Search Results (55)

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies. Cefmetazole (CMZ) and flomoxef (FMOX) are parenteral antibiotics that are widely used in Japan and have emerged as potential carbapenem alternatives. Repositioning these agents effectively addresses the clinical need for carbapenem-sparing strategies and outpatient ESBL-E management. This review aims to reposition CMZ and FMOX for real-world clinical practice by synthesizing basic research, clinical studies, and pharmacokinetics/pharmacodynamics (PKs/PDs) analyses, which suggest that these agents may be effective in treating ESBL-E infections—particularly urinary tract infections, as evidenced by their minimum inhibitory concentration (MIC) values. The clinical outcomes of these interventions have been comparable to those of carbapenems, which support their role in antimicrobial stewardship. Their PK/PD characteristics emphasize the importance of dose optimization to ensure therapeutic efficacy, whereas recent insights into resistance mechanisms provide a foundation for appropriate use. As novel antibiotic development takes substantial time, revisiting existing options is increasingly important. Notably, the Infectious Diseases Society of America’s 2024 guidance on antimicrobial resistance has omitted CMZ and FMOX, owing to which clinicians have limited guidance on their use, particularly in regions like Japan where these antibiotics are widely employed. By addressing this knowledge gap, the present review offers a comprehensive evaluation of these drugs and highlights their potential as intravenous agents in ESBL-E management. Furthermore, it highlights the ongoing challenge of ensuring effective oral step-down therapy in an outpatient setting to reinforce the global relevance of CMZ and FMOX in a broader treatment framework, underscoring their potential for outpatient administration where clinically appropriate. Full article

Background/Objectives: The increasing prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing organisms poses a significant clinical challenge worldwide due to limited oral treatment options. Tebipenem (TBPM), an oral carbapenem antibiotic, is currently approved only for pediatric use in Japan, with no adult indication established. International studies have shown promising results for ESBL-producing infections, but optimal dosing regimens for Japanese adults with varying renal function have not been established. This study aimed to determine the optimal TBPM dosing regimens for ESBL-producing Enterobacterales UTIs in Japanese patients stratified by renal function, providing evidence for potential adult approval applications in Japan. Methods: Monte Carlo simulations (MCSs) were performed using pharmacokinetic parameters derived from clinical trials in Japanese subjects. Various dosing regimens were evaluated across different creatinine clearance (CCR) ranges and minimum inhibitory concentrations (MICs). The pharmacokinetic/pharmacodynamic target was set at fAUC_0–24/MIC·1/tau ≥ 34.58, with a ≥90% probability of target attainment (PTA) considered optimal. Results: For patients with severe renal impairment (CCR < 30 mL/min), 150 mg q12 h achieved a >90% PTA against ESBL-producing organisms with an MIC of 0.03 mg/L. For moderate-to-severe renal impairment (30 ≤ CCR < 50 mL/min) and moderate renal impairment (50 ≤ CCR < 80 mL/min), 300 mg q8 h maintained a >90% PTA. For normal renal function (CCR ≥ 80 mL/min), 600 mg q8 h was required to achieve the target PTA. Conclusions: This first Japanese PK/PD analysis of TBPM in ESBL-producing UTIs provides evidence-based dosing recommendations across various renal function levels. TBPM, with appropriate renal-adjusted dosing, may offer an effective oral treatment option for patients who have traditionally required hospitalization for parenteral therapy. Full article

Background: The use of an elastomeric diffuser is favored to administer outpatient antibiotic therapy. A study published in 2022 highlighted the instability of several antibiotics in elastomeric devices at 37 °C. The objective was to evaluate the stability of nine time-dependent antibiotics that are unstable at 37 °C at lower concentrations and a reduced storage temperature of 32 °C. Methods: Chemical stability was assessed by pH measurement and high-performance liquid chromatography. Physical stability was evaluated by visual and subvisual inspection. The solutions were considered stable if the remaining drug percentage was ≥90%, the maximum variation in pH was less than 1, the particle count was within acceptable limits and the visual aspect remained unchanged after storage. Results: Solutions showing stability for 24 h are composed of 12.5 mg/mL cefiderocol in NS (normal saline) and 50–133 mg/mL piperacillin in NS-D5W (5% dextrose). Additionally, 12.5 mg/mL amoxicillin in NS; 12.5 mg/mL cefepime in NS-D5W; 12.5 mg/mL cefiderocol in D5W; 25 mg/mL cefiderocol in NS-D5W; 12.5 mg/mL cefotaxime in NS-D5W; 12.5 mg/mL cefoxitin in NS-D5W; 12.5 mg/mL ceftazidime in NS-D5W; 25 mg/mL ceftazidime in NS; 25 mg/mL cloxacillin in NS-D5W; and 25–50 mg/mL oxacillin in NS were shown to be stable for 12 h. Notably, 25 mg/mL amoxicillin in NS, 50 mg/mL cloxacillin in NS and 25 mg/mL oxacillin in D5W were shown to be stable for 8 h. Conclusions: These 12–24 h stability data indicate that these antibiotics can be administered by continuous infusion using only one–two elastomeric devices per day, facilitating outpatient parenteral antimicrobial therapy (OPAT). Full article

