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Probiotics are used to prevent antibiotic-associated diarrhea (AAD) via the restoration of the gut microbiota. However, the precise effects of Akkermansia muciniphila (Akk), which is a promising probiotics, on AAD are unknown. Here, AAD models were established via the administration of lincomycin and ampicillin with or without pasteurized Akk or Amuc_1100 treatment. A diffusion test revealed that Akk was susceptible to the majority of the antibiotics, such as ampicillin. These effects were confirmed by the reduced Akk abundance in AAD model mice. Pasteurized Akk or Amuc_1100 significantly decreased the diarrhea status score and colon injury of AAD model mice. Additionally, these treatments significantly decreased the relative abundance of Citrobacter at genus level and reshaped the metabolic function of gut microbiota. Notably, pasteurized Akk or Amuc_1100 significantly changed the serum metabolome of AAD model mice. In addition, pasteurized Akk or Amuc_1100 suppressed intestinal inflammation by upregulating the expression of GPR109A and SLC5A8 and downregulating the expression of TNFα, IFNγ, IL1β, and IL6. Furthermore, they enhanced water and electrolyte absorption by upregulating AQP4, SLC26A3, and NHE3. Pasteurized Akk or Amuc_1100 also restored intestinal barrier function by ameliorating the downregulation of ZO-1, OCLN, CLDN4, and Muc2 in AAD model mice. In summary, optimizing intestinal health with pasteurized Akk or Amuc_1100 may serve as an approach for preventing AAD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aimed to assess the association between neonatal antibiotic exposure and the risk of childhood obesity., Study Design: This retrospective cohort study enrolled neonates born between 2011 and 2015 and followed up until 5 years. The incidence of obesity at 5 years old, and other characteristics were compared between the antibiotic-exposed and unexposed groups. Chi-square test was conducted on categorical variables and Student's t -test for normally distributed continuous variable. Significant variables ( p  < 0.05) in bivariate analysis were modelled in a stepwise multivariate logistic regression analysis to ascertain independent predictors of obesity at 5 years., Results: Of the 1,447 subjects, 749 (51.8%) received ampicillin and gentamicin, and 333 (23%) were obese. Neonates exposed to antibiotics were more likely to be obese compared with those unexposed (26 vs. 20%, p  = 0.01). In the adjusted model, this association persisted (adjusted odds ratio: 1.37, p  = 0.02)., Conclusion: Neonatal antibiotic exposure is associated with early childhood obesity and may play a significant role in the weight trajectories of these children. Hence, antibiotic stewardship in this period cannot be overemphasized., Key Points: · Findings from our study showed that neonatal antibiotic exposure is associated with early childhood obesity.. · The prevalence of childhood obesity at 5 years is high (23%).. · Further exploration of the role of antibiotics on the gut microbiome and its effect on weight trajectories is needed.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Epstein-Barr virus (EBV) infection frequently develops in children undergoing liver transplantation (LT) because of mandated immunosuppressive therapy. There is a risk of ampicillin rash when penicillin derivatives are used in patients with EBV-associated infectious mononucleosis. Hence, the administration of penicillin derivatives may raise concerns about ampicillin rash in patients with high EBV loads. However, no studies confirmed the risk of administering penicillin derivatives to EBV-infected children after LT., Methods: This retrospective study was conducted at the largest pediatric transplantation center in Japan. We investigated all pediatric liver transplant recipients who received penicillin derivatives within 2 years of LT between 2014 and 2020. We separated the cohort into EBV-positive and EBV-negative groups to assess the frequency of ampicillin and antibiotic-associated rash., Results: Two hundred eighty-six liver transplant recipients were enrolled. There were 111 recipients in the EBV-positive group and 175 recipients in the EBV-negative group. In the EBV-positive group, 49 patients had high EBV DNA loads (≥1000 copies/µg DNA). None of the patients in either group developed ampicillin rash, and the frequency of antibiotic-associated rash did not differ [8/111 (7.2%) vs. 10/175 (5.7%), P = 0.797]. Additional subgroup analysis revealed no difference in the frequency of antibiotic-associated rashes regardless of the presence or absence of high EBV loads., Conclusions: In this study, ampicillin rash was not observed, and antibiotic-associated rash was not associated with concurrent EBV infection. Penicillin derivatives can be used safely, even in liver transplant recipients with persistent asymptomatic EBV infection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Drug-induced liver injury (DILI) is an adverse reaction caused by ampicillin/sulbactam (ABPC/SBT). The albumin-bilirubin (ALBI) score is an index of hepatic functional reserve. However, the relationship between ABPC/SBT-induced DILI and ALBI score remains unknown; therefore, we aimed to elucidate the risk of ABPC/SBT-induced DILI based on the ALBI score., Methods: This was a single-center, retrospective, case-control study using electronic medical records. A total of 380 patients were enrolled in the present study, and the primary outcome was ABPC/SBT-induced DILI. The ALBI score was calculated using serum albumin and total bilirubin levels. In addition, we performed COX regression analysis using age ≥75 years, dose ≥9 g/day, alanine aminotransferase (ALT) ≥21 IU/L, and ALBI score ≥-2.00 as covariates. We also performed 1:1 propensity score matching between non-DILI and DILI groups., Results: The incidence of DILI was 9.5% (36/380). According to COX regression analysis, the adjusted hazard ratio for ABPC/SBT-induced DILI with an ALBI score ≥-2.00 was 2.55 (95% confidence interval: 1.256-5.191, P = 0.010), suggesting that patients with baseline ALBI score ≥-2.00 may be at high risk for ABPC/SBT-induced DILI. However, significant differences were not observed in cumulative risk for DILI between non-DILI and DILI patients regarding an ALBI score ≥-2.00 after propensity score matching (P = 0.146)., Conclusion: These findings suggest that ALBI score may be a simple and potentially useful index for predicting ABPC/SBT-induced DILI. In patients with an ALBI score ≥-2.00, frequent liver function monitoring should be considered to prevent ABPC/SBT-induced DILI., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Antibiotics (ATBx) and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury (ALI) and might be used in combination with ATBx in clinics. However, the impact of ATBx on APAP-induced ALI has rarely been studied., Methods: First, we compared the effects of seven ATBx on APAP-induced ALI. Then, we analysed faecal, serum and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short-chain fatty acids in this process., Results: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin (Amp) instead of other ATBx. Amp exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP-induced ALF, which was proven by faecal microbiota transplantation from ATBx-treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in Amp-treated mice. Gavage with Lactobacillus, especially Lactobacillus rhamnosus, significantly reversed the severer ALF induced by APAP and Amp. Moreover, Lactobacillus supplementation increased butyrate-producing clostridia and lowered butyrate levels in Amp-treated mice. In accordance, butyrate supplementation could also alleviate Amp-aggravated ALI. In addition, inhibition of nuclear factor erythroid 2-related factor 2 counteracted the protective effect of butyrate on aggravated ALI induced by Amp and APAP., Conclusion: Together, this study revealed a potential health impact of Amp that may exacerbate liver damage when co-exposed to excess APAP., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Current guidelines recommend either ampicillin plus ceftriaxone (AC) or amoxicillin/ampicillin plus gentamicin (AG) with an equivalent class IB recommendation in Enterococcus faecalis endocarditis. However, previous observational studies suggest that AC might be favourable in terms of adverse events., Objectives: To investigate whether AC is non-inferior to AG, and if it is associated with less adverse events., Methods: In June 2021, a systematic literature search using the databases PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS was conducted by two independent reviewers. Studies were considered eligible if (P) patients included were ≥ 18 years of age and had IE with E. faecalis, (I) treatment with AC was compared to (C) treatment with AG and (O) outcomes on in-hospital mortality, nephrotoxicity and adverse events requiring drug withdrawal were reported. Odds ratios and 95% confidence intervals were calculated using random-effects models with the Mantel-Haenszel method, the Sidik-Jonkman estimator for τ 2 and the Hartung-Knapp adjustment., Results: Treatment with AC was non-inferior to AG, as depicted by no significant differences in-hospital mortality, 3-month mortality, relapses or treatment failure. Furthermore, AC was associated with a lower prevalence of nephrotoxicity (OR 0.45 [0.26-0.77], p = 0.0182) and drug withdrawal due to adverse events (OR 0.11 [0.03-0.46], p = 0.0160) than AG., Conclusions: Treatment with AC was non-inferior to treatment with AG, and it was associated with a reduced prevalence of nephrotoxicity and drug withdrawal due to adverse events. Thus, combination therapy with AC appears favourable over AG in patients with E. faecalis IE., (© 2021. The Author(s).)

