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Oral antibacterial agents that are active against antimicrobial-resistant bacteria are needed. In this double-dummy, randomized, controlled trial, tebipenem pivoxil hydrobromide (an orally bioavailable carbapenem) was noninferior to intravenous ertapenem for the treatment of complicated urinary tract infection.

The efficacy and safety of antibiotic treatment for uncomplicated acute appendicitis has been established at long-term follow-up with the majority of recurrences shown to occur within the first year. Overall costs of antibiotics are significantly lower compared with appendectomy at short-term follow-up, but long-term durability of these cost savings is unclear. The study objective was to compare the long-term overall costs of antibiotic therapy versus appendectomy in the treatment of uncomplicated acute appendicitis in the APPAC (APPendicitis ACuta) trial at 5 years. This multicentre, non-inferiority randomized clinical trial randomly assigned 530 adult patients with CT-confirmed uncomplicated acute appendicitis to appendectomy or antibiotic treatment at six Finnish hospitals. All major costs during the 5-year follow-up were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis. Between November 2009 and June 2012, 273 patients were randomized to appendectomy and 257 to antibiotics. The overall costs of appendectomy were 1.4 times higher (p<0.001) (€5716; 95% CI: €5510 to €5925) compared with antibiotic therapy (€4171; 95% CI: €3879 to €4463) resulting in cost savings of €1545 per patient (95% CI: €1193 to €1899; p<0.001) in the antibiotic group. At 5 years, the majority (61%, n = 156) of antibiotic group patients did not undergo appendectomy. At 5-year follow-up antibiotic treatment resulted in significantly lower overall costs compared with appendectomy. As the majority of appendicitis recurrences occur within the first year after the initial antibiotic treatment, these results suggest that treating uncomplicated acute appendicitis with antibiotics instead of appendectomy results in lower overall costs even at longer-term follow-up.

Extended‐spectrum beta‐lactamase (ESBL)‐producing Enterobacterales infections are associated with high mortality rates. Ertapenem is recommended as one of the first‐line drugs due to its efficacy against these pathogens. However, physiological changes in critically ill patients may influence drug pharmacokinetics. Thus, this study aims to optimize the ertapenem dosage regimen for critically ill patients in both efficacy and neurotoxicity. The previously reported population pharmacokinetic model and drug‐albumin binding model were used for Monte Carlo simulation. A total of 10 ertapenem dosage regimens were performed in 10,000 simulated critically ill patients with varying degrees of renal function and serum albumin. A PTA of achieving 100% for time of free drug above the minimum inhibitory concentration (fT>MIC) was assessed for efficacy. A PTA of achieving a total drug ≥ 11.77 mg/L was determined for neurotoxicity. A usual recommended dosing of 1 g every 24 h can ensure a PTA > 80% for efficacy only in patients having a creatinine clearance of 30–59 mL/min with unlikely neurotoxic risk (a PTA < 2%). Moreover, the study highlights the need for an individualized ertapenem dosage regimen based on renal function in critically ill patients, as ertapenem in divided doses might be more optimal for both efficacy and safety compared to once daily dosing in patients with creatinine clearance ≥ 60 mL/min. Further randomized controlled trials are needed to confirm these dose recommendations.

The incidence of multi-drug resistant ESBL-associated urinary tract infections (UTIs) is increasing globally. Patients with abnormal renal tract anatomy and other co-morbidities are at increased risk of complicated UTI and ESBL-associated infections. The duration and safety of OPAT for this cohort of patients is unknown. This study aims to provide an evidence base to support decision-making regarding duration of antibiotic treatment for complicated UTIs. We retrospectively reviewed all patients receiving ertapenem with or without adjunctive fosfomycin for complicated UTIs in the OPAT service of our tertiary infectious diseases hospital. All data had been collected prospectively as part of routine clinical care. Our primary outcomes were microbiological and clinical cure of UTI. We identified 33 treatment episodes of ertapenem use for UTIs. 76% episodes related to pyelonephritis or urosepsis diagnoses. Renal tract abnormalities or prior urological surgery were present in 45% of patients. The median duration of appropriate parenteral antibiotic therapy in our study was 6 days. Clinical cure was achieved with short-course parenteral treatment alone in 81% of patients and this increased to 96% when adjunctive fosfomycin was used. There was a single treatment failure resulting in hospital admission. Short duration ertapenem via OPAT with or without adjunctive fosfomycin is safe and effective for the treatment of complicated UTIs. Further studies are required to inform optimal treatment strategies and publication of guidelines in this field.

To evaluate the effectiveness and safety of ertapenem in patients hospitalized at home. Retrospective analysis of data from Spanish Outpatient Parenteral Antimicrobial Therapy (OPAT) registry. Data from 1428 patients (median age 70 years; 5.4% institutionalized) and 1547 infectious processes (24% self-administration) were analyzed. Clinical cure or improvement was achieved in 93.8% of cases. Rate of related readmissions was 4.2%, of clinically important complications -3.9%, and of adverse drug reactions -3.2%. High comorbidity burden, contagion in nursing home and certain types of infection were associated with worse prognosis. Self-administration was effective and safe, except in case of nursing home-acquired infections. Ertapenem OPAT was effective and safe. Caregivers in nursing homes should be better trained in OPAT-related procedures.

Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections and is part of a broader class of antibiotics called carbapenems. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. Previously, a physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose in normal height, normal weight males. Due to the absorption properties of ertapenem, the amount of fat in the body can influence how the drug binds, how quickly the drug passes through the body, and thus how effective the drug might be. Thus, we have revised the model so that it is applicable to males and females of differing body mass index (BMI). Simulations were performed to consider the distribution of the antibiotic in males and females with varying body mass indexes. These results could help to determine if there is a need for altered dosing regimens in the future.

Introduction: In the presence of asymptomatic bacteriuria (ASB) before the urological procedure, the duration of antimicrobial treatment is controversial. This study aims to evaluate whether a short course of antimicrobial therapy is safe and effective in cases with ASB before urological procedures. Methodology: We retrospectively reviewed adult patients who had ASB before undergoing several urological procedures between 2011 and 2019. The patients received a single dose of an appropriate parenteral antibiotic, determined by antimicrobial sensitivity testing, 30 to 60 minutes before the urological procedure. If a urinary catheter was placed post-procedure, a second dose was given. Results: A total of 293 patients who had ASB before undergoing several urological procedures were included in the study. The total number of procedures was 328. Female/male ratio was 92 (31.4%)/201 (68.6%). The mean age was 63.7 ± 14.9 years. The most common isolated microorganisms were Escherichia coli (155 [47%]), Klebsiella pneumoniae (38 [11.6%]), and Pseudomonas aeruginosa (28 [8.5%]). The most common antimicrobial used was ertapenem. A second dose antimicrobial was given for 290 procedures due to a urinary catheter after a urological procedure. The mean hospitalization time was 3.97 ± 3.42 days. None of the patients developed infectious complications. Conclusions: This study has demonstrated that a single dose of parenteral antimicrobial drug administered 30-60 minutes before the urologic procedures and a second dose in the presence of a post-procedure catheter, was adequate to prevent post-procedure septicemia and urinary tract infection.

Neurotoxicity is an unusual side effect of carbapenems, and it has been reported most commonly presenting as seizures, encephalopathy and hallucinations. Ertapenem neurotoxicity most classically presents as seizures in patients with end-stage renal disease (estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2). We present a patient with a baseline eGFR of 30–59 mL/min/1.73 m2 with acute kidney injury who developed non-seizure neurotoxicity after ertapenem exposure. This patient is a middle-aged Caucasian man who received intravenous ertapenem for treatment of empyema. Although the empyema improved, he developed delirium beginning on day 7 of ertapenem. The delirium progressed to constant agitation and visual hallucinations requiring transfer to the intensive care unit with eventual intubation for airway protection. No improvement in mental status was observed with cessation of other medications. Ertapenem was discontinued and within 24 hours, he was extubated, and his mental status returned to baseline. He was discharged from the hospital the following day. The timely resolution after ertapenem discontinuation makes ertapenem-induced encephalopathy the most likely explanation for this patient’s course.

Using first-principles density functional theory (DFT), this study examines the improved chemical catalytic performance and biochemical sensing capabilities of iron (Fe) and gold (Au) nanoclusters decorated flawless γ-graphyne (GPN) as nanocarriers for the Ertapenem (EPM) antibiotic drug, in contrast to pristine γ-graphyne. The evaluation of binding energy analysis, it has been noted that perfect GPN (-0.96 eV), Au-decorated GPN (-1.852 eV), as well as Fe-decorated GPN (-1.520 eV), can be suitable candidates for drug delivery, as the binding energy falls in the physisorption to chemisorption range. There is a red shift in the ultraviolet-visible (UV-Vis) spectrum when EPM is adsorbed on the Fe- and Au-decorated GPN surfaces in comparison to the pristine substrates. Based on thermodynamic parameters, the values of Gibbs free energy changes (ΔG) and enthalpy change (ΔH) illustrate a strong interaction between EPM and the Au-decorated GPN (F: -1.130 and − 2.288 eV) in contrast to EPM with the Fe-decorated GPN carrier (I: -1.190 and − 2.210 eV), indicating that the interaction is stable and spontaneous. The Fe-decorated GPN improves the adsorption of EPM with a small binding energy, facilitated by a greater charge transfer from the substrate as an electron donor to the drug. This phenomenon results in a significant rise in dipole moment and a change in the energy gap. The results indicate that Fe-decorated GPN surface can serve as carriers for delivering the EPM drug.

Laboratory grown biofilms are used to simulate bacterial growth in diverse environmental conditions and screen the effectiveness of anti-biofilm therapies. Recently, we developed a glass bead biofilm reactor that utilizes low broth volume to provide high-throughput biofilm growth for testing and translation across the research continuum (e.g., benchtop assays to preclinical models). Bioburden per mm 2 surface area of Staphylococcus aureus and Pseudomonas aeruginosa biofilms were comparable on beads and CDC Biofilm Reactor® coupons. In this study, we hypothesized that biofilms grown on beads would be more susceptible to ertapenem, moxifloxacin, and tobramycin than those grown on coupons. Results indicated a significant reduction in S. aureus bioburden on glass beads compared to glass coupons following treatment with ertapenem ( p = 0.005) and tobramycin ( p = 0.014). P. aeruginosa biofilms had smaller differences in antibiotic response between the two systems. There was a significantly greater reduction in bead P. aeruginosa biofilm than coupon when treated with tobramycin ( p = 0.035). This work offered insight into how the bead biofilm reactor could be used as a tool for antibiotic screening and translation across the continuum of in vitro to in vivo systems that support development of antimicrobial technology.