Intravenous Ertapenem Research Articles

Minimizing infectious complications following transrectal prostate biopsy: a proposal for a risk-adapted antibiotic treatment strategy with Ceftriaxone and Ertapenem as key components.

To investigate the effect of pre-biopsy rectal swab and urine screening combined with a risk-adapted antibiotic treatment strategy on reducing post-biopsy infections (PBIs) following multiparametric magnetic resonance imaging (mpMRI)/ transrectal ultrasound (TRUS) fusion-targeted transrectal prostate biopsy (TRPBx). 1119 Patients undergoing mpMRI-TRUS fusion TRPBx between June 2017 and February 2024 were included. Patients were screened for rectal extended-spectrum beta-lactamase (ESBL)/multi-resistant gram-negative (MRGN) and urinary pathogens. Standard-risk patients (rectal non-ESBL/MRGN-carriers) either received Cefuroxime (2017-2020) or Ceftriaxone (2020-2024) intravenously before biopsy. For high-risk patients (rectal ESBL/MRGN-carriers) intravenous Ertapenem was used. Patients with positive urine cultures received oral targeted prophylaxis. PBIs were the primary outcome of the study. We used uni- and multivariable logistic regression analysis (MLRA) to reveal predictors for the main outcome. Rectal ESBL/MRGN prevalence was 5.5%. For standard-risk patients, PBI-rates were 8.1% and 0.24% for Cefuroxime and Ceftriaxone (p < 0.0001), respectively. Only 1.7% of high-risk patients treated with Ertapenem developed PBI. On MLRA, Cefuroxime (OR 38.7, 95%-CI: 10.9-246), oral Ciprofloxacin (OR 103, 95%-CI: 10.8-994), other oral targeted antibiotics (OR 42.7, 95%-CI: 1.86-496) (reference Ceftriaxone, all p < 0.005) were significant predictors for PBI whereas Ertapenem (OR 7.30 95%-CI: 0.34-77.4, p = 0.11) was not. By integrating rectal swab ESBL/MRGN and urine screening, we developed a tailored antibiotic treatment strategy, resulting in low PBI-rates following TRPBx. Carbapenem-based treatment of high-risk patients is crucial. Ceftriaxone should be considered for routine use in standard-risk patients as it offers very low PBI-rates.

THE OUTCOME OF ANTIBIOTICS VS OPEN APPENDECTOMY FOR ACUTE NON-PERFORATED APPENDICITIS

Acute appendicitis is a common surgical emergency. While appendectomy has been the conventional treatment for this condition, recent advancements in antibiotic therapy have led to exploring the use of antibiotics as a non-surgical alternative for treating non-complicated acute appendicitis. Objective: The objective of the present study was to compare the outcomes of administering antibiotics and performing emergency appendicectomy in a cohort of individuals diagnosed with non-perforated acute appendicitis based on CT evaluation. Methods: After the ethical approval from the institutional review board, this randomised control trial was conducted at Combined Military Hospital Jhelum from July 2022 to December 2023. The patients were randomly assigned, using a closed envelope method, to either have open appendectomy (Group A, n=60) or receive antibiotic therapy (Group B, n=60) with intravenous ertapenem. Open appendectomy was conducted utilising the McBurney technique. The patient’s outcomes were assessed during their hospitalization period, specifically on days 0, 1, and 2, and by telephone interviews one week and two months following the intervention. Pain scores were collected at two specific time points, one week and two months after randomisation, utilising a visual analogue scale (VAS). Results: No significant differences were observed in the baseline characteristics in both groups. Mean± S.D of the pain experience of the study participants in both groups was 4.16±1.04 and 3.68±1.02 (days) (P value=0.008). Mean± S.D of the hospital stay of the study participants in both groups was 3.13±0.87 and 3.16±0.83 (days) (P value=0.843). A significant difference in the VAS score was observed (p &lt;0.0001) in the participants of both groups at discharge and after a one-week follow-up period. Conclusion: The findings of the study indicate that a significant proportion of individuals who received antibiotic therapy for non-perforated acute appendicitis did not necessitate the surgical procedure of appendectomy within the two-month post-treatment observation period.