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to manage a broad range of infections, enabling patients to receive intravenous antibiotics safely outside inpatient settings. In this review, we examine the current landscape of OPAT practice across the United Kingdom (UK), assessing its clinical, economic, and operational impact. The benefits of OPAT for patients and the National Health Service (NHS), as well as its associated risks, are discussed. Additionally, we explore the challenges hindering its broader implementation within the UK. Finally, we highlight recent innovations and emerging applications of OPAT relevant to the NHS, underscoring key considerations for its future expansion and emphasising the need for a nationally coordinated strategy to realise its full potential. Full article

Background/Objectives: Elastomeric infusion pumps have emerged as a transformative tool in outpatient parenteral antimicrobial therapy (OPAT), enabling continuous intravenous administration outside hospital settings, enhancing patient autonomy, reducing healthcare costs, and playing a role in antimicrobial stewardship. This aim of this review is to update current evidence on antibiotic stability in elastomeric infusion pumps, analyzing environmental factors, clinical efficacy, and practical challenges associated with OPAT implementation. Methods: A narrative review was conducted using PubMed and the Cochrane Library, focusing on studies published between 2022 and 2025. Included studies assessed antibiotic stability in elastomeric pumps under real-world and laboratory conditions, examining factors such as temperature sensitivity, light exposure, and material interactions. Results: Findings indicate considerable variability in antibiotic stability, with some agents maintaining prolonged efficacy while others degrade rapidly under certain conditions. Antibiotics with greater stability are better suited for OPAT, whereas those prone to degradation present challenges for continuous infusion. Clinical studies report favorable treatment outcomes, including high cure rates and manageable adverse event profiles. However, discrepancies between laboratory-controlled conditions and real-world settings highlight the necessity for more comprehensive stability evaluations to ensure optimal antibiotic selection and administration in OPAT programs. Conclusions: Optimizing antibiotic formulations, standardizing stability protocols, and advancing elastomeric pump technologies are essential for enhancing OPAT effectiveness. Future research should focus on real-world simulation studies and refining device materials to expand the range of stable antibiotics, ensuring safer and more efficient outpatient antimicrobial therapy. Full article

Background: Children with short bowel syndrome (SBS) have abnormal intestinal anatomy, secretion, or motility, which can lead to small intestinal bacterial overgrowth (SIBO). In this paper, we describe our experience with SIBO in children with SBS, focusing on potential risk factors, clinical presentation, and antibiotic treatment. Methods: A single-center retrospective descriptive cohort study of all episodes of clinically suspected SIBO in 16 children with SBS on home parenteral nutrition (HPN) between January 2018 and December 2022 was performed. Results: The mean small bowel remnant was 47 cm (SD = 31.5), with an absent ileocecal valve in 61.5% (8/13). Five children (31.2%) had at least 1 episode of clinically suspected SIBO, with a total of 25 episodes. The most common clinical presentation was diarrhea (76%), followed by meteorism (56%), loss of appetite (48%), flatulence (48%), weight loss (36%), abdominal pain (25%), and vomiting (12%). Fifty-six percent (16/25) of SIBO episodes were treated with one type of antibiotic, 36% (9/25) with two types, and 8% (2/25) with three types. Symptom resolution was achieved in 56% (14/25) of SIBO episodes after one course of antibiotic therapy. Two children (12.5%) had refractory and recurrent SIBO episodes treated with cyclic antibiotic regimens. Conclusions: SIBO can affect the ability of children with SBS to successfully wean off HPN. Diagnostic tests have innate challenges, and early clinical suspicion is paramount. Antibiotic therapy should be individualized considering the child’s age, gastrointestinal anatomy, and the risk of SIBO recurrence. Full article