Background and Aims: Many epidemiological studies suggest an association between antibiotic exposure and the development of inflammatory bowel disease [IBD]. However, the majority of these studies are observational and still the question remains, "Does the specific antibiotic administration regimen play a role in the development of colitis?" This study aimed to compare the possible effects of continuous and intermittent antibiotic exposure on the development of colitis using a colitis-susceptible IL-10 knockout [IL-10 -/- ] mouse model., Methods: IL-10-/- mice [C57BL/6] were randomly assigned to a non-antibiotic group, continuous antibiotic group and intermittent antibiotic group, and observed for 30 weeks. The antibiotic cocktail was given via the drinking water. The differential response to antibiotics was assessed., Results: Intermittent antibiotic treatment resulted in severe colitis with early disease onset in IL-10-/- mice. Higher unit colon weight and spleen weight were observed in intermittent antibiotic-treated mice but not in the continuous antibiotic group. Moreover, intermittent antibiotic treatment aggravated epithelial damage and colonic inflammation, mucosal barrier dysfunction and colonic allergic sensitization in IL-10-/- mice, whereas continuous antibiotic treatment ameliorated these symptoms. Male IL-10-/- mice with intermittent antibiotic exposure were more susceptible to colonic inflammation and allergic response than females., Conclusions: In summary, intermittent antibiotic exposure accelerated the development of severe colitis more than continuous antibiotic exposure in IL-10-/- male mice. In addition to the colonic damage and impaired barrier function, stimulation of allergic response may play a role in accelerating the development of colitis in genetically susceptible mice., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Inappropriate use of antibiotics in animal and human plays a role in the emergence and spread of bacteria resistant to antibiotics which threatens human health significantly. Although extensive use of these antibiotics could contribute to the development of drug resistance, information on the knowledge, attitude and practice of antimicrobial resistance and use among animal farm owners/workers in north western Ethiopia is rare. The objective of the present study was to assess knowledge, attitude and practice of animal farm owner/workers towards antibiotic resistance and use in Amhara regional state north western Ethiopia. A cross sectional study was conducted in selected cities of Amhara regional state from January to February, 2020. Data was collected from 91 participants using structured questionnaire and analyzed using SPSSS version 23. The results showed that 96.7% of respondents gave antibiotics to treat their livestock from different sources. Most of the respondents bought their antibiotics from private pharmacies without prescription and the most frequently mentioned antibiotics used to treat animal diseases was tetracycline (76.9%), followed by ampicillin (72.5%). Although, 90.1% of the animal farm owners heard about antibiotics and antibiotic resistance from different sources, they did not know the factors contributing to the transmission of resistant bacteria to humans and the impact of antibiotic resistance on human and animals' health. Using the mean score 4.44 ± 0.15 as the cut-off, half of the animal farm owners/workers had good knowledge about antimicrobial resistance and use. 52.5% of animal farm owners/workers had positive attitudes towards wise antibiotic use and resistance with a mean score of 28.4 ± 0.5. However, 52.75% participants had poor practice with the mean score of practice 4.95 ± 0.17. Better knowledge, positive attitudes and better practices on antibiotic use and resistance were associated with farm owners/workers who engaged in higher education. Although poor awareness on antimicrobial resistance was perceived by 76.9% of respondents as very important factors that contribute to increasing antibiotic resistance, increasing the use of complementary treatments was perceived by the majority of respondents as very important strategies that contribute to reduce antibiotic use and resistance. The current study disclosed that there is low level of awareness among animal farm owners about the correct use of antibiotics and resistance. It is necessary to raise awareness, develop and implement interventions to reduce antimicrobial use and antibiotic resistance in the study area., (© 2021. The Author(s).)

