Ampicillin-Sulbactam-Induced Liver Injury in a Pediatric Patient
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SUBMITTER: Fowler C
PROVIDER: S-EPMC10715387 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundAmpicillin/sulbactam (ABPC/ SBT) is one of the most common β-lactam antibiotics for patients with status epilepticus complicated with aspiration pneumonia. It is known that β-lactam antibiotics such as penicillin aggravate epileptic seizures or status epilepticus. Here, we investigated whether ABPC/SBT aggravates seizures using electroencephalography (EEG) monitoring.Case presentationAn 84-year-old male with status epilepticus who presented with a new onset of clonic seizures mainly of his left side and underwent continuous video EEG was analyzed. He had been suffering from severe ulcerative colitis and infectious enteritis, delirium, atrial fibrillation and deep venous thrombosis. His cerebrospinal fluid analysis was unremarkable. Four days after starting levetiracetam, he had a cluster of seizures with impaired consciousness, consistent with status epilepticus. We started fosphenytoin and phenobarbital. We also administered ABPC/SBT twice a day, ten times in total, for aspiration pneumonia while monitoring the patient. He died twelve days after the seizure onset. We analyzed the number and duration of seizures in two hours before and after starting ABPC/SBT for each administration using EEG with trendgraph. After administration of ABPC/SBT, number of seizures significantly increased from 3.2 ± 4.7 to 7.3 ± 9.7 (mean ± SD, p = 0.047, Wilcoxson's signed-rank test) per 2 h. Duration of seizures showed a tendency of increase from 199 ± 275 to 406 ± 536 s (p = 0.079).ConclusionsIn this elderly male patient with status epilepticus, administration of ABPC/SBT aggravated his seizures. EEG monitoring using a trendgraph is useful for evaluation of seizure severity and for analysis of causative factors.
| S-EPMC11697952 | biostudies-literature
Project description:A 34-year-old man receiving his first dose of ampicillin-sulbactam for osteomyelitis in a hospital setting experienced fatal drug-induced anaphylaxis.
| S-EPMC10510019 | biostudies-literature
Project description:BackgroundIntra-abdominal infections are one of the most common infections encountered by a general surgeon. However, despite this prevalence, standardized guidelines outlining the proper use of antibiotic therapy are poorly defined due to a lack of clinical trials investigating the ideal duration of antibiotic treatment. The aim of this study is to compare the efficacy and safety of a three-day treatment regimen of Ampicillin-Sulbactam to that of a three-day regimen of Ertapenem in patients with localized peritonitis ranging from mild to moderate severity.MethodsThis study is a prospective, multi-center, randomized investigation performed in the Department of General, Emergency, and Transplant Surgery of St. Orsola-Malpighi University Hospital in Bologna, Italy. Discrete data were analyzed using the Chi-squared and Fisher exact tests. Differences between the two study groups were considered statistically significant for p-values less than 0.05.Results71 patients were treated with Ertapenem and 71 patients were treated with Ampicillin-Sulbactam. The two groups were comparable in terms of age and gender as well as the site of abdominal infection. Post-operative infection was identified in 12 patients: 10 with wound infections and 2 with intra-abdominal infections. In the Ertapenem group, 69 of the 71 patients (97%) were treated successfully, while the therapy failed in 2 cases (3%). Therapy failures were more frequent in the Unasyn group, amounting to 10 of 71 cases (p = 0.03).ConclusionAccording to these preliminary findings, the authors conclude that a three-day Ertapenem treatment regimen is the most effective antibiotic therapy for patients with localized intra-abdominal infections ranging from mild to moderate severity.Trial registrationTrial registration: ClinicalTrials.gov: NCT00630513.
