT28 with 100% similarity (GenBank accession nos. KU837245, KU837246 and KU837247). The Pediococcus acidilactici FT28 was selected as potential probiotic candidature for in vivo efficacy in weaned pigs. Thirty-six crossbred piglets (28d) were randomly distributed into three groups (four replicates of three each) namely, basal diet without probiotics (T0) or with Lactobacillus acidophilus NCDC15 (conventional dairy-specific probiotic; T1) or Pediococcus acidilactici FT28 (swine-specific probiotic; T2). At end of the experiment, six piglets of similar body weight were selected to conduct digestion trial for estimation of nutrient digestibility. Results of the study indicated that supplementation of both probiotics improved (P<0.001) FCR compared to control without significant effect in average daily gain and DM intake. However, the apparent digestibility of crude protein and ether extract was better (P<0.01) in pigs fed P. acidilactici FT28 compared control and L. acidophilus fed groups. The total WBC and RBC count, serum glucose, total protein, albumin and globulin concentration was higher (P<0.05) in P. acidilactici FT28 fed group with better (P<0.05) catalase and superoxide dismutase activity measured in erythrocyte. It is concluded that species-specific Pediococcus acidilactici FT28 isolated with potential in vitro probiotic properties and also hold probiotic candidature by showing the potential capabilities with higher nutrient digestibility, heamato-biochemical and antioxidant status compared to control and Lactobacillus acidophilus NCDC15.

IntroductionRecurrent ascites is a recognised complication of advanced liver disease, with many patients requiring repeated elective paracentesis. This can be performed by a day case unit. SBP occurs in 1.5–3.5% of outpatients and 10% of inpatients with ascites.1 SBP in an elective setting differs from acute hospitalisations without a good evidence base, leading to varied management.AimTo report outcomes in all patients diagnosed with SBP from our elective paracentesis service over a 3 year period. Primary outcomes were overall and 30-day mortality. Secondary outcomes were readmission rates and total inpatient days (LoS).MethodsThis is a retrospective, single-centre, audit of total ascitic white cells (WCC) arising from 1576 elective paracenteses performed January 2021 - December 2023. SBP was defined as ascitic WCC ≥ 0.5 x109/L. Paracenteses for non-cirrhotic causes were excluded.Results62 instances of SBP occurred in 1576 drains (3.93%), corresponding to 39 episodes in 33 patients. Median age was 60. 24 (72.7%) were male. 19 (57.6%) had alcohol-related cirrhosis, 10 (30.3%) metabolic, 3 (9.1%) mixed and 1 (3%) autoimmune hepatitis. Median UKELD was 55. Mean ascitic WCC was 1.68 x109/L. 26 (66.7%) had never had SBP, 9 (23.1%) had 1, 3 (7.7%) had 2 and 1 (2.6%) had 3 prior SBP episodes. 23 (60%) had no SBP prophylaxis, 11 (28.2%) Co-trimoxazole and 5 (12.8%) Ciprofloxacin. 24 (61.5%) were on proton pump inhibitors. 15 (38.4%) were on non-selective beta blockers. 15 (45.5%) are deceased, 4 (12.1%) transplanted and 18 (54.5%) alive.Of 39 SBP episodes, 27 (69.2%) were treated as inpatients, 11 (29.7%) as ambulatory and 1 excluded due to prior admission. Of those directly admitted, 1 (3.7%) required further inpatient treatment compared with 6 (54.5%) of those ambulatory. In those admitted, mean total LoS was 7.4 days vs 5.8 days in those ambulatory. Table 1 compares patient characteristics:Abstract P367 Table 1 Admitted Ambulatory Frequency 27 11 Age (median) 59 64.5 Overall mortality 10 (40%) 4 (40%) 30-day mortality 2 (8%) 2 (20%) Ascitic WCC (x109/L) 1.76 1.5 Sodium 132 134.3 Creatinine 86.6 102.1 Bilirubin 47.1 20 Albumin 31.9 28.8 Prothrombin Time 14.1 12.5 CRP 47.8 15 Acute Kidney Injury 5 (19.2%) 3 (37.5%) ConclusionIn elective patients diagnosed with SBP, direct admission reduced readmission rates but increased total LoS. Overall mortality was no different. With elective paracentesis units, a new evidence base and algorithm should be developed, and may identify a sub-group of patients that could be safely managed as ambulatory with reassessment after a course of antibiotics.ReferenceAithal GP, Palaniyappan N, China L, et al. Guidelines on the management of ascites and cirrhosis. Gut. 2021;Jan;70(1):9–29.