Background: Cholelithiasis is a rare disease in infants, and there is limited data on its risk factors and management. Objectives: To evaluate the risk factors, management, and response to medical treatment of cholelithiasis in infants. Methods: Infants diagnosed with cholelithiasis by ultrasound between 2018 and 2023 were retrospectively analyzed. Details of patient history, imaging findings, current symptoms, and treatments were reviewed. Results: Over 5 years, 98 infants were diagnosed with cholelithiasis. Thirty-three (33.7%) were girls, and the most common risk factors were the use of cephalosporin antibiotic therapy in 46.9%, sepsis in 30.6%, total parenteral nutrition in 29.6%, prematurity in 27.6%, congenital heart disease in 18.4%, and genetic disease (Down syndrome diagnosis in seven patients) in 16.3%. Only fifteen patients (15.3%) were symptomatic. Ursodeoxycholic acid (UDCA) treatment was given to 90.8% of patients, but nine of them used it for a short period or irregularly, and regular users were 81.6%. Gallstones disappeared in 46 patients (46.9%), including 14 (30.4%) without using UDCA regularly. The response rate to UDCA treatment was lower in preterm infants (p = 0.004). Gallstone resolution was higher in the nonusers, 14/18 (77.8%) versus 32/79 (40.5%) (p = 0.03). Acute cholecystitis was observed in only four patients; no other complications were noted. No infant required surgical or endoscopic treatment. Conclusions: UDCA should not be used routinely in children, especially infants, except in symptomatic children with a contraindication to surgery or to reduce clinical symptoms. In the absence of symptoms, patients may be monitored clinically. Full article

Introduction: Patients receiving biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatological conditions are at an increased risk of serious, potentially life-threatening, infection. However, the incidence, aetiology, and clinical course of serious infection in patients receiving b/tsDMARDs in tropical settings are incompletely defined. Methods: We retrospectively reviewed all patients with rheumatoid arthritis receiving b/tsDMARDs between October 2012 and October 2021, at Cairns Hospital in tropical Australia. The incidence, aetiology, and clinical course of serious infections (those requiring admission to hospital or parenteral antibiotics) were determined. Results: 310 patients had 1468 patient years of b/tsDMARD therapy during the study period; 74/310 (24%) had 147 serious infections translating to an overall risk of 10.0 episodes of serious infection per 100 patient years. The respiratory tract (50/147, 34%) and skin (37/147, 25%) were the most frequently affected sites. A pathogen was identified in 59/147 (40%) episodes and was most commonly Staphylococcus aureus (24/147, 16%). Only 2/147 (1%) were confirmed “tropical infections”: 1 case of Burkholderia pseudomallei and 1 case of mixed B. pseudomallei and community-acquired Acinetobacter baumannii infection. Overall, 13/147 (9%) episodes of serious infection required Intensive Care Unit admission (0.9 per 100-patient years of b/tsDMARD therapy) and 4/147 (3%) died from their infection (0.3 per 100-patient years of b/tsDMARD therapy). The burden of comorbidity and co-administration of prednisone were the strongest predictors of death or a requirement for ICU admission. Conclusions: The risk of serious infection in patients taking b/tsDMARDs in tropical Australia is higher than in temperate settings, but this is not explained by an increased incidence of traditional tropical pathogens. Full article

Background/Objective: Narrow-spectrum beta-lactam antibiotics such as benzylpenicillin and flucloxacillin are increasingly used in outpatient parenteral antimicrobial therapy (OPAT) programs to mitigate the adverse effects associated with broad-spectrum antibiotics. These beta-lactams require continuous administration via portable infusion devices during OPAT. However, the use of benzylpenicillin in OPAT requires special consideration because of its limited stability at elevated temperatures. Methods: We tested the benzylpenicillin stability, pH, and degradation of products in elastomeric pumps at different concentrations in saline and in buffered solution containing sodium citrate during a prolonged storage and at high temperatures (seven days at 2–8 °C followed by 24 h at 37 °C). Additionally, drug concentrations during intermittent bolus infusion and during OPAT were determined in five patients. The concentrations and degradation products of benzylpenicillin were measured using liquid chromatography mass spectrometry (LC-MS/MS). Results: Unbuffered benzylpenicillin solutions that were already degraded during refrigerator storage and analyte concentration were not measurable after 8 days. The stability of the buffered solutions was acceptable at all three of the tested concentrations (97.6 ± 1.3%, 96.3 ± 0.8%, and 94.9 ± 1.1% for 10 Mio IU, 20 Mio IU, and 40 Mio IU of benzylpenicillin). The stability was influenced by benzylpenicillin concentration, and several breakdown products were identified. Benzylpenicillin concentrations were measured in five patients during OPAT and ranged from 7.2 to 60 mg/L. Conclusions: Benzylpenicillin buffered with sodium citrate is a safe and convenient option for use in continuous infusions during OPAT and should be favored over broad-spectrum antibiotics. Therapeutic drug monitoring data indicate sufficient to high plasma levels when patients received benzylpenicillin as continuous infusions. Full article