Efficacy and Durability of Intravenous Ertapenem Therapy for Recalcitrant Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a debilitating follicular skin disorder in which bacterial colonization is typical. Oral antibiotic efficacy can be unreliable; however, selective intravenous antibiotics, specifically ertapenem, may provide favorable clinical outcomes. To explore optimal course duration, efficacy, and patient satisfaction associated with intravenous ertapenem for HS. This retrospective review of the medical records of 98 patients with HS between 2018 and 2022 measured and evaluated patient outcomes before and after treatment with intravenous ertapenem. Participants were followed up in a telephone survey assessing patient perspectives and satisfaction. All of those included in this study received medical care from the Albert Einstein College of Medicine's Montefiore HS Center. Patients were treated with 1 g of ertapenem that was self-administered at home through a peripheral intravenous central catheter using an elastomeric pump for 12 to 16 weeks. Antiandrogens and immunomodulatory biologic therapies initiated prior to ertapenem were maintained throughout the treatment course. The primary outcomes, encompassing clinical severity (evaluated through the HS Physician Global Assessment score [a 6-point scale ranging from clear to very severe] and a numerical rating scale for pain [an 11-point scale in which a score of 0 indicates no pain and a score of 10 indicates the worst possible pain]) and markers of inflammation (such as leukocytes, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6), were measured at baseline, the midcourse of intravenous ertapenem treatment, at the end of the course, and posttherapy. Bacterial abundance was also examined at these 4 points, and patient satisfaction was assessed during follow-up. A total of 98 patients (mean [SD] age, 35.8 [13.0] years; 61 [62.2%] female) with HS were treated with intravenous ertapenem. The self-reported racial distribution included 3 individuals identifying as Asian (3.1%), 59 as Black/African American (60.2%), 13 as White (13.3%), and 23 as either other or unknown (23.5%). Additionally, 24 participants (24.5%) reported Spanish/Hispanic/Latino ethnicity. The mean (SD) treatment duration spanned 13.1 (4.0) weeks, with posttherapy follow-up occurring after 7.8 (3.6) weeks. From baseline to posttherapy follow-up, significant reductions were found in the mean (SD) HS Physician Global Assessment scores (3.9 [1.0] vs 2.7 [1.2]; P < .001) and the numerical rating scale for pain (4.2 [3.3] vs 1.8 [2.7]; P < .001), C-reactive protein (5.4 [11.4] vs 2.4 [2.0] mg/dL; P < .001), interleukin-6 (25.2 [21.1] vs 13.7 [13.9]; P < .001), and leukocytes (11.34 [3.9] vs 10.0 [3.4]; P < .001). At follow-up, 76 patients (78.0%) participated in the telephone survey, where 63 (80.3%) reported medium to high satisfaction; further, 69 (90.8%) would recommend ertapenem to other patients. In this retrospective review of medical records and telephone survey, treating HS with intravenous ertapenem, administered for a mean of 13 weeks, was associated with improvement in clinical and inflammatory markers, as well as heightened patient satisfaction. Nonetheless, this approach should be monitored for the emergence of antimicrobial resistance given a longer than standard treatment course.

Impact of antibiotic pharmacokinetics in urine on recurrent bacteriuria following treatment of complicated urinary tract infections.

The clinical relevance of bacteriuria following antibiotic treatment of complicated urinary tract infections in clinical trials remains controversial. We evaluated the impact of urine pharmacokinetics on the timing of recurrent bacteriuria in a recently completed trial that compared oral tebipenem pivoxil hydrobromide to intravenous ertapenem. The urinary clearance and urine dwell time of ertapenem were prolonged relative to tebipenem and were associated with a temporal difference in the repopulation of bladder urine with bacteria following treatment, potentially confounding the assessment of efficacy.

Pivmecillinam with Amoxicillin/Clavulanic acid as step down oral therapy in febrile Urinary Tract Infections caused by ESBL-producing Enterobacterales (PACUTI)

BackgroundOral treatment alternatives for febrile urinary tract infections are limited in the era of increasing antimicrobial resistance. We aim to evaluate if the combination of pivmecillinam and amoxicillin/clavulanic acid is non-inferior to current alternatives for step-down therapy in adult patients with febrile urinary tract infection.MethodsWe plan to perform an investigator-initiated non-inferiority trial. Adult hospitalised patients treated with 1–5 days of intravenous antibiotics for acute febrile urinary tract infection caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales will be randomised 1:1 to either control (7–10 days of either oral ciprofloxacin 500 mg twice daily or oral trimethoprim–sulfamethoxazole 800 mg/160 mg twice daily or intravenous ertapenem 1 g once daily, depending on sex, drug allergy, glomerular filtration rate and susceptibility testing) or intervention (10 days of pivmecillinam 400 mg three times daily and amoxicillin/clavulanic acid 500/125 mg three times daily). The primary outcome will be clinical cure 10 days (+/− 2 days) after antibiotic treatment completion. Clinical cure is defined as being alive with absence of fever and return to non-infected baseline of urinary tract symptoms without additional antibiotic treatment or re-hospitalisation (for urinary tract infection) based on a centralised allocation-blinded structured telephone interview. We plan to recruit 330 patients to achieve 90% power based on a sample size simulation analysis using a two-group comparison, one-sided alpha of 2.5%, an absolute non-inferiority margin of 10% and expecting 93% clinical cure rate and 10% loss to follow-up. The primary endpoint will be analysed using generalised estimated equations and reported as risk difference for both intention-to-treat and per protocol populations. Patients are planned to be recruited from at least 10 centres in Sweden from 2023 to 2026.DiscussionIf the combination of pivmecillinam and amoxicillin/clavulanic acid is found to be non-inferior to the control drugs there are potential benefits in terms of tolerability, frequency of interactions, outpatient treatment, side effects, nosocomial infections and drive for further antimicrobial resistance compared to existing drugs.Trial registrationNCT05224401. Registered on February 4, 2022

First Report of Immunoglobulin G4-related Hepatic Inflammatory Pseudotumor in Transplanted Liver.