High consumption of irrational fixed-dose combination (FDC) antibiotics may pose a threat of antimicrobial resistance. In India, ampicillin-cloxacillin was the second highest sold FDC antibiotic behind amoxicillin and clavulanic acid. There remain, however, questions about its efficacy and safety and a lack of regulatory approval. We undertook a literature review for ampicillin-cloxacillin to identify available data on the safety and efficacy of its used as FDC. We identified 1071 studies for screening and 81 studies were considered for inclusion. Only 12 studies in English language were accessible full texts for final review. None of the studies identified provided strong evidence that ampicillin-cloxacillin differed in safety or efficacy to other treatments used, and in particular to the component antibiotics used alone. To fully assess the efficacy and safety of ampicillin-cloxacillin and other FDCs, a standardised search format would be required. This should include broad international collaboration, including contacting the relevant regulatory authorities to facilitate a more evidence-based approach to their use., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society..)

Background: Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis., Objectives: To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis., Search Methods: We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs., Selection Criteria: We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections., Data Collection and Analysis: Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up., Main Results: We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors., Authors' Conclusions: Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Rates of perinatal maternal antibiotic use have increased in recent years linked to prophylactic antibiotic use following Caesarean section delivery. This antibiotic use is necessary and beneficial in the short-term; however, long-term consequences on brain and behaviour have not been studied in detail. Here, we endeavoured to determine whether maternal administration of antibiotics during a critical window of development in early life has lasting effects on brain and behaviour in offspring mice. To this end we studied two different antibiotic preparations (single administration of Phenoxymethylpenicillin at 31 mg/kg/day; and a cocktail consisting of, ampicillin 1 mg/mL; vancomycin 0.5 mg/mL; metronidazole 1 mg/mL; ciprofloxacin 0.2 mg/mL and imipenem 0.25 mg/mL). It was observed that early life exposure to maternal antibiotics led to persistent alterations in anxiety, sociability and cognitive behaviours. These effects in general were greater in animals treated with the broad-spectrum antibiotic cocktail compared to a single antibiotic with the exception of deficits in social recognition which were more robustly observed in Penicillin V exposed animals. Given the prevalence of maternal antibiotic use, our findings have potentially significant translational relevance, particularly considering the implications on infant health during this critical period and into later life., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study sought to investigate whether dosing frequency (the number of doses per day) affects the antimicrobial efficacy and safety of ampicillin/sulbactam (ABPC/SBT) in Japanese elderly pneumonia patients treated with ABPC/SBT at 6 g/day. This was a retrospective observational study that included hospitalized elderly patients (aged ≥75 years, 10 ml/min ≤CLcr <50 ml/min) who received 3 g every 12 h (BID; n = 61) or 1.5 g every 6 h (QID; n = 45) for the treatment of pneumonia. The primary endpoint was clinical response, assessed by measuring body temperature, white blood cell count, and C-reactive protein levels. Pharmacokinetic and pharmacodynamic simulations were conducted in silico to rationalize the clinical findings. The clinical response rates (extremely effective and effective) in the BID and QID groups were 36.1% and 55.6%, respectively (p = .0459). QID tended to be more effective in patients with gram-negative rods detected (p = .0563). According to the simulated minimum plasma ABPC concentrations at steady state for BID and QID were 2.5 and 7.3 μg/ml, respectively (p < .0001). Based on the simulated time above minimum inhibitory concentration (MIC), pharmacological (not clinical) efficacy was predicted to be higher with QID. Both groups had similar safety profiles. The main adverse event in both groups was liver damage. The present retrospective survey demonstrated that ABPC/SBT treatment for elderly patients with pneumonia and renal dysfunction was more effective with QID than with BID. Therefore, the QID regimen is worthy of consideration to improve the clinical outcomes of ABPC/SBT therapy in the present patient population., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Background: Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020., Objectives: To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis., Search Methods: We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020., Selection Criteria: Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events., Data Collection and Analysis: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results., Main Results: We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence).  Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better in preventing serious but rare complications.  AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Scope: Soy protein is a high-quality protein and its consumption has been associated with a reduction of serum cholesterol and triglycerides and an improvement in insulin resistance. However, it is not known whether the effects of soy protein are mediated by the gut microbiota. Thus, the aim of this study is to assess whether using antibiotics to partially eradicate the gut microbiota can prevent the beneficial effects of soy protein in rats., Methods and Results: Thus, rats are fed one of the following diets for 16 weeks: casein control, soy protein control, high-fat casein, and high-fat soy protein. The rats are then treated for 4 weeks with antibiotics. Body weight and composition, energy expenditure, glucose tolerance test, metabolic endotoxemia, and gut microbiota are measured before and after treatment with antibiotic. The results show that soy protein consumption decreases weight gain, body fat, metabolic endotoxemia, and increases energy expenditure and glucose tolerance. Antibiotic treatment suppresses all these metabolic effects. These changes are accompanied by modifying the diversity and taxonomy of the gut microbiota., Conclusion: In conclusion, the evidence suggests that the health benefits of soy protein are partly dependent of the gut microbiota., (© 2020 Wiley-VCH GmbH.)