Bacteremia and endocarditis are two clinical syndromes that, for decades, were managed exclusively with parenteral antimicrobials, irrespective of a given patient’s clinical condition, causative pathogen, or its antibiotic susceptibility profile. This clinical approach, however, was based on low-quality data and outdated expert opinions. When a patient’s condition has improved, gastrointestinal absorption is not compromised, and an oral antibiotic regimen reaching adequate serum concentrations is available, a switch to oral antibacterials can be applied. Although available evidence has reduced the timing of the oral switch in bacteremia to three days/until clinical improvement, there are only scarce data regarding less than 10-day intravenous antibiotic therapy in endocarditis. Many standard or studied oral antimicrobial dosages are smaller than the approved doses for parenteral administration, which is a risk factor for treatment failure; in addition, the gastrointestinal barrier may affect drug bioavailability, especially when the causative pathogen has a minimum inhibitory concentration that is close to the susceptibility breakpoint. A considerable number of patients infected by such near-breakpoint strains may not be potential candidates for oral step-down therapy to non-highly bioavailable antibiotics like beta-lactams; different breakpoints should be determined for this setting. This review will focus on summarizing findings about pathogen-specific tailoring of oral step-down therapy for bacteremia and endocarditis, but will also present laboratory and clinical data about antibiotics such as beta-lactams, linezolid, and fosfomycin that should be studied more in order to elucidate their role and optimal dosage in this context. Full article

(1) Background: The widespread use of MALDI-TOF coupled to mass spectrometry has improved diagnostic accuracy by identifying uncommon bacteria. Among Enterobacterales, Pantoea species have been seen to be implicated in several human infections, but their clinical and microbiological framework is currently based on a few anecdotal reports. (2) Methods: We conducted this five-year (2018–2023) single-center study aimed at investigating the prevalence and clinical and microbiological findings of Pantoea species bloodstream infections. (3) Results: Among the 4996 bloodstream infection Gram-negative isolates collected during the study period, Pantoea species accounted for 0.4% (n = 19) of isolates from 19 different patients, 5 of them being pediatric cases. Among Pantoea species isolates, P. agglomerans was the most frequently detected (45%; n = 9) followed by P. eucrina (30%; n = 6) and P. septica (15%; n = 3). Malignancy (35.7%) in adults and malignancy (40%) and cerebrovascular disease following meconium aspiration (40%) in pediatric patients as comorbidities and shivering and/or fever following parenteral infusion (36.8%) as a symptom/sign of Pantoea species bloodstream infection onset were the most frequently observed clinical features. Among adults, primary bloodstream infection was the most frequent (50%), whereas among pediatric patients, the most commonly identified sources of infection were catheter-related (40%) and the respiratory tract (40%). Overall, Pantoea species bloodstream infection isolates displayed high susceptibility to all the antibiotics except for ampicillin (63.2%), fosfomycin (73.7%), and piperacillin/tazobactam (84.2%). Targeted antibiotic treatment was prescribed as monotherapy for adults (71.4%) and combination therapy for pediatric patients (60%). The most prescribed antibiotic regimens were piperacillin/tazobactam (21.4%) in adults and meropenem- (40%) and aminoglycoside-containing (40%) antibiotics in pediatric patients. The overall 28-day all-cause mortality rate was 5.3% (n = 1). (4) Conclusions: The prevalence and 28-day mortality rate of Pantoea species bloodstream infections were low. The prescription of targeted therapy including broad-spectrum antibiotics could indicate an underestimation of the specific involvement of the Pantoea species in the onset of the disease, warranting further studies defining their pathogenic potential. Full article