Antibiotic resistance is a global health crisis that requires urgent action to stop its spread. To counteract the spread of antibiotic resistance, we must improve our understanding of the origin and spread of resistant bacteria in both community and healthcare settings. Unfortunately, little attention is being given to contain the spread of antibiotic resistance in community settings (i.e., locations outside of a hospital inpatient, acute care setting, or a hospital clinic setting), despite some studies have consistently reported a high prevalence of antibiotic resistance in the community settings. This study aimed to investigate the prevalence of antibiotic resistance in commensal Escherichia coli isolates from healthy humans in community settings in LMICs. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we synthesized studies conducted from 1989 to May 2020. A total of 9363 articles were obtained from the search and prevalence data were extracted from 33 articles and pooled together. This gave a pooled prevalence of antibiotic resistance (top ten antibiotics commonly prescribed in LMICs) in commensal  E. coli  isolates from human sources in community settings in LMICs of: ampicillin (72% of 13,531 isolates, 95% CI: 65–79), cefotaxime (27% of 6700 isolates, 95% CI: 12–44), chloramphenicol (45% of 7012 isolates, 95% CI: 35–53), ciprofloxacin (17% of 10,618 isolates, 95% CI: 11–25), co-trimoxazole (63% of 10,561 isolates, 95% CI: 52–73), nalidixic acid (30% of 9819 isolates, 95% CI: 21–40), oxytetracycline (78% of 1451 isolates, 95% CI: 65–88), streptomycin (58% of 3831 isolates, 95% CI: 44–72), tetracycline (67% of 11,847 isolates, 95% CI: 59–74), and trimethoprim (67% of 3265 isolates, 95% CI: 59–75). Here, we provided an appraisal of the evidence of the high prevalence of antibiotic resistance by commensal  E. coli  in community settings in LMICs. Our findings will have important ramifications for public health policy design to contain the spread of antibiotic resistance in community settings. Indeed, commensal  E. coli is the main reservoir for spreading antibiotic resistance to other pathogenic enteric bacteria via mobile genetic elements.

Background Escherichia coli has found to be the predominant uropathogen (50–90%) in uncomplicated, community acquired urinary tract infection (UTI). Uropathogenic Escherichia coli (UPEC) express a multitude of virulence factors, which enable the bacteria to establish UTI. The objective of this study was to evaluate the presence of different phenotypic virulence markers in UPEC isolates and determine their correlation with antibiotic resistance pattern. Results Out of 105 patients, 56 (53%) were females and 49 (47%) were males. The age of the patients in the study ranged from 18 years to 87 years and majority of the patients belonged to the age group 20–29 years. Virulence factor was observed in 65% (n = 69) of UPEC and 20% (n = 22) of control isolates (P = 0.0001). Haemolysin production was observed in 34(32.3%) of uroisolates and 12 (11.4%) of control strain. Similarly, 62% of UPEC and 1% of control produced biofilm (P = 0.0001). The expression of Mannose-resistant hemagglutinin (MRHA) and mannose-sensitive hemagglutinin (MSHA) in uroisolates were 52.3% (n = 55) and 5.7% (n = 6) respectively, whereas in faecal isolates, 8.5% (n = 9) expressed MRHA and none produced MSHA. Antimicrobial resistance showed a high degree of resistance towards ampicillin, cotrimoxazole and norfloxacin. The resistance was observed in significant higher degree in biofilm formers as compared to non-formers. MDR and ESBL was observed in 51 and 46% of test strains and 9 and 7.6% of control strains (P = 0.0001). Conclusion A significant association between virulence factors of UPEC and antimicrobial resistance in UPEC was present. Routine testing of these factors and co-relation with AMR is recommended. These findings will certainly help understand the pathogenicity and proper management of UTI patients, thus decreasing the improper use of antibiotics.