Immunoglobulin (Ig)G4–related hepatic inflammatory pseudotumor (IgG4-HIPT) is a rare subset of IgG4-related disease characterized by IgG4-positive plasma cell infiltration and fibrosis.1 Only 28 cases have been reported, all occurring in native livers.1-3 We report herein the first case of IgG4-HIPT developing in a transplanted liver. All ethical approval and consent procedures were approved by the Medical Ethical Committee of Icahn School of Medicine at Mount Sinai. According to the institutional guidelines, the patient’s signed privacy consent is not necessary for a single case report with deidentified patient-specific information. Our patient, who is a 62-y-old women who underwent liver transplantation for primary biliary cholangitis 14 y prior, presented with bacteremia. Laboratory tests showed normal white blood cell count, elevated gamma-glutamyl transferase 101 U/L (normal, 8–35), normal alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin. Blood culture was positive for methicillin-resistant Staphylococcus aureus and Klebsiella oxytoca. Serological tests for hepatitis A, B, C, and E; cytomegalovirus; and Epstein-Barr virus were negative. Serum total IgG 1654 mg/dL (normal, 586–1602) and IgG4 171 mg/dL (normal, 2–96) were elevated. Computed tomography (Figure 1A) and magnetic resonance imaging (Figure 1C–E) of the abdomen revealed a 6-cm infiltrative mass in segment 8 of the liver. A biopsy of the lesion demonstrated parenchymal collapse replaced with fibrosis and sheets of plasma cells (Figure 1F). Immunohistochemical stains showed up to 150 IgG4-positive plasma cells per high power field and an IgG4:IgG ratio of 60% (Figure 1G and H). There was no evidence of malignancy, recurrent primary biliary cholangitis, acute cellular rejection, or chronic rejection, and a diagnosis of IgG4-HIPT was rendered. Given the patient’s bacteremia, she was started on intravenous daptomycin and ertapenem. Prednisone was deferred because she was asymptomatic from the lesion. The patient was restarted on mycophenolate mofetil 1 mo postdischarge. Repeat computed tomography of the abdomen 7 mo later demonstrated the decreased size of the lesion to 2.3 cm (Figure 1B).FIGURE 1.: Radiology features (A–E). A, Contrast-enhanced computed tomography images demonstrate an infiltrative enhancing mass in segment 8 measuring 6 cm (arrow). B, Follow-up postcontrast computed tomography after 7 mo demonstrates the decreased conspicuity and size of the lesion (measuring 2.3 cm, arrow). Contrast-enhanced MRI obtained during the (C) arterial, (D) portal venous, and (E) delayed venous phases demonstrates an ill-defined lobulated infiltrative progressively enhancing mass (arrow). Microscopic and immunohistochemical features (F–H). F, The inflammatory cells consist predominantly of lymphocytes and plasma cells (arrow) (hematoxylin and eosin stain ×200). The inflammatory cells demonstrated diffuse reactivity for (G) cluster of differentiation 138 and (H) immunoglobulin G4. MRI, magnetic resonance imaging.IgG4-related disease is generally described as an autoimmune disease because the oligoclonal expansions of both activated B cells and cytotoxic CD4+ T cells were considered central to the process.4 In our case, the IgG4-HIPT developed in a liver allograft in a patient on immunosuppression (tacrolimus target trough level 2–6 ng/dL, mycophenolate mofetil 500 mg twice daily). It may seem counterintuitive that an autoimmune process may develop in such a setting. On the other hand, infections such as Escherichia coli and Klebsiella may also incite an IgG4-predominant inflammatory response.3 In our case, the patient developed bacteremia with methicillin-resistant Staphylococcus aureus and Klebsiella at the time the liver mass was noted. Bacterial translocation from the gut to the portal circulation may have provoked an intrahepatic inflammatory response. This theory was further supported by partial or complete treatment response observed in the current and prior reported cases2 upon administration of antibiotics. Diagnosing IgG4-HIPT is challenging because of its rarity and overlapping clinical and radiological features with malignancy. Because IgG4-HIPT is clinically benign, the recognition of this entity is important to avoid unnecessary treatment.

Evaluation of Oral Tebipenem as a Step-Down Therapy following Intravenous Ertapenem against Extended-Spectrum β-Lactamase-Producing Escherichia coli in a Hollow-Fiber In Vitro Infection Model.