Outpatient parenteral antimicrobial therapy (OPAT) is a useful treatment strategy against Pseudomonas aeruginosa and other multidrug-resistant bacteria. However, it is hindered by the lack of stability data for the administration of antibiotics under OPAT conditions. Our objective was to investigate the stability of nine antipseudomonal and broad-spectrum beta lactam antibiotics (aztreonam, cefepime, cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, meropenem/vaborbactam, and piperacillin/tazobactam) to allow the spread of OPAT programs. All the antibiotics were diluted in 500 mL 0.9% sodium chloride and stored at 4, 25, 32, and 37 °C for 72 h in two different devices (infusion bags and elastomeric pumps). The solutions were considered stable if the color, clearness, and pH remained unchanged and if the percentage of intact drug was ≥90%. All the antimicrobials remained stable 72 h under refrigerated conditions and at least 30 h at 25 °C. At 32 °C, all the antibiotics except for meropenem and meropenem/vaborbactam remained stable for 24 h or more. At 37 °C, only aztreonam, piperacillin/tazobactam, cefepime, cefiderocol, and ceftolozane/tazobactam were stable for at least 24 h. The stability results were the same in the two devices tested. All the antibiotics studied are actual alternatives for the treatment of antipseudomonal or multidrug-resistant infections in OPAT programs, although the temperature of the devices is crucial to ensure antibiotic stability. Full article

Hyperammonemia syndrome is a complication that has been reported to occur in 1–4% of lung transplant patients with mortality rates as high as 60–80%, making detection and management crucial components of post-transplant care. Patients are treated with a multimodal strategy that may include renal replacement therapy, bowel decontamination, supplementation of urea cycle intermediates, nitrogen scavengers, antibiotics against Mollicutes, protein restriction, and restriction of parenteral nutrition. In this review we provide a framework of pharmacologic mechanisms, medication doses, adverse effects, and available evidence for commonly used treatments to consider when initiating therapy. In the absence of evidence for individual strategies and conclusive knowledge of the causes of hyperammonemia syndrome, clinicians should continue to design multimodal regimens based on suspected etiologies, institutional drug availability, patient ability to tolerate enteral medications and nutrition, and availability of intravenous access. Full article

Chronic rhinosinusitis (CRS) is an important ENT pathology which affects about 5–12% of the general population. The treatment of CRS can be pharmacological (nasal sprays, douches, systemic antibiotics and steroids), surgical (endoscopic sinus surgery) or immunological according to established algorithms. CRS was divided for many years into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). New ways of classifying CRS by endotypes (presence of neutrophilia, eosinophilia, fibrosis, glandular hypertrophy and epithelial dysmorphisms) appeared after the most recent understandings of the pathophysiology of the disease. Other classifications divide CRS into primary and secondary forms, localized/diffuse types and anatomical presentation. A new type of treatment has been administered in the last years, biologics. For the moment, biologics are indicated just in the cases of the patients who have undergone ESS or have contraindications for surgery and have bilateral polyps and meet a minimum of three of the following criteria: the necessity for systemic therapies with oral or parenteral corticosteroids or contraindications to systemic steroids, significant loss of smell or impaired QoL score, comorbid asthma and type 2 inflammation. This article aims to present the most relevant studies which used the three types of biologics (anti-IgE, anti-IL5 and anti-IL4/IL3) and wishes to increase the awareness of this new type of treatment that can be used in some CRS cases. Full article

This retrospective study aimed to investigate the impact of microorganisms identified in the reproductive tract on disorders during the early adaptation period in newborns. A cohort of 823 patients and cervical canal cultures were analyzed to identify the presence of microorganisms. Newborns included in the study were divided into two groups due to the number of pathogens identified in the swab from the cervical canal of the mother. The first group consisted of newborns whose mothers had one pathogen identified (N = 637), while the second group consisted of newborns whose mothers had two or more pathogens identified (N = 186). The analysis of disorders of the early adaptation period included the incidence of respiratory distress syndrome, the number of procedures performed with the use of CPAP, oxygen therapy, antibiotic therapy and parenteral nutrition. Respiratory distress syndrome was more common in group II than in group I (85 vs. 31, p = 0.001). In group II, CPAP (63 vs. 21, p = 0.001), oxygen therapy (15 vs. 8, p = 0.02) and antibiotics were used more frequently (13 vs. 8, p = 0.01). The findings of this study revealed that the number of pathogens colonizing the reproductive tract had a significant influence on the early adaptation period in newborns. Multifactorial colonization of the reproductive tract was associated with an increased incidence of infections in newborns and a higher prevalence of acid–base balance disorders. This study highlights the importance of monitoring and addressing the microbial composition of the reproductive tract during pregnancy. Full article