Pakistan is currently facing the largest outbreak of ceftriaxone-resistant Salmonella enterica serotype Typhi described to date. Here we aimed to report the outbreak investigation done in Hyderabad, Pakistan, and identify disease risk factors. We did an age-matched case-control (1:4) study, in which cases of ceftriaxone-resistant S Typhi were identified from active sentinal sites (three hospitals in Hyderabad, Pakistan), community, and laboratory-based surveillance. Ceftriaxone-resistant S Typhi infection (ie, resistance to ampicillin, chloramphenicol, co-trimoxazole, fluoroquinole, and ceftriaxone) was confirmed using blood culture. Healthy participants (controls) were enrolled for the first 200 people (cases) with ceftriaxone-resistant S Typhi. A structured questionnaire was administered to identify exposures 4 weeks before the illness (cases) or enrolment (controls). Cases were included if written informed consent was provided. Four controls were selected from the same community as the corresponding case, matched on age, being healthy at the time of enrolment, and with no febrile illness in the 4 weeks before enrolment. Samples of drinking water from households and community water sources (ie, hand pumps or taps in common areas outside households) were collected for testing. Conditional logistic regression analysis was used to assess the risk factors for ceftriaxone-resistant S Typhi outbreak in Hyderabad. Between Nov 30, 2016, and Dec 30, 2017, 486 people with ceftriaxone-resistant S Typhi were identified from Hyderabad. Of the 486 cases, 296 (61%) were male and 447 (92%) were aged 15 years or younger. Several factors were significantly associated with acquisition of ceftriaxone-resistant S Typhi, including male sex (adjusted odds ratio [aOR] 1·53, 95% CI 1·06–2·21), eating outside of the house (aOR 1·48, 1·01–2·19), exposure to a patient with S Typhi infection (aOR 3·81, 2·21–6·83), and a history of antimicrobial use (aOR 4·25, 2·53–7·13). Nine (69%) of 13 water samples taken from the households of people with ceftriaxone-resistant S Typhi infection were positive for Escherichia coli, indicating faecal contamination. S Typhi DNA was detected in 12 (22%) of 55 water samples from community water sources. Geospatial mapping showed clustering of cases around sewerage lines. Hyderabad faces the largest reported outbreak of ceftriaxone-resistant S Typhi. The outbreak is suspected to be attributed to the contaminated drinking water, especially the mixing of sewage with drinking water. The risk of ceftriaxone-resistant S Typhi infection is increased among children aged 15 years and younger, male individuals, and those eating outside the house. Vaccination and chlorination of water are recommended for the containment of the outbreak. None.

Since other similar trials have not enrolled patients infected with carbapenem-resistant A baumannii, it seems unfair to compare cefiderocol's high mortality numbers with those of trials with newer β-lactam–β-lactamase inhibitors.7,8 The small number of patients infected with carbapenem-resistant A baumannii in APEKS-NP (ie, 31 patients) precludes this study's ability to shed any further insight into cefiderocol's efficacy for these challenging pathogens. [...]although trials comparing cefiderocol with worthy comparator regimens for MBL-producing Enterobacterales have not been done, there were no concerning clinical signals when cefiderocol was used in CREDIBLE-CR for such infections,2 including infections outside the urinary tract. [...]an important gap in coverage with currently available novel antibiotics is options for S maltophilia, particularly as intolerance to co-trimoxazole (trimethoprim–sulfamethoxazole) is common and the efficacy of other drugs has not been well established.