| S-EPMC3660242 | biostudies-literature
Project description:BackgroundThe pharmacokinetic variability of ampicillin-sulbactam in adults has not been extensively described, particularly in patients with a reduced renal function (i.e., < 60 mL/min).ObjectiveThis study investigated the population pharmacokinetics of ampicillin and sulbactam in patients with a wide range of renal functions and sought to define dosing approaches that have a high likelihood for optimising drug exposure.MethodsSerial blood samples were collected from 16 adult patients receiving intravenous ampicillin-sulbactam in general wards. Total ampicillin and sulbactam concentrations were measured by chromatographic assay and pharmacokinetic parameters were estimated using Pmetrics®. Monte Carlo simulations were used to evaluate the probability of target attainment (PTA) of free ampicillin and sulbactam concentrations exceeding the minimum inhibitory concentration (MIC) for 60% and 100% of the dosing interval. Fractional target attainment (FTA) was calculated against MIC distributions of common hospital pathogens. A threshold of ≥ 90% and ≥ 95% was used to define both optimal PTA and FTA, respectively.ResultsThe median (range) age, weight, and serum creatinine of the study population was 68 (40-82) years, 62 (40-82) kg, and 1.4 (0.6-6.4) mg/dL, respectively. The pharmacokinetics of ampicillin and sulbactam were best described by a two-compartment model with serum creatinine most closely associated with clearance for both drugs. The estimated ampicillin and sulbactam clearances were 5.58 L/h and 4.79 L/h, respectively, while the volumes of distribution were 12.6 L and 15.36 L, respectively. Approved dosing regimens of ampicillin-sulbactam were sufficient against MICs ≤ 8 and ≤ 4 mg/L, respectively. A 4-h infusion enabled optimal PTA at higher MICs. For both dosing targets, optimal FTAs were obtained against Streptococcus pneumoniae.ConclusionOptimal FTAs were obtained against the susceptible MIC distributions of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Applying a 4-h infusion will enhance PTA and FTA, particularly at higher MICs.
| S-EPMC10085897 | biostudies-literature
Project description:BackgroundThe efficacy and safety of a single dose of ampicillin/sulbactam compared to a single dose of cefuroxime at cord clamp for prevention of post-cesarean infectious morbidity has not been assessed.MethodsWomen scheduled for cesarean delivery were randomized to receive a single dose of either 3 g of ampicillin-sulbactam or 1.5 g of cefuroxime intravenously, after umbilical cord clamping. An evaluation for development of postoperative infections and risk factor analysis was performed.ResultsOne hundred and seventy-six patients (median age 28 yrs, IQR: 24-32) were enrolled in the study during the period July 2004-July 2005. Eighty-five (48.3%) received cefuroxime prophylaxis and 91 (51.7%) ampicillin/sulbactam. Postoperative infection developed in 5 of 86 (5.9%) patients that received cefuroxime compared to 8 of 91 (8.8%) patients that received ampicillin/sulbactam (p=0.6). In univariate analyses 6 or more vaginal examinations prior to the operation (p=0.004), membrane rupture for more than 6 hours (p=0.08) and blood loss greater than 500 ml (p=0.018) were associated with developing a postoperative surgical site infection (SSI). In logistic regression having 6 or more vaginal examinations was the most significant risk factor for a postoperative SSI (OR 6.8, 95% CI: 1.4-33.4, p=0.019). Regular prenatal follow-up was associated with a protective effect (OR 0.04, 95% CI: 0.005-0.36, p=0.004).ConclusionsAmpicillin/sulbactam was as safe and effective as cefuroxime when administered for the prevention of infections following cesarean delivery.Trial registrationClinicaltrials.gov identifier: NCT01138852.
| S-EPMC3009979 | biostudies-literature
Project description:BackgroundLiver injury associated with oxaliplatin (L-OHP)-based chemotherapy can significantly impact the treatment outcomes of patients with colorectal cancer liver metastases, especially when combined with surgery. To date, no definitive biomarker that can predict the risk of liver injury has been identified. This study aimed to investigate whether organoids can be used as tools to predict the risk of liver injury.MethodsWe examined the relationship between the clinical signs of L-OHP-induced liver injury and the responses of patient-derived liver organoids in vitro. Organoids were established from noncancerous liver tissues obtained from 10 patients who underwent L-OHP-based chemotherapy and hepatectomy for colorectal cancer.ResultsOrganoids cultured in a galactose differentiation medium, which can activate the mitochondria of organoids, showed sensitivity to L-OHP cytotoxicity, which was significantly related to clinical liver toxicity induced by L-OHP treatment. Organoids from patients who presented with a high-grade liver injury to the L-OHP regimen showed an obvious increase in mitochondrial superoxide levels and a significant decrease in mitochondrial membrane potential with L-OHP exposure. L-OHP-induced mitochondrial oxidative stress was not observed in the organoids from patients with low-grade liver injury.ConclusionsThese results suggested that L-OHP-induced liver injury may be caused by mitochondrial oxidative damage. Furthermore, patient-derived liver organoids may be used to assess susceptibility to L-OHP-induced liver injury in individual patients.