Background & Aims: The enteric nervous system (ENS) exists in close proximity to luminal bacteria. Intestinal microbes regulate ENS development, but little is known about their effects on adult enteric neurons. We investigated whether intestinal bacteria or their products affect the adult ENS via toll-like receptors (TLRs) in mice., Methods: We performed studies with conventional C57/BL6, germ-free C57/BL6, Nestin-creER T2 :tdTomato, Nestin-GFP, and ChAT-cre:tdTomato. Mice were given drinking water with ampicillin or without (controls). Germ-free mice were given drinking water with TLR2 agonist or without (controls). Some mice were given a blocking antibody against TLR2 or a TLR4 inhibitor. We performed whole gut transit, bead latency, and geometric center studies. Feces were collected and analyzed by 16S ribosomal RNA gene sequencing. Longitudinal muscle myenteric plexus (LMMP) tissues were collected, analyzed by immunohistochemistry, and levels of nitric oxide were measured. Cells were isolated from colonic LMMP of Nestin-creER T2 :tdTomato mice and incubated with agonists of TLR2 (receptor for gram-positive bacteria), TLR4 (receptor for gram-negative bacteria), or distilled water (control) and analyzed by flow cytometry., Results: Stool from mice given ampicillin had altered composition of gut microbiota with reduced abundance of gram-positive bacteria and increased abundance of gram-negative bacteria, compared with mice given only water. Mice given ampicillin had reduced colon motility compared with mice given only water, and their colonic LMMP had reduced numbers of nitrergic neurons, reduced neuronal nitric oxide synthase production, and reduced colonic neurogenesis. Numbers of colonic myenteric neurons increased after mice were switched from ampicillin to plain water, with increased markers of neurogenesis. Nestin-positive enteric neural precursor cells expressed TLR2 and TLR4. In cells isolated from the colonic LMMP, incubation with the TLR2 agonist increased the percentage of neurons originating from enteric neural precursor cells to approximately 10%, compared with approximately 0.01% in cells incubated with the TLR4 agonist or distilled water. Mice given an antibody against TLR2 had prolonged whole gut transit times; their colonic LMMP had reduced total neurons and a smaller proportion of nitrergic neurons per ganglion, and reduced markers of neurogenesis compared with mice given saline. Colonic LMMP of mice given the TLR4 inhibitor did not have reduced markers of neurogenesis. Colonic LMMP of germ-free mice given TLR2 agonist had increased neuronal numbers compared with control germ-free mice., Conclusions: In the adult mouse colon, TLR2 promotes colonic neurogenesis, regulated by intestinal bacteria. Our findings indicate that colonic microbiota help maintain the adult ENS via a specific signaling pathway. Pharmacologic and probiotic approaches directed towards specific TLR2 signaling processes might be developed for treatment of colonic motility disorders related to use of antibiotics or other factors., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: Antibiotics play a great role in the treatment of infectious diseases, but meantime, they cause great disturbances to host microbiota. Studies on different antibiotic-induced changes in host microbiota are relatively scarce. This study aimed to investigate the changes in oral and gut microbiota and possible alterations of gut resistance to Salmonella induced by the administration of antibiotics., Methods: The experiment was conducted by administering antibiotics to rats and detecting oral and gut microbiota by 16S rRNA gene sequencing. In second part, after treating with antibiotics or Lactobacillus rhamnosus the rats were infected by Salmonella Typhimurium and the pathogen burden in the gut was counted by colony forming unit assay., Results: The gut microbiota underwent dramatic changes after both vancomycin and ampicillin treatment. The alpha diversity sharply decreased, and the microbiota composition showed a significant difference. However, the gut microbiota recovered within four weeks after stopping antibiotics administration, although this recovery was incomplete. Oral microbiota did not show significant alterations in both alpha and beta diversities. The number of pathogens in the gut in the control group was significantly lower than that in the antibiotic-treated group but only lasted for the first 4 days after infection., Conclusions: Antibiotics cause dramatic alterations in the number and diversity of gut microbiota but not oral microbiota. These changes in the gut microbiota could incompletely recover four weeks later. When infected with pathogens after antibiotic administration, the rats show a decrease in colonization resistance in the gut for the first four days after infection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Vitiligo is impacted by environmental triggers. We studied the contribution of the microbiome in FH mice, in which depigmentation is mediated by tyrosinase-reactive T cells. The mice received oral antibiotics and were monitored for depigmentation. The microbiome was studied in fecal and skin samples using 16S rRNA analysis. The resulting T-cell distributions were evaluated. In untreated mice, pigment loss did not expand to the pelage, whereas mice in the ampicillin group were approximately 1/3 depigmented at 30 weeks. In contrast to models of autoimmunity that are less dependent on IFN-γ, ampicillin but not neomycin treatment correlated with accelerated disease and reduced bacteria in the fecal pellets. Modified cytokine patterns in the tissue and serum suggest a response that transcends the gut. Ampicillin-induced depigmentation was accompanied by gut but not skin dysbiosis, and reduced T cell numbers in both sites. Neomycin induced a redistribution of gut T cells and an accumulation of skin regulatory T cells. This treatment spurred a Bacteroides-dominated population of fecal bacteria. Reduced diversity is prominent particularly after ampicillin treatment, when the gut is dominated by Pseudomonas species. In line with current concepts relating the microbiome and the immune system, we predict that dietary measures might promote skin health and delay vitiligo onset., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Bacterial infection of the urinary tract is among the common reasons for seeking medical attention in the community. Rapidly increasing antibiotic resistance of uropathogens is resulting in limited treatment options. Therefore, knowledge of the current uropathogens and their antibiotic susceptibility is important for better treatment of urinary tract infection., Methods: A cross-sectional study design was conducted from February to September thirty, 2017 among students who came to Mekelle University student's clinics with symptomatic urinary tract infection during the study period.. Mid-stream urine specimens were collected from 341individuals with suspected urinary tract infection for bacteriological identification and antimicrobial susceptibility testing. Data on socio-demographic, clinical and risk factors were also collected using a structured questionnaire., Results: Among the 341 study participants, 72(21.1%) showed significant bacteriuria. Escherichia coli (48.6%), Coagulase-negative staphylococci (23%), Staphylococcus aureus (13.5%), and Klebsiella spp. (8.1%) were common bacterial isolates. Resistance to ampicillin (81-100%), amoxicillin/clavulanic acid (77-93.6%), co- trimoxazole (55 72.3%), nalidixic acid (57.4%) and tetracycline (46-55.5%) was seen by most isolates. Multidrug resistance was observed in 73% of the bacterial isolates, and 25.5% of the Gram-negative isolates were extended-spectrum beta-lactamase producers. Being female, a history of urinary tract infection, a history of catheterization and frequent sexual activity were found to be statistically associated with urinary tract infection., Conclusion: Urinary tract infection is a problem among university students with a prevalence of 21.1%. All isolates have developed resistance to most of the commonly used antibiotics. Therefore, health education on the transmission and causes of urinary tract infection are recommended for the students.

Cross talk between the intestinal microbiome and the lung and its role in lung health remains unknown. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have an impact on the preterm lung. We hypothesized that perinatal antibiotic exposure leads to long-term intestinal dysbiosis and increased alveolar simplification in a murine hyperoxia model. Pregnant C57BL/6 wild type dams and neonatal mice were treated with antibiotics before and/or immediately after delivery. Control mice received phosphate-buffered saline (PBS). Neonatal mice were exposed to 95% oxygen for 4 days or room air. Microbiome analysis was performed using 16S rRNA gene sequencing. Pulmonary alveolarization and vascularization were analyzed at postnatal day (PND) 21. Perinatal antibiotic exposure modified intestinal beta diversity but not alpha diversity in neonatal mice. Neonatal hyperoxia exposure altered intestinal beta diversity and relative abundance of commensal bacteria in antibiotic treated mice. Hyperoxia disrupted pulmonary alveolarization and vascularization at PND 21; however, there were no differences in the degree of lung injury in antibiotic treated mice compared to vehicle treated controls. Our study suggests that exposure to both hyperoxia and antibiotics early in life may cause long-term alterations in the intestinal microbiome, but intestinal dysbiosis may not significantly influence neonatal hyperoxic lung injury.