Tebipenem is an orally bioavailable carbapenem in development for the treatment of patients with complicated urinary tract infections. Herein, we describe the results of studies designed to evaluate tebipenem's potential as an oral (p.o.) transition therapy from intravenous (i.v.) ertapenem therapy for the most common uropathogen, Escherichia coli. These studies utilized a 7-day hollow-fiber in vitro infection model and 5 extended-spectrum β-lactamase-producing E. coli challenge isolates. Human free-drug serum concentration-time profiles for tebipenem 600 mg p.o. every 8 h and ertapenem 1 g i.v. every 24 h were simulated in the hollow-fiber in vitro infection model. Samples were collected for bacterial density and drug concentration determination over the 7-day study period. Generally, ertapenem monotherapy resulted in a greater reduction in bacterial density than did tebipenem monotherapy. In the treatment arms in which ertapenem dosing was stopped following dosing for 1 or 3 days, immediate bacterial regrowth occurred and matched that of the growth control. Finally, in the treatment arms in which ertapenem dosing was stopped following dosing for 1 or 3 days and tebipenem dosing was initiated for the remainder of the 7-day study, the intravenous-to-oral transition regimen reduced bacterial burdens and prevented regrowth. Given that transition from intravenous to oral antibiotic therapy has been shown to reduce hospital length of stay, nosocomial infection risk, and cost, and improve patient satisfaction, these data demonstrate tebipenem's potential role as an oral transition agent from intravenous antibiotic regimens within the antibiotic stewardship paradigm.

2236. Effectiveness of TBP-PI-HBr in Patients with Instrumentation, Anatomic or Functional Abnormalities: Secondary Analysis from ADAPT-PO

Abstract Background Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral carbapenem with activity against Enterobacterales uropathogens, including drug resistant strains. The ADAPT-PO trial demonstrated the non-inferiority of oral TBP-PI-HBr vs. intravenous (IV) ertapenem (ERT) in treating patients with cUTI and/or acute pyelonephritis (AP). Patients with certain anatomical disorders, functional (metabolic or neurological) disorders and/or urinary tract instrumentation (i.e., indwelling catheters) are at increased risk for poor outcomes and recurrent bacteriuria. This secondary analysis of ADAPT-PO evaluated outcomes in patients with various cUTI risk factors. Methods ADAPT-PO was a Phase 3 multinational, double-blind, double-dummy trial evaluating oral TBP-PI-HBr vs. IV ERT in 1372 hospitalized adult patients with cUTI/AP. Patients were randomized 1:1 to oral TBP-PI-HBr or IV ERT for 7-10 days. The primary efficacy endpoint was overall response (composite favorable clinical and microbiologic response) in the microbiological intent-to-treat (micro-ITT) population. Overall outcomes were assessed among patients with identified with at least one cUTI risk factor at baseline. Results At baseline, 382/449 (85.1%) and 361/449(86.2%) of patients in the TBP-PI-HBr and ERT arms, respectively had ≥1 risk factor and 289 (64.4%) and 268 (64.2%) had ≥2 risk factors. Anatomical abnormalities and/or urinary track instrumentation were present in 252 (56.1%) TBP-PI-HBr and 242 (57.8%) ERT patients; functional abnormalities were present in 90 (20.0%) and 85(20.3%) respectively). Among patients with ≥1 risk factor, overall response at TOC was 56.3% and 59.6% with TBP-PI-HBr and ERT, respectively, vs. 73.1% and 74.1% among those with no risk factors. Clinical response rates at TOC were high and similar in both arms in patients with (≥92.9%) and without (≥91.4%) risk factors whereas microbiologic responses were more variable between the 2 subsets. Conclusion In cUTI patients with ≥1 risk factor for complicated disease at baseline, outcomes were comparable between oral TBP-PI-HBr and IV ERT. As expected, these patients were at higher risk for recurrent bacteriuria. Overall responses in both groups were higher among patients without these risk factors. Disclosures Angela K. Talley, MD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Paul B. Eckburg, MD, AN2 Therapeutics: Stocks/Bonds|Spero Therapeutics: Advisor/Consultant Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Gary E. Moore, PhD, Spero Therapeutics: Advisor/Consultant Nivedita Bhatt, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Lori A. Muir, B.Sc., Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Lori A. Muir, B.Sc., Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds David Melnick, MD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds.

