Armenia D, Alteri C, Micheli V
… +18 more, Allice T, Bonura C, Bruzzone B, Bon I, Corsini R, Zerbini A, Morelli L, Cerutti F, Giammanco G, Randazzo N, Bertoldi A, Novazzi F, Ibba G, Bertoli A, Bezenchek A, Ceccherini-Silberstein F, Zazzi M, Santoro MM
BACKGROUND: Monitoring HIV-1 subtype circulation and transmitted drug resistance (TDR) remains a key priority, particularly since the rollout of high-sensitivity next-generation sequencing (NGS). METHODS: Routine plasma...BACKGROUND: Monitoring HIV-1 subtype circulation and transmitted drug resistance (TDR) remains a key priority, particularly since the rollout of high-sensitivity next-generation sequencing (NGS). METHODS: Routine plasma HIV-1 RNA NGS genotyping data were collected from newly diagnosed individuals in Italy over 2022-24. HIV-1 TDR and genotypic susceptibility were evaluated through HIVdb with NGS set at 10% and 20%. Subtype and transmission clusters (TC) were determined through the maximum likelihood phylogeny based on the GTR + F + R9 model. RESULTS: Seven hundred and forty-two individuals were included, 51.9% harbouring non-B strains [CRF02_AG (18.1%); CRF BF (6.1%); A1/A3/A6 (7.1%); others (20.5%)]. TDR prevalence to any class was 11.7% at Sanger-like NGS-setting (>20%), slightly increased (15.0%) at 10% NGS-setting, and significantly varied across subtypes, with the highest prevalence observed in B subtype. Most antiretrovirals showed full genotypic activity in nearly 99% of individuals, except for efavirenz and rilpivirine (proportion of individuals with full activity <92%). A total of 57 TC were detected: 40 pairs, 17 clusters (>2 sequences). Thirteen TC (22.8%, 8 pairs, 5 clusters) involved individuals harbouring TDR. TDR was detected as minority mutations in five TC. CONCLUSIONS: A high proportion of HIV-1 non-B subtypes circulate in Italy. TDR prevalence is around 12% using NGS at Sanger-like threshold and moderately increases to 15% when NGS is set at 10%. However, the impact of the detected TDR on the susceptibility to currently used antiretrovirals in clinical practice is negligible.
Tarancon-Diez L, Lazaro-Martin B, Goicoechea-Martínez J
… +19 more, Domínguez-Romero R, Gómez Sirvent J, Garrote E, Minguell Domingo L, Cervantes-Hernández E, Gavilán C, Fortuny C, Bernardino JI, Diez C, Montero-Alonso M, Roca-Oporto C, Ocampo A, Jiménez AB, Rius N, López Segura N, Escosa-García L, Prieto L, Ramos JT, Navarro-Gomez ML
J Antimicrob Chemother
· 2026 Mar · PMID 41808664
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OBJECTIVES: ART has significantly improved survival among children, adolescents and young adults who acquired HIV perinatally or during early childhood (early-life acquired HIV, ELHIV). However, challenges persist, inclu...OBJECTIVES: ART has significantly improved survival among children, adolescents and young adults who acquired HIV perinatally or during early childhood (early-life acquired HIV, ELHIV). However, challenges persist, including virological failure (VF) and suboptimal immune recovery. This study aimed to describe clinical, virological and immunological outcomes of ELHIV individuals in Spain since 2020, and to identify factors associated with VF and impaired immune recovery. METHODS: A multicentre, retrospective cohort study was conducted using data from 642 ELHIV individuals actively followed in the CoRISpe and CoRISpe-FARO cohorts. Data included demographics, ART history, virological suppression (viral load ≤50 copies/mL), CD4/CD8 ratio and CDC immunological categories. Logistic regression identified factors influencing VF and immune progression. RESULTS: The median age of participants was 24 years, with 67.6% aged ≥18. Most (93.6%) acquired HIV via vertical transmission, with ART initiated at a median age of 1.93 years. At the time of analysis, 99.1% were on ART. Although 81.1% achieved virological suppression, 10.5% experienced VF, associated with PI-based regimens, independent of age, and a lower CD4 nadir. Immune recovery, defined as a CD4/CD8 ratio ≥1, was achieved by 52.3%. Impaired recovery was linked to older age at ART initiation and lower CD4 nadir, particularly among adolescents (12-18 years) and young adults. Children (<12 years) showed better immune profiles, with 97.8% achieving CD4 counts ≥500 cells/mm³. CONCLUSIONS: Early ART initiation and tailored interventions are essential to optimize outcomes in ELHIV populations. PI-based regimens were a risk factor for VF, whereas integrase strand transfer inhibitors appeared protective. Adolescents and young adults require targeted support to improve adherence and immune recovery, aligning with UNAIDS goals.