Antibiotic-associated diarrhea (AAD) is a common adverse effect of antibiotic treatment. The study was to evaluate effects of Chinese yam (Dioscorea opposita Thunb.) on AAD, and changes of intestinal microbiota and short-chain fatty acids (SCFA). AAD model was established using Balb/c mice by gavage with ampicillin for 5 days, followed by a 10-day administration of low, medium, and high dosage of Chinese yam, containing allantoin (4.35 mg/g) and polysaccharides (85.51 mg/g). The results showed that Chinese yam accelerated the recovery from acute diarrhea, reverse AAD-induced body weight loss and cecal enlargement. The high-dosage Chinese yam increased probiotic Bifidobacteria and Lactobacilli by 47% and 21% and decreased potential pathogen Enterococcus and Clostridium perfringens by 8% and 27% on day 15 (P < .05). Bacterial community analysis revealed that Chinese yam contributed to repair the ampicillin-induced intestinal microbiota disorder, enrich the abundance of Bacteroides spp. and Clostridium spp. Additionally, Chinese yam supplementation increased the production of SCFA., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lymphocytic myocarditis is an inflammatory disease of the heart that may present in a myriad of fashions ranging from mild febrile illness to florid myocarditis and cardiogenic shock. Given its nonspecific clinical presentation, the diagnosis of lymphocytic myocarditis is often challenging. The authors describe four cases of lymphocytic myocarditis in young women who presented with cardiogenic shock. Two patients survived and two died. This presentation has not been seen previously in Hawai'i and the public awareness of this condition is critical. Early diagnosis and the prompt initiation of biventricular mechanical circulatory support appear to have been critical in improving patient survival., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Background: Vitamin K deficiency results in serious coagulation dysfunction, but hemorrhagic shock is rare. Herein, we describe a case of vitamin K deficiency and abnormality in the path of the intercostal artery, the combination of which led to hemorrhagic shock., Case Presentation: An 83-year-old woman was hospitalized for suspected gallstones. She developed septic shock after 4 days of hospitalization. We considered cholecystitis or cholangitis and performed abdominal ultrasonography, which revealed gallbladder enlargement, biliary sludge, and hyperplasia of the bile duct wall. Antibiotic treatment with sulbactam/ampicillin (SBT/ABPC) was initiated on day four, and percutaneous transhepatic gallbladder drainage (PTGBD) was performed on day five. The treatment was successful, but the patient developed bilateral pleural effusion because of hypoalbuminemia. We performed drainage for bilateral pleural effusion on days 13 and 17. The patient developed hypotension on day 18; blood tests showed anemia and severe coagulation dysfunction but a normal platelet count. We suspected vitamin K deficiency-induced coagulation dysfunction because of previous antibiotic treatment and restricted diet, and it led to hemorrhagic shock. Massive right hemothorax was observed by computed tomography, and urgent interventional radiology was performed. We observed no injury to the intercostal artery truncus but confirmed an abnormality in the course of the intercostal artery; therefore, we inferred that the cause of hemothorax in this case was injury to a small vessel, not truncus because of the abnormality. Because of the likelihood of rebleeding, we performed coil embolization from the seventh to the ninth intercostal artery. Because we confirmed vitamin K deficiency-induced coagulation dysfunction, we referred to the concentration of protein induced by vitamin K absence/antagonist-II (PIVKA-II), and it was found to increase by 23,000., Conclusions: A combination of vitamin K deficiency and abnormality in the course of the intercostal artery led to hemorrhagic shock. When using certain antibiotics and restricting diet, it is important to measure coagulation function, even if the platelet count is normal. Further, when thoracentesis is performed, abnormalities in the course of the intercostal artery should be identified. Thoracentesis with ultrasound may prevent hemothorax.

The main objective of this work is to investigate the impact of oral administration of ampicillin on the ecological balance of enterococci in the intestinal microbiota of rats during a treatment and a post-treatment. The results have showed that the treated animals excreted significantly higher percentages of resistant enterococci compared to the control group (P ≤ 0.05) during the treatment and after the treatment. The most predominant species selected after the treatment began were Enterococcus faecium. The MICs for ampicillin for all isolates of E. faecium were 32 to 64 µg/mL, with the exception of two strains (TR1LBMB, TR5LBMB), were found to be highly resistant (MICs ≥ 128 µg/mL). Quantification of ampicillin in faeces by the RT-HPLC showed that the significant increase in the number of ampicillin-resistant enterococci was associated with the gradual accumulation of high levels of unabsorbed ampicillin in the faeces. Our results suggest that ampicillin treatment can now be understood as a side effect contributing to the increase in the number of resistant Enterococcus strains, particularly E. faecium strains, recognized as important nosocomial pathogens.

Background: Parameters within reconstitution, storage, stability, and administration may be optimized according to the unique pharmacokinetics of each antibiotic to ensure a successful desensitization., Objective: The study aims to evaluate the successfulness and safety of antibiotic desensitization protocols developed by the pharmacy department at our institution., Methods: A retrospective study was conducted at an 800-bed, urban, tertiary care, academic medical center. A total of 36 patients 18 years of age or older, admitted to our intensive care units between March 2013 and July 2017, who underwent antibiotic desensitization utilizing our pharmacy developed protocols were included., Results: In 36 patients, 61 desensitization cases were identified and included; 17 (47%) were male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In all, 15 different antibiotics were administered for desensitization, with meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7, 11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61 desensitizations were completed successfully with or without experiencing reactions, and 53 (89%) of the successful desensitization cases were completed without reactions. Two cases were categorized as anaphylaxis, which was severe enough to terminate the desensitization process. Of the 59 cases successfully completed, the 6 (10%) cases that experienced reactions were managed successfully during desensitization with completion of the process. Conclusion and Relevance: The findings suggest that our pharmacy-developed antibiotic desensitization protocols are successful and safe and may be adapted by other institutions.