1839. Impact of Hypoalbuminemia on Ceftriaxone Treatment Failure in Patients With Enterobacterales Bacteremia

Abstract Background Ceftriaxone (CRO) is a third-generation cephalosporin that is commonly prescribed due to its robust Gram-negative activity and lack of renal dose adjustments. It is also highly protein bound allowing for once daily dosing. In patients with hypoalbuminemia, however, the proportion of free drug is increased thus increasing the rate at which CRO is renally eliminated. This increased clearance could lead to lower serum concentrations and increased risk of treatment failure. Methods We performed a retrospective, cohort study to assess the impact of hypoalbuminemia (serum albumin ≤ 2.5 g/dL) on treatment failure among patients with monomicrobial Enterobacterales bacteremia. Adult patients who received &amp;gt; 72 hours of CRO therapy for susceptible Enterobacterales bacteremia between May 1, 2016 and April 30, 2021 were eligible for inclusion. The primary outcome of treatment failure was a composite of inpatient mortality or escalation to an intravenous anti-pseudomonal antibiotic or ertapenem. Secondary outcomes included hospital length of stay, total duration of antibiotic therapy, and time to infection resolution. Baseline characteristics and outcomes were compared using R Studio (Version 4.1.0) in a 1:1 propensity-matched cohort. Results After propensity score matching, 142 patients were included in each study group. The most common organisms in our cohort were Escherichia coli (71.5%), Klebsiella pneumoniae (14.1%), and Proteus mirabilis (5.3%). The most frequently implicated source of infection was the urinary tract (71.5%). Interestingly, treatment failure was numerically higher in the hypoalbuminemia group but was not statistically significant (12.0% vs. 7.7%, p = 0.23). All secondary outcomes were similar between groups. Among the subgroup of patients admitted to the ICU at baseline, the difference in treatment failure was even greater between patients with hypoalbuminemia and those without (23.3% vs. 7.5%, P = 0.07). Conclusion Hypoalbuminemia did not appear to have a significant impact on clinical outcomes among patients with Enterobacterales bacteremia treated with CRO. However, critically ill patients may be subject to higher incidence of treatment failure in the presence of hypoalbuminemia. Disclosures All Authors: No reported disclosures.

A Systematic Review and Meta-analysis of Efficacy of Carbapenems versus Other Best Available Antibiotics in the Management of Patients with Urinary Tract Infections

Introduction: Carbapenems are found in high concentrations in urine and are mainly eliminated by the kidney. Hence, they are the preferred treatment for pyelonephritis and complicated urinary tract infections (cUTIs) caused by extended-spectrum β-lactamase (ESBL) producing bacteria. The recent emergence of bacterial resistance to carbapenems has resulted in the need to search for alternative treatments for complicated UTIs. This review aims to evaluate the efficacy of Carbapenems versus Piperacillin/tacobactam (or the best available antibiotic therapy) in the management of pyelonephritis in patients with upper UTIs.&#x0D; Methods: A systematic review was carried out to compile all relevant studies on the use of Carbapenems versus Piperacillin/tacobactam in the treatment of upper urinary tract infections, namely pyelonephritis. A meta-analysis was carried out of the selected studies, including clinical trials composed of adult patients aged between 18 and 80 years old diagnosed with pyelonephritis. Primary screening of eligible studies was followed by the removal of duplicates and exclusion of non-eligible and unavailable full-text trials.&#x0D; Results: This review included four studies on the treatment of complicated pyelonephritis. The number of patients included per study varied and ranged from 62 to 421 cases. Different types and regimes of carbapenems were used, including intravenous Meropenem-Vaborbactam, Meropenem, Biapenem, Doripenem, or Ertapenem. The included studies compared carbapenems to Piperacillin/tazobactam or other best available therapies, such as third-generation cephalosporin. For microbial failure, the overall risk ratio was 0.95 with a confidence interval range between 0.62 and 1.45, and for clinical failure, the overall risk ratio was 0.86 with a confidence interval range between 0.51 and 1.45.&#x0D; Conclusions: According to the meta-analysis, the included studies showed that Carbapenems are not inferior to the comparators for the management of complicated urinary tract infections.

Nocardia farcinica pituitary abscess in an immunocompetent patient: illustrative case.

Pituitary abscess is a rare clinical entity, typically precipitated by Staphylococcus, Pseudomonas, or Aspergillus infection. Although Nocardia species-associated central nervous system abscesses have been documented in immunocompromised patients, no case of Nocardia pituitary abscesses has been previously reported. A 44-year-old man presented with hemoptysis and was found to have a cavitary right lung nodule, which was presumed histoplasmosis, prompting antifungal treatment. Several months later, he developed panhypopituitarism. Magnetic resonance imaging identified a pituitary mass, which subsequently underwent transsphenoidal endoscopic biopsy. Infectious workup was negative, and the patient was discharged on intravenous ertapenem therapy. Over several months, he developed progressive headaches, and updated imaging confirmed interval enlargement of the mass with new cavernous sinus invasion. He underwent repeat endoscopic biopsy, which yielded positive cultures for Nocardia farcinica and prompted successful treatment with trimethoprim-sulfamethoxazole and linezolid. The current study highlights a previously unreported clinical entity, the first pituitary abscess attributable to Nocardia sp. or N. farcinica, which arose in a young, immunocompetent individual. Although rare, atypical infections represent an important component in the differential diagnosis for sellar mass lesions.