BACKGROUND AND OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) and NNRTIs are widely used in the treatment of HIV, but the real-world adverse events (AEs) profiles of these drugs remain inadequately characteriz...BACKGROUND AND OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) and NNRTIs are widely used in the treatment of HIV, but the real-world adverse events (AEs) profiles of these drugs remain inadequately characterized. We prioritized AEs reported with INSTIs and NNRTIs using data from the FDA Adverse Event Reporting System (FAERS). METHODS: Using FAERS data (from FDA approval to June 2024) for 10 drugs (cabotegravir, dolutegravir, raltegravir, elvitegravir, bictegravir, nevirapine, efavirenz, rilpivirine, doravirine and etravirine), we assessed AE clinical priority using a multi-criteria score. The score evaluated four criteria: clinical relevance, reporting proportion, case fatality rate and signal stability. We calculated reporting odds ratios (RORs) with 95% CIs; signals required the lower limit of 95% CIs of the ROR, ROR025 > 1 after Bonferroni correction across [N] tested AEs per drug. Events related to medication errors or HIV-related conditions were excluded. A case-by-case assessment was conducted to evaluate the confounding factors from co-medications and indications. RESULTS: We found 4487/6362 (70.5%) were low priority (0-2 points) and 1849/6362 (29.1%) were moderate (3-5 points), 2, 8, 6 and 15 marginally high-priority (≥4.5 points) adverse pregnancy outcomes were identified with dolutegravir, raltegravir, nevirapine, efavirenz, respectively; 26 AEs were high clinical priorities (>5 points). After case-by-case assessment, five noteworthy AEs remained. These included efavirenz-related haemolytic anaemia, etravirine-related hepatic failure, dolutegravir-related foetal death, raltegravir-related drug reaction with eosinophilia and systemic symptoms, and raltegravir-related hepatic failure. CONCLUSIONS: This study provides a systematic framework for evaluating post-marketing AEs of INSTIs and NNRTIs using a semi-quantitative scoring system. Our findings identified five high-priority AEs that require clinical validation and further investigation.
Abdul-Aziz MH, Cheng V, Burrows F
… +20 more, Buscher H, Cho YJ, Corley A, Diehl A, Gilder E, Kim HS, Levkovich BJ, Lim SY, Liu X, McGuinness S, Ordonez J, Parke R, Pellegrino V, Reynolds C, Rudham S, Wallis SC, Welch SA, Fraser JF, Shekar K, Roberts JA
OBJECTIVES: To describe meropenem population pharmacokinetics in critically ill adults receiving extracorporeal membrane oxygenation (ECMO) with or without renal replacement therapy (RRT), and to identify dosing regimens...OBJECTIVES: To describe meropenem population pharmacokinetics in critically ill adults receiving extracorporeal membrane oxygenation (ECMO) with or without renal replacement therapy (RRT), and to identify dosing regimens likely to achieve safe and effective exposures. METHODS: Serial blood samples were collected over a single dosing interval during ECMO. Total plasma concentrations were measured by a validated assay. Population pharmacokinetic modelling and Monte Carlo dosing simulations were performed using Monolix. Dosing regimens were assessed against efficacy targets (Cmin ≥2 or ≥8 mg/L) and a toxicity threshold (Cmin >45 mg/L). RESULTS: A total of 150 plasma concentration-time points were obtained from 18 patients. Meropenem pharmacokinetics were best described by a two-compartment model with first-order elimination. ECMO flow rate significantly influenced the volume of distribution of the central compartment, while estimated creatinine clearance and concomitant RRT significantly influenced drug clearance. Using the primary efficacy target of 2 mg/L, a meropenem dose of 1 g every 8 h as continuous infusion was the most appropriate regimen for patients with a creatinine clearance of 60-130 mL/min receiving ECMO at a flow rate of 4-6 L/min. In patients receiving RRT, this regimen demonstrated less than 4% probability of reaching toxic concentrations and 100% probability of achieving the efficacy target across all simulated scenarios. The regimen remained robust against the higher efficacy target of 8 mg/L in most scenarios. CONCLUSIONS: A meropenem dose of 1 g every 8 h as continuous infusion is safe and efficacious in most critically ill patients receiving ECMO with or without concomitant RRT.