The aim of the present study was to determine whether there is the mechanistic connection between antibacterial-dependent gut microbiota disturbance and anxiety. First, exposure of mice to ampicillin caused anxiety and colitis and increased the population of Proteobacteria, particularly Klebsiella oxytoca, in gut microbiota and fecal and blood lipopolysaccharide levels, while decreasing lactobacilli population including Lactobacillus reuteri. Next, treatments with fecal microbiota of ampicillin-treated mouse (FAP), K. oxytoca, or lipopolysaccharide isolated from K. oxytoca (KL) induced anxiety and colitis in mice and increased blood corticosterone, IL-6, and lipopolysaccharide levels. Moreover, these treatments also increased the recruitment of microglia (Iba1 + ), monocytes (CD11b + /CD45 + ), and dendritic cells (CD11b + /CD11c + ) to the hippocampus, as well as the population of apoptotic neuron cells (caspase-3 + /NeuN + ) in the brain. Furthermore, ampicillin, K. oxytoca, and KL induced NF-κB activation and IL-1β and TNF-α expression in the colon and brain as well as increased gut membrane permeability. Finally, oral administration of L. reuteri alleviated ampicillin-induced anxiety and colitis. These results suggest that ampicillin exposure can cause anxiety through neuro-inflammation which can be induced by monocyte/macrophage-activated gastrointestinal inflammation and elevated Proteobacteria population including K. oxytoca, while treatment with lactobacilli suppresses it.

This article presents the case of a patient with newly developed skin erosions and ulcerations following an exanthematous drug eruption due to sultamicillin therapy. The skin lesions were treated topically with clobetasol and prednicarbate and orally with methylprednisolone. A skin smear revealed massive growth of Escherichia coli bacteria. Blood cultures were negative. The cause for developing ecthyma gangrenosum in our patient were iatrogenic immunosuppression and transient bacteremia.

Although the outcome of flavivirus infection can vary from asymptomatic to lethal, environmental factors modulating disease severity are poorly defined. Here, we observed increased susceptibility of mice to severe West Nile (WNV), Dengue, and Zika virus infections after treatment with oral antibiotics (Abx) that depleted the gut microbiota. Abx treatment impaired the development of optimal T cell responses, with decreased levels of WNV-specific CD8 + T cells associated with increased infection and immunopathology. Abx treatments that resulted in enhanced WNV susceptibility generated changes in the overall structure of the gut bacterial community and in the abundance of specific bacterial taxa. As little as 3 days of treatment with ampicillin was sufficient to alter host immunity and WNV outcome. Our results identify oral Abx therapy as a potential environmental determinant of systemic viral disease, and they raise the possibility that perturbation of the gut microbiota may have deleterious consequences for subsequent flavivirus infections., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

The case deals with an anaphylactoid reaction to intravenous ampicillin/sulbactam resulting in cardiogenic syncope and myocardial damage. Symptoms and ECG modifications promptly disappeared after corticosteroids administration. The Kounis syndrome is an acute coronary syndrome, including coronary spasm, acute myocardial infarction and stent thrombosis, resulting from an anaphylactic or anaphylactoid or allergic or hypersensitivity insult. First described in 1991, it can be caused by a lot of substances, particularly antibiotics. The management should be directed to both the allergic reaction and the myocardial damage. The Kounis syndrome is a not rare disease that every physician should know because of the wideness of triggers and the possible fatal evolution if not promptly recognized.

Introduction: The significant pathogens in acute epiglottitis (AE) are poorly defined in the post Haemophilus influenza type b-vaccine era. Furthermore, there is a lack of clinical evaluations of antibiotic regimens in patients with AE. We aimed to evaluate the effectiveness of empiric intravenous ampicillin in the treatment of patients with AE., Materials & Methods: All patients admitted with AE to the Ear-Nose-Throat Department, Aarhus University Hospital, Denmark, from 2001 to 2015 were included., Results: In total, 103 (51 males) patients were included in the study. The median duration of hospitalization was four days. There was no statistical significant difference between patients initially treated with intravenous ampicillin (n = 83) or other antibiotics (n = 20) (p = .26). The antibiotic regimen was altered during admission in 11% of patients, without significant difference between antibiotic groups (ampicillin 10% vs non-ampicillin 15%, p = .44). Complications potentially related to insufficient antibiotic treatment were observed in four (5%) patients initially treated with ampicillin, but in none of the patients initially treated with antibiotics other than ampicillin (p = 1.00). Throat swab cultures and blood cultures frequently yielded negative results., Conclusions: Intravenous ampicillin is efficient as empiric antibiotic therapy for AE patients, leading to a quick recovery and low complication rates.

Background: Pneumonia is a common and potentially serious illness. Corticosteroids have been suggested for the treatment of different types of infection, however their role in the treatment of pneumonia remains unclear. This is an update of a review published in 2011., Objectives: To assess the efficacy and safety of corticosteroids in the treatment of pneumonia., Search Methods: We searched the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS on 3 March 2017, together with relevant conference proceedings and references of identified trials. We also searched three trials registers for ongoing and unpublished trials., Selection Criteria: We included randomised controlled trials (RCTs) that assessed systemic corticosteroid therapy, given as adjunct to antibiotic treatment, versus placebo or no corticosteroids for adults and children with pneumonia., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Two review authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. We estimated risk ratios (RR) with 95% confidence intervals (CI) and pooled data using the Mantel-Haenszel fixed-effect model when possible., Main Results: We included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification.All trials limited inclusion to inpatients with community-acquired pneumonia (CAP), with or without healthcare-associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials.Corticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate-quality evidence), but not in adults with non-severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non-severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high-quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications.Among children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high-quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure.Hyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid-treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93)., Authors' Conclusions: Corticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non-severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits.