| S-EPMC10891453 | biostudies-literature
Project description:Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered.
| S-EPMC9690242 | biostudies-literature
Project description:Acinetobacter baumannii is emerging with resistance to polymyxins. In 24-h time-kill experiments, high-dose ampicillin-sulbactam in combination with meropenem and polymyxin B achieved additivity or synergy against 108 CFU/ml of two clinical A. baumannii isolates resistant to all three drugs (maximum reductions, 1.6 and 3.1 logs). In a 14-day hollow-fiber infection model, high-dose ampicillin-sulbactam (8/4 g every 8 h, respectively) in combination with meropenem (2 g every 8 h) and polymyxin B (1.43 mg/kg of body weight every 12 h with loading dose) resulted in rapid (96 h) eradication of A. baumannii.
| S-EPMC5328540 | biostudies-literature
Project description:During the antibiotic crisis, bacteriophages (briefly phages) are increasingly considered as potential antimicrobial pillars for the treatment of infectious diseases. Apart from acquired drug resistance, treatment options are additionally hampered by intrinsic, chromosomal-encoded resistance. For instance, the chromosomal ampC gene encoding for the AmpC-type β-lactamases is typically present in a number of nosocomial pathogens, including S. marcescens. In this study, phage SALSA (vB_SmaP-SALSA), with lytic activity against clinical isolates of S. marcescens, was isolated from effluent. Besides phage characterization, the aim of this study was to evaluate whether a synergistic effect between the antibiotic ampicillin/sulbactam (SAM) and phage can be achieved despite intrinsic drug resistance. Phage SALSA belongs to the Podoviridae family and genome-wide treeing analysis groups this phage within the phylogenetic radiation of T7-like viruses. The genome of Phage SALSA consists of 39,933 bp, which encode for 49 open reading frames. Phage SALSA was able to productively lyse 5 out of 20 clinical isolates (25%). A bacterial challenge with phage alone in liquid medium revealed that an initial strong bacterial decline was followed by bacterial re-growth, indicating the emergence of phage resistance. In contrast, the combination of SAM and phage, together at various concentrations, caused a complete bacterial eradication, confirmed by absorbance measurements and the absence of colony forming units after plating. The data show that it is principally possible to tackle the axiomatic condition of intrinsic drug resistance with a dual antimicrobial approach, which could be extended to other clinically relevant bacteria.
| S-EPMC7400198 | biostudies-literature
Project description:We investigated the epidemiology and resistance mechanisms of ampicillin-sulbactam-nonsusceptible Escherichia coli, focusing on the role of the TEM-1 β-lactamase. We collected all nonduplicate E. coli clinical isolates at 10 Japanese hospitals during December 2014 and examined their antimicrobial susceptibility, β-lactamases, TEM-1 transferability, TEM-1 β-lactamase activity, outer membrane protein profile, membrane permeability, and clonal genotypes. Among the 329 isolates collected, 95 were ampicillin-sulbactam nonsusceptible. Of these ampicillin-sulbactam-nonsusceptible isolates, β-lactamases conferring resistance to sulbactam, such as AmpC, were present in 33%. Hyperproduction of sulbactam-susceptible β-lactamases, TEMs with a strong promoter, were rare (5%). The remaining 59 isolates (62%) had only sulbactam-susceptible β-lactamases, including TEM-1 with a wild-type promoter (n = 28), CTX-Ms (n = 13), or both (n = 17). All 45 transconjugants from 96 donors with TEM-1 had higher ampicillin-sulbactam MICs (4 to 96 mg/liter) than the recipient (2 mg/liter). In donors with only TEM-1, TEM-1 activity correlated with the 50% inhibitory concentration of sulbactam and ampicillin-sulbactam MICs. The decreased membrane permeation of sulbactam was associated with an increased ampicillin-sulbactam MIC. The reduced permeation was partly attributable to deficient outer membrane proteins, which were observed in 57% of the ampicillin-sulbactam-nonsusceptible isolates with only TEM-1 and a wild-type promoter. Sequence type 131 (ST131) was the most common clonal type (52%). TEM-1 with a wild-type promoter primarily contributed to ampicillin-sulbactam nonsusceptibility in E. coli, with the partial support of other mechanisms, such as reduced permeation. Conjugative TEM-1 and the clonal spread of ST131 may contribute to the prevalence of Japanese ampicillin-sulbactam-nonsusceptible isolates.
| S-EPMC6355572 | biostudies-literature