ACQUIRED BRONCHOBILIARY FISTULA PRESENTING AS COUGH

ACQUIRED BRONCHOBILIARY FISTULA PRESENTING AS COUGH

S2500 Gastrosplenic Fistula - An Open and Closed Case

Introduction: In this case, we will discuss endoscopic treatment for immunocompromised patients with gastrosplenic fistulas. Case Description/Methods: A 36-year-old White female with history of diffuse large B cell lymphoma (DLBCL) on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy presented with neutropenic fever, persistent cough with deep inspiration, and burning pain in her left shoulder that had worsened since chemotherapy 2 weeks prior. On admission, she was tachycardic and afebrile. White blood cell count was 1,200/mm3, absolute neutrophil count 120/mm3, and blood cultures were negative. CT demonstrated improved splenomegaly measuring 6.9 x 7.0 cm (previously 13 x 11 cm) and moderate gas and fluid within the spleen with suspected fistulous communication to the adjacent greater curvature of the stomach. An upper GI series confirmed gastrosplenic fistula (GSF) and fluid collection in the spleen. Gastroenterology and interventional radiology (IR) were consulted. Endoscopy revealed diffuse, severely congested mucosa in the gastric fundus and body, causing difficulty visualizing the fistula. An endocap was attached to the endoscope to assist with visualization. A 5 mm fistula with ulceration was found on the greater curvature of the gastric body. Argon plasma coagulation was performed for tissue devitalization in and around the fistula. The scope was then outfitted with an over-the-scope clip, which successfully closed the fistula (Figure). IR then placed an abdominal drain, and fluid cultures grew Streptococcus constellatus, Streptococcus anginosus, Lactobacillus rhamnosus, and Parvimonas micra. Empiric antibiotics were changed to intravenous ertapenem. The patient was able to tolerate a regular diet. Three weeks later, CT abdomen revealed significant decrease in size of splenic gas and fluid collections. Discussion: GSFs are a rare complication in patients with lymphoma and occur almost exclusively in patients with DLBCL. This patient did not present with typical features such as melena, hematochezia, severe sepsis, severe abdominal pain, nausea, vomiting, or hematemesis. It is important to consider GSF in patients with DLBCL presenting with GI issues. The overwhelming majority of GSF cases are surgical emergencies, but not every case will require surgical intervention. This can be important in patients at increased risk of surgical morbidity and mortality. A GI consult could save patients from unnecessary risk and financial burden.Figure 1.: A. Gastrosplenic fistula (gastric body) B. After APC C. After Clip Deployment.

Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection

BackgroundThere is a need for oral antibiotic agents that are effective against multidrug-resistant gram-negative uropathogens. Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem with activity against uropathogenic Enterobacterales, including extended-spectrum beta-lactamase–producing and fluoroquinolone-resistant strains.MethodsIn this phase 3, international, double-blind, double-dummy trial, we evaluated the efficacy and safety of orally administered tebipenem pivoxil hydrobromide as compared with intravenous ertapenem in patients with complicated urinary tract infection or acute pyelonephritis. Patients were randomly assigned, in a 1:1 ratio, to receive oral tebipenem pivoxil hydrobromide (at a dose of 600 mg every 8 hours) or intravenous ertapenem (at a dose of 1 g every 24 hours) for 7 to 10 days (or up to 14 days in patients with bacteremia). The primary efficacy end point was overall response (a composite of clinical cure and favorable microbiologic response) at a test-of-cure visit (on day 19, within a ±2-day window) in the microbiologic intention-to-treat population. The noninferiority margin was 12.5%.ResultsA total of 1372 hospitalized adult patients were enrolled; 868 patients (63.3%) were included in the microbiologic intention-to-treat population (50.8% of whom had complicated urinary tract infections and 49.2% of whom had pyelonephritis). An overall response was seen in 264 of 449 patients (58.8%) who received tebipenem pivoxil hydrobromide, as compared with 258 of 419 patients (61.6%) who received ertapenem (weighted difference, −3.3 percentage points; 95% confidence interval [CI], −9.7 to 3.2). Clinical cure at the test-of-cure visit was observed in 93.1% of the patients in the microbiologic intention-to-treat population who received tebipenem pivoxil hydrobromide and 93.6% of patients who received ertapenem (weighted difference, −0.6 percentage point; 95% CI, −4.0 to 2.8); the majority of patients with microbiologic response failures at the test-of-cure visit were asymptomatic patients with recurrent bacteriuria. Secondary and subgroup analyses were supportive of the primary analysis. Adverse events were observed in 25.7% of patients who received tebipenem pivoxil hydrobromide and in 25.6% of patients who received ertapenem; the most common adverse events were mild diarrhea and headache.ConclusionsOral tebipenem pivoxil hydrobromide was noninferior to intravenous ertapenem in the treatment of complicated urinary tract infection and acute pyelonephritis and had a similar safety profile. (Funded by Spero Therapeutics and the Department of Health and Human Services; ADAPT-PO ClinicalTrials.gov number, NCT03788967.)