Objective: To report a case of recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis with associated ampicillin-induced myoclonic twitches., Materials and Methods: The patient was investigated using cerebral computed tomography, magnetic resonance imaging, cerebrospinal fluid examination, and electroencephalography. Written informed consent was obtained from the patient for access to clinical files for research purposes and publication., Results: We present a middle-aged woman with two recurrent episodes of aseptic meningitis after treatment with trimethoprim-sulfamethoxazole. Additionally, she developed myoclonic twitches as a rare side effect of ampicillin., Conclusion: Aseptic meningitis is a rare adverse reaction to medications like antibiotics. The pathogenesis of trimethoprim-sulfamethoxazole-induced aseptic meningitis is not yet completely understood, but an immune-mediated hypersensitivity reaction is suspected. If patients with an antibiotic therapy due to a systemic or local infection present with severe headache, not only common diagnosis of a parainfectious headache, but also antibiotic-induced aseptic meningitis should be considered.
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Background & Objectives: Typhoid fever is a major cause of morbidity and mortality in the developing countries including India. Resistance to multiple antimicrobial agents is an emerging global problem that has serious impact on the treatment of disease. There are many factors associated with the emergence of resistance. Most important of them is the acquisition and further transmission and spread of resistance markers among various bacterial species. Therefore, we conducted this study to characterize the resistance plasmids in terms of their transferability and stability among Salmonella enterica serovar Typhi., Methods: Six multidrug-resistant S. Typhi isolates were evaluated for the stability and transfer of resistance markers. The resistance plasmids were also checked for the presence of RepHI1A replicon., Results: All resistance markers were found to be transferred to the recipient through conjugation and transformation, except for nalidixic acid. None of the resistance plasmid was found to harbour RepHI1A replicon and therefore, did not belong to incompatibility group IncHI1. Resistance markers were found to be highly stable in all the isolates during serial passages and storage as stab cultures at different temperatures for different time periods., Interpretation & Conclusions: Resistance markers for chloramphenicol, ampicillin, streptomycin and trimethoprim were transferred through conjugation as well as transformation whereas that for nalidixic acid was not transferred in any of the isolates. Markers for chloramphenicol and streptomycin resistance were found to be most stable during various storage conditions. Presence of small-sized non-IncHI1 resistance plasmids is a matter of concern due to their capability to exist inside the host, thereby increasing the possibility of their transmission and spread among S. Typhi and other bacterial species.

Certain stimuli at the gut barrier may be necessary in early life to establish a proper balance of immune tolerance. We evaluated a compromised barrier in juvenile mice in relation to microbiota and local and systemic immunity. BALB/c mice were treated with a low dose of dextran sulfate sodium (DSS) with or without ampicillin and lipopolysaccharide (LPS) to clarify the importance of microbial antigens and interaction between microbial-associated patterns and toll-like receptors. The barrier breach resulted in increased plasma LPS, which was highest in mice treated simultaneously with ampicillin. Adding LPS in the food reduced its levels in plasma. Regulatory T cells were acutely increased in mesenteric lymph nodes (MLN) and spleen during DSS treatment regardless of simultaneous ampicillin treatment. In contrast, NK T and NK cells decreased in MLN and in spleen. This acute DSS effect was reflected in fold changes of haptoglobin and Il1a in colon, and this was also more pronounced in mice simultaneously treated with ampicillin. On day 1 post-treatment, major upregulations of Ifng, Foxp3, Il1b, Il2, and Il6 genes in colon were only observed in the mice simultaneously treated with ampicillin. A two-fold upregulation of colonic Foxp3 and Il1a was evident 25 days post-treatment. DSS skewed the microbiota in favor of Gram negative phyla. Therefore, increased permeability induced tolerogenic immunity independent of microbiota, and this was enhanced by LPS stimulation.

Background: Drug use in preterm neonates admitted to Neonatal Intensive Care Unit (NICU) has been investigated, so far, in terms of unauthorized or off-label use; very little is known on the use of combinations of different active substances, which is frequently required in this population (prophylaxis of infections, treatment of concomitant diseases). The aim of this study was to describe the most common patterns of drug use in an Italian NICU, focusing on those with nephrotoxic potential., Methods: Medical records of preterm neonates (<37 weeks of gestational age) weighing less than 1,500 g at birth and admitted to an Italian NICU were scrutinized in a 3-year retrospective investigation. Analysis included drug exposure, duration of therapies, co-administration of drugs with potential renal side effects; also daily protein supplement was calculated from parenteral nutrition., Results: A cohort of 159 preterm neonates was selected; 68 were born weighing less than 1,000 g (extremely low birth weight infants, ELBW, Group A), 91 weighed between 1,000 and 1,500 g at birth (Group B). Compared to Group B, neonates of Group A were more likely to receive pharmacological treatments: the most used drugs were antibiotics (especially ampicillin and amikacin, p = .07 and p < .001, respectively), antifungals (especially fluconazole, p < .001), and diuretics (especially furosemide, p < .001). Analysis of co-administration of drugs with potential nephrotoxicity showed ampicillin and amikacin as the most reported combination (94.1% of Group A and 31.9% of Group B), the combination of furosemide with antibacterials (ampicillin or amikacin) was also frequently reported, with average period of combination shorter than 2 days., Conclusions: ELBW infants were exposed to a higher number of drugs compared to other neonates and were more likely to receive associations of drugs with nephrotoxic potential (e.g. furosemide and amikacin), though only for short cycles. Further studies should evaluate the safety profile (especially potential renal side effects) related to most commonly used combinations.

Objective: To provide an extensive review of case reports, epidemiological data, and the underlying mechanism of antibiotic-induced skin rash in patients with concurrent infectious mononucleosis (IM)., Data Sources: A MEDLINE literature search inclusive of the dates 1946 to June 2016 was performed using the search terms anti-bacterial agents and infectious mononucleosis. EMBASE (1980 to June 2016) was searched using the terms mononucleosis and antibiotic agent and drug eruption. References of all relevant articles were reviewed for additional citations and information., Study Selection and Data Extraction: We selected English-language, primary literature, review articles, and mechanistic articles that addressed antibiotic-induced skin rash in patients with concurrent IM. We assessed all case reports available for causality utilizing a modified Naranjo nomogram specifically designed for this subject. We assembled the available epidemiological data into tables to identify trends in incidence rates over the years., Data Synthesis: We identified 17 case reports of antibiotic-associated rash in patients with IM. The median Naranjo score was 6 (range = 1 to 8). The top 3 reported drugs were ampicillin, azithromycin, and amoxicillin. Incidence of this adverse effect was higher in the 1960s (55.6%, 45%, and 33%) than in 2013 (33% and 15%). The mechanism most commonly proposed is a transient virus-mediated immune alteration that sets the stage for loss of antigenic tolerance and the development of a reversible, delayed-type hypersensitivity reaction to the antibiotic., Conclusion: A reassessment of the long-held belief of the high incidence (80%-100%) of antibiotic-induced skin rash in patients with IM seems prudent. Additional studies will be necessary to clarify this issue.