The aim of this survey was to summarize the current antimicrobial practice in febrile neutropenia and the presence of key aspects of antimicrobial stewardship. A questionnaire was sent to 567 centers, and complete responses were obtained from 194 (34.2%). Fluoroquinolone and co-trimoxazole prophylaxis are used in 57.1% and 89.1%, respectively. In 66.4%, the first-line empirical therapy is piperacillin/tazobactam, whereas 10.9% use carbapenems. Empirical combination therapy is used in stable patients without history of resistant pathogens in 37.4%. De-escalation to monotherapy is performed within 3 days in 35.3% and after 10 days in 19.1%. Empirical addition of a glycopeptide is performed when fever persists more than 2–3 days in 60.8%. Empirical escalation to a broader spectrum agent is performed when fever persists more than 3–5 days in 71.4%. In case of positive blood cultures with a susceptible pathogen and uncomplicated presentation, 76.7% of centers de-escalate and 36.6% discontinue before neutrophil recovery. In fever of unknown origin with uncomplicated presentation, 54.1% of centers de-escalate and 49.5% discontinue before neutrophil recovery. Recommendations put forward in the ECIL guidelines are not widely implemented in clinical practice. Specific problems include overuse of carbapenems and combination therapy and unjustified addition of glycopeptides without further de-escalation or discontinuation.

Repeated symptomatic urinary tract infections (UTIs) affect 25% of people who use clean intermittent self-catheterisation (CISC) to empty their bladder. We aimed to determine the benefits, harms, and cost-effectiveness of continuous low-dose antibiotic prophylaxis for prevention of recurrent UTIs in adult users of CISC. In this randomised, open-label, superiority trial, we enrolled participants from 51 UK National Health Service organisations. These participants were community-dwelling (as opposed to hospital inpatient) users of CISC with recurrent UTIs. We randomly allocated participants (1:1) to receive either antibiotic prophylaxis once daily (prophylaxis group) or no prophylaxis (control group) for 12 months by use of an internet-based system with permuted blocks of variable length. Trial and laboratory staff who assessed outcomes were masked to allocation but participants were aware of their treatment group. The primary outcome was the incidence of symptomatic, antibiotic-treated UTIs over 12 months. Participants who completed at least 6 months of follow-up were assumed to provide a reliable estimate of UTI incidence and were included in the analysis of the primary outcome. Change in antimicrobial resistance of urinary and faecal bacteria was monitored as a secondary outcome. The AnTIC trial is registered at ISRCTN, number 67145101; and EudraCT, number 2013-002556-32. Between Nov 25, 2013, and Jan 29, 2016, we screened 1743 adult users of CISC for eligibility, of whom 404 (23%) participants were enrolled between Nov 26, 2013, and Jan 31, 2016. Of these 404 participants, 203 (50%) were allocated to receive prophylaxis and 201 (50%) to receive no prophylaxis. 1339 participants were excluded before randomisation. The primary analysis included 181 (89%) adults allocated to the prophylaxis group and 180 (90%) adults in the no prophylaxis (control) group. 22 participants in the prophylaxis group and 21 participants in the control group were not included in the primary analysis because they were missing follow-up data before 6 months. The incidence of symptomatic antibiotic-treated UTIs over 12 months was 1·3 cases per person-year (95% CI 1·1–1·6) in the prophylaxis group and 2·6 (2·3–2·9) in the control group, giving an incidence rate ratio of 0·52 (0·44–0·61; p<0·0001), indicating a 48% reduction in UTI frequency after treatment with prophylaxis. Use of prophylaxis was well tolerated: we recorded 22 minor adverse events in the prophylaxis group related to antibiotic prophylaxis during the study, predominantly gastrointestinal disturbance (six participants), skin rash (six participants), and candidal infection (four participants). However, resistance against the antibiotics used for UTI treatment was more frequent in urinary isolates from the prophylaxis group than in those from the control group at 9–12 months of trial participation (nitrofurantoin 12 [24%] of 51 participants from the prophylaxis group vs six [9%] of 64 participants from the control group with at least one isolate; p=0·038), trimethoprim (34 [67%] of 51 vs 21 [33%] of 64; p=0·0003), and co-trimoxazole (26 [53%] of 49 vs 15 [24%] of 62; p=0·002). Continuous antibiotic prophylaxis is effective in reducing UTI frequency in CISC users with recurrent UTIs, and it is well tolerated in these individuals. However, increased resistance of urinary bacteria is a concern that requires surveillance if prophylaxis is started. UK National Institute for Health Research.