Antibiotics versus placebo in adults with CT-confirmed uncomplicated acute appendicitis (APPAC III): randomized double-blind superiority trial.

Non-operative management of uncomplicated acute appendicitis is an option, but omission of antibiotics from the regimen has not been tested. A double-blind, placebo-controlled, superiority RCT in adults with CT-confirmed uncomplicated acute appendicitis was designed to compare placebo with antibiotics (intravenous ertapenem followed by oral levofloxacin and metronidazole). The primary endpoint was treatment success (resolution resulting in discharge without appendicectomy within 10 days); secondary outcomes included pain scores, complications, hospital stay, and return to work. From May 2017 to September 2020, 72 patients with a mean(s.d.) age of 37.5 (11.1) years were recruited at five hospitals. Six were excluded after randomization (5 early consent withdrawals, 1 randomization protocol violation), 35 were assigned to receive antibiotics, and 31 to receive placebo. Enrolment challenges (including hospital pharmacy resources in an acute-care surgery setting) meant that only the lowest sample size of three predefined scenarios was achieved. The 10-day treatment success rate was 87 (95 per cent c.i. 75 to 99) per cent for placebo and 97 (92 to 100) per cent for antibiotics. This clinical difference of 10 (90 per cent c.i. -0.9 to 21) per cent was not statistically different for the primary outcome (1-sided P = 0.142), and secondary outcomes were similar. The lack of antibiotic superiority statistically suggests that a non-inferiority trial against placebo is warranted in adults with CT-confirmed mild appendicitis. Registration number: EudraCT 2015-003634-26 (https://eudract.ema.europa.eu/eudract-web/index.faces), NCT03234296 (http://www.clinicaltrials.gov).

Ertapenem-Induced Delirium

Neurotoxicity is an unusual iatrogenic effect associated with carbapenems, typically manifested as seizures or hyperactive delirium. We present an 89-year-old female patient with a medical history of hypertension and chronic kidney disease who was admitted for acute tracheobronchitis and anemia related to diverticular disease. As a complication, she developed acute cystitis caused by extended spectrum ß-lactamases producing Klebsiella pneumoniae, so intravenous ertapenem was started. On the second day of antibiotic therapy, the patient manifested visual hallucinations followed by an inattentive and lethargic state suggestive of a hypoactive delirium. An ertapenem-induced neurotoxicity was suspected. Upon substitution by meropenem, the patient improved, and symptom reversal occurred after 72 hours. We present a review of ertapenem-induced hallucinations and address pharmacokinetics aspects namely renal dysfunction and hypoalbuminemia that could potentiate encephalopathy. Although rare, clinicians should be aware of non-seizure ertapenem related neurotoxicity. Ready recognition can lead to rapid improvement and prevent dire outcomes.

Fosfomycin vs Ertapenem for Outpatient Treatment of Complicated Urinary Tract Infections: A Multicenter, Retrospective Cohort Study.

BackgroundWe sought to determine the comparative efficacy of fosfomycin vs ertapenem for outpatient treatment of complicated urinary tract infections (cUTIs).MethodsWe conducted a multicenter, retrospective cohort study involving patients with cUTI treated with outpatient oral fosfomycin vs intravenous ertapenem at 3 public hospitals in Los Angeles County between January 2018 and September 2020. The primary outcome was resolution of clinical symptoms 30 days after diagnosis.ResultsWe identified 322 patients with cUTI treated with fosfomycin (n = 110) or ertapenem (n = 212) meeting study criteria. The study arms had similar demographics, although patients treated with ertapenem more frequently had pyelonephritis or bacteremia while fosfomycin-treated patients had more retained catheters, nephrolithiasis, or urinary obstruction. Most infections were due to extended-spectrum β-lactamase–producing E. coli and Klebsiella pneumoniae, 80%–90% of which were resistant to other oral options. Adjusted odds ratios for clinical success at 30 days, clinical success at last follow-up, and relapse were 1.21 (95% CI, 0.68–2.16), 0.84 (95% CI, 0.46–1.52), and 0.94 (95% CI, 0.52–1.70) for fosfomycin vs ertapenem, respectively. Patients treated with fosfomycin had significant reductions in length of hospital stay and length of antimicrobial therapy and fewer adverse events (1 vs 10). Fosfomycin outcomes were similar irrespective of duration of lead-in intravenous (IV) therapy or fosfomycin dosing interval (daily, every other day, every third day).ConclusionsThese results would support the conduct of a randomized controlled trial to verify efficacy. In the meantime, they suggest that fosfomycin may be a reasonable stepdown from IV antibiotics for cUTI.