Antibiotics are known to cause severe cutaneous adverse reactions, such as the rare acute generalized exanthematous pustulosis (AGEP). Unlike Stevens-Johnson syndrome or toxic epidermal necrolysis, AGEP is rarely life-threatening. Systemic involvement is not typical, and if present usually coincides with a mild elevation of the hepatic enzymes and a decrease in renal function. Hence, AGEP is known to have a good prognosis and to be life-threatening only in elderly patients or patients with chronic diseases. Herein, we report a case of AGEP in a young healthy male leading to systemic inflammatory response syndrome and to treatment in an intensive care unit after being treated with 5 different antibiotics. Initial symptoms were not indicative for AGEP and the patient's course of disease led promptly to critical cardiorespiratory symptoms and systemic inflammatory response syndrome. We assume that the administration of the 5 different antibiotics resulted in type IV allergy as well as secondary infection with Enterococcus faecium and Staphylococcus aureus, while the underlying periodontitis also contributed to the severity of this case., (© 2017 S. Karger AG, Basel.)

Objective: To evaluate the relationship between ampicillin dosing, exposure, and seizures., Study Design: This was a retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. We used the EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We included all infants 24-41 weeks gestational age, 500-5400 g birth weight, first exposed to ampicillin prior to 25 days postnatal age. Using a 1-compartment pharmacokinetic model and EHR data, we simulated maximum ampicillin concentration at steady state (C maxss, µg/mL) and area under the concentration time curve from 0 to 24 hours (AUC 24, µg*h/dL). Using multivariable logistic regression, we evaluated association between ampicillin dosing, exposure, and seizures as documented in the EHR., Results: We identified 131 723 infants receiving 134 041 courses of ampicillin for 653 506 infant-days of exposure. The median daily dose was 200 mg/kg/d (25th, 75th percentile; 100, 200). Median C maxss and AUC 24 were 256.6 µg/mL (164.3, 291.5) and 2593 µg*h/dL (1917, 3334). On multivariable analysis, dosing was not associated with seizures. However increasing C maxss (OR = 1.10, 95% CI 1.03, 1.17) and AUC 24 (OR 1.11, 95% CI 1.05, 1.18) were associated with increased odds of seizures., Conclusions: In this cohort of hospitalized infants, higher ampicillin exposure was associated with seizures as documented in the EHR., Competing Interests: Individual funding and conflict of interest information are available at www.jpeds.com (Appendix 2)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs.

Unlabelled: Commensal bacteria have been proposed to play a role in liver repair after partial (67%) hepatectomy. However, the underlying immune mechanisms remain elusive. Here, we show that liver regeneration was impaired in antibiotic (Atb) water-treated mice and this impairment strongly correlated with commensal bacterial load. Among the various Atbs used in our cocktail, ampicillin-sensitive commensal bacterial was associated with normal liver regeneration. The number of CD1d-dependent natural killer T (NKT) cells in Atb-treated hepatectomized mice was markedly increased, and these NKT cells were functionally overactivated to produce higher interferon-γ. Deficiency of NKT cells or antibody blockade of the CD1d-NKT interaction increased hepatocyte proliferation, which improved liver regeneration. Importantly, an increased number of Kupffer cells were observed in Atb-treated mice, and these Kupffer cells produced higher interleukin-12, which then functioned to activate hepatic NKT cells. Interleukin-12p40 deficiency or treatment with an anti-interleukin-12 antibody significantly inhibited NKT cell overactivation and recovered liver regeneration in Atb-treated mice., Conclusion: Commensal bacteria play a critical role in maintaining Kupffer cells in a tolerant state, preventing subsequent NKT cell overactivation during liver regeneration. Moreover, our data suggest that long-term Atb use, which can impair the gut microbiota, may influence liver function by retarding liver regeneration., (© 2015 by the American Association for the Study of Liver Diseases.)

We report a rare case of congenital syphilis (CS) presenting as Jarisch-Herxheimer reaction (JHR) at birth. The mother (primigravida) presented in labor and had not received antenatal care. She was given prophylactic ampicillin 2 g i.v. on admission and delivered shortly thereafter. The male infant (2899 g) had normal vital signs, conjunctival congestion, splenohepatomegaly, and maculopapular rash with small blisters over the entire body. Serological tests on the infant and mother confirmed CS. The infant was given i.v. ampicillin for 14 days (50 mg/kg per day until day 3, 100 mg/kg per day thereafter). One hour after the first injection, the infant developed fever (39°C), tachycardia and tachypnea without worsening of rash. Vital signs improved gradually. The rash reduced markedly at postnatal day 1, and disappeared without pigmentation at day 3. This was considered a JHR following ampicillin injection given to the mother before delivery and to the infant after birth., (© 2015 Japan Pediatric Society.)

Although sulbactam/ampicillin (SBT/ABPC) 3 g 4 times daily (QID) is widely used worldwide for patients with moderate to severe community-acquired pneumonia (CAP), the 3 g QID regimen was not available in Japan. In fact, there has been no evidence from a formal clinical study regarding the efficacy and safety of SBT/ABPC 3 g QID in these patients. We report the first results of a multicenter, unblinded, non-comparative, phase 3 study of SBT/ABPC 3 g QID in Japanese adults with moderate to severe CAP. Forty-seven subjects with moderate to severe CAP were enrolled and received SBT/ABPC 3 g QID intravenously for 3-14 days. The clinical responses assessed by the data review committee (DRC) were the primary endpoints. The secondary endpoints included the bacteriological responses assessed by the DRC. The clinical efficacy rate at the test of cure (TOC) was 94.6%. The bacterial eradication rate at TOC was 91.7%. Causative pathogens were isolated from sputum sample taken at baseline in 28 subjects (59.6%). Common causative pathogens included Streptococcus pneumoniae (14 strains), Haemophilus influenzae (9 strains), and Moraxella catarrhalis (8 strains). The clinical efficacy rate and the bacterial eradication rate at TOC of the common pathogens were, respectively, 92.3% and 90.0% in subjects with S. pneumoniae, 83.3% and 75.0% in subjects with H. influenzae, and 87.5% and 87.5% in subjects with M. catarrhalis. All treatment-related adverse events were mild or moderate in severity. SBT/ABPC 3 g QID was well tolerated and demonstrated excellent clinical and bacteriological responses. ClinicalTrials.gov Identifier: NCT01189487., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)