Leukemoid Reaction in a Case of Chronic Cholecystitis With Focal Mild Acute Inflammation

Leukemoid reaction is a rare condition of marked increase of the white blood cells (WBC) in the peripheral blood, mostly more than 50 × 109/L. Although its most common cause is infection, acute or chronic cholecystitis has been hardly mentioned. This report aimed to present the leukemoid reaction found in a Thai who had chronic cholecystitis with focal acute inflammation. A 74-year-old woman had low-graded fever and generalized vague abdominal discomfort for 2 days. The physical examination showed the body temperature 37.7 °C and unremarkable abdominal signs. Her blood tests showed: hemoglobin 9.0 g/L, WBC 52.48 × 109/L, neutrophil 91%, band form 1%, platelet 434 × 109/L, and alkaline phosphatase (ALP) 290 U/L. The blood cultures yielded no growth. The computed tomography of the abdomen revealed 2 stones in the common bile duct (CBD) causing obstruction; the gall bladder (GB) showed mild dilatation with thin wall containing multiple small gall stones; no pericholecystic fluid and normal size of spleen. She promptly underwent operative cholecystectomy, CBD choledochoscopy, stones removal and T-tube choledochostomy. Along with the surgery, intravenous ertapenem was also administered. The pathology of the gall bladder was chronic cholecystitis with focal mild acute inflammation. With these therapies, fever daily decreased and finally disappeared within 5 days meanwhile the WBC count also gradually diminished every day till 8.04 × 109/L within 7 days. The WBC count was still normal one month later. The diagnosis of leukemoid reaction was concluded and it was presumably be associated with chronic calculous cholecystitis with focal acute inflammation although the BCR-ABL translocation had never been explored.&#x0D;

Tebipenem pivoxil hydrobromide-No PICC, no problem!

Tebipenem pivoxil hydrobromide is a novel orally bioavailable prodrug of tebipenem, a carbapenem antimicrobial, that binds to penicillin-binding proteins, inhibiting the synthesis of the bacterial cell wall. This results in weakening of peptidoglycan, leading to lysis of bacterial cells. Tebipenem displays a broad spectrum of activity against anaerobic, gram-positive, and gram-negative pathogens, including extended-spectrum β-lactamase producing Enterobacterales. In a large phase 3clinical trial (ADAPT-PO), oral tebipenem pivoxil hydrobromide 600mg every 8h was shown to be non-inferior to intravenous ertapenem 1g every 24h. Overall response at test of cure was 58.8% [264/449] in the tebipenem pivoxil hydrobromide group compared to 61.6% [258/419] in the ertapenem group for the treatment of complicated urinary tract infections, including acute pyelonephritis. At the test of cure, clinical cure rates were 93.1% and 93.6% and microbiological eradication was 59.5% and 63.5% with tebipenem pivoxil hydrobromide and ertapenem, respectively. The most common adverse reactions associated with tebipenem pivoxil hydrobromide are diarrhea, headache, and nausea. As with other carbapenems, tebipenem pivoxil hydrobromide is expected to have the potential to decrease the seizure threshold and will likely require renal dosage adjustment for patients with altered renal function due to high renal clearance. If approved in the United States, tebipenem pivoxil hydrobromide can serve as a potential oral antimicrobial option to decrease hospital length of stay and prevent hospital admissions due to resistant pathogens.

Safety of Intravenous Push Ertapenem Compared to Intravenous Piggyback at a Tertiary Academic Medical Center

Background: Recent shortages of intravenous (IV) fluids have resulted in healthcare systems converting administration of many medications from IV piggyback (IVPB) to IV push (IVP). Administering medications via IVP presents numerous advantages; however, IV site reactions such as phlebitis and infiltration may occur. Objective: The objective of this analysis is to evaluate the infusion site safety of ertapenem given as peripheral IVP compared to IVPB in adult patients. Methods: This was an institutional review board–approved, single-center, retrospective study. Patients, ages 18 or older, receiving IV ertapenem were identified. The major endpoints analyzed were IV site reactions including phlebitis and infiltration. The Naranjo Nomogram was utilized to assess the causality of the reactions to determine the likelihood of whether the event was caused by the medication itself or other factors. Results: To date, 283 administrations (92 patients) in the IVP group and 319 administrations (82 patients) in the IVPB group were analyzed. There were 13 IV site reactions compared to 8 in the IVP vs IVPB group, respectively (P-value = 0.16). Ten of the events in the IVP group were deemed “possible” and 2 deemed “doubtful,” while the remaining event was considered “probable” per the Naranjo Nomogram. Of the events in the IVPB group, all 8 were found to be “possible.” Conclusion: The administration of IVP ertapenem showed comparable rates of infusion site reactions compared to IVPB. Implementation of IVP ertapenem appears to be associated with infusion site safety similar to IVPB and should be considered safe to administer.