Pauw HS, Schwarz R, Beij A
… +4 more, Sieswerda E, Voermans RP, van Santvoort HC, van Den Berg FF
J Antimicrob Chemother
· 2026 Mar · PMID 41808660
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Acute pancreatitis is among the most common gastrointestinal disorders requiring hospitalization and can be complicated by serious infections. Approximately 20% of patients progress to necrotizing pancreatitis, of whom ∼...Acute pancreatitis is among the most common gastrointestinal disorders requiring hospitalization and can be complicated by serious infections. Approximately 20% of patients progress to necrotizing pancreatitis, of whom ∼30% develop infected pancreatic necrosis, a complication associated with mortality rates of 15%-35% that often necessitates invasive interventions and intensive care treatment. Serious extra-pancreatic infections are also commonly reported in acute pancreatitis patients. This review summarizes current perspectives on antimicrobial therapy for infected pancreatic necrosis, with an emphasis on microbiology and pharmacokinetics. The microbiological spectrum found in infected pancreatic necrosis is predominantly enteric, reflecting translocation of gut flora into necrotic tissue, with Gram-negative bacteria such as Escherichia coli and Klebsiella spp. being most frequently isolated. Enterococci and Candida species are also commonly identified and have been associated with adverse outcome7444444s, while anaerobes are probably underreported due to inherent culture limitations and antibiotic use. Notably, prolonged hospitalization and cumulative antibiotic exposure select for antimicrobial-resistant and difficult-to-treat pathogens. On the basis of robust evidence, prophylactic antibiotics are not clinically effective in preventing infectious complications. Although carbapenems have traditionally been favoured for treatment of infected pancreatic necrosis on the basis of presumed superior tissue penetration, pharmacokinetic studies suggest that non-carbapenem beta-lactams such as piperacillin-tazobactam and cefepime may achieve adequate tissue penetration as well, particularly when administered as extended infusions. Comparative efficacy studies of antibiotic treatment strategies with clinical endpoints are needed.
Singhal A, Nurek M, Lau T
… +6 more, Mcentee J, Moore L, Mughal N, Mason S, Vizcaychipi M, Singh S
J Antimicrob Chemother
· 2026 Mar · PMID 41793742
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BACKGROUND: Point of care tests (POCTs) offer accurate rapid diagnostics for infection, but not reduced antibiotic overuse in antibiotic stewardship (ABS) studies. Prescribing behaviour shaped by clinical experience may...BACKGROUND: Point of care tests (POCTs) offer accurate rapid diagnostics for infection, but not reduced antibiotic overuse in antibiotic stewardship (ABS) studies. Prescribing behaviour shaped by clinical experience may influence antibiotic decisions more than test performance. Understanding prescribing behavioural differences may inform ABS education. OBJECTIVES: To find out whether antibiotic decision making differ among medical students and intensive care clinicians when offered POCT use. METHODS: An observational study depicted four simulated clinical vignettes of hospital acquired pneumonia. Clinicians and students decided to STOP or continue antibiotics, before and after a PCR-POCT result (negative for infection). Four clinico-biological (WBC/CRP) trajectories were tested: 'clinical-biological improvement', 'clinical improvement/biological worsening', 'clinical worsening/biological improvement' and 'clinical-biological worsening'. STOP decisions, POCT requests and willingness to stop antibiotics were compared between groups using Chi-squared analysis, Wilcoxon-rank and logistic regression analyses. RESULTS: Eighty-eight students and 70 clinicians participated. Pre-POCT, students stopped antibiotics less than clinicians (42% versus 53%, P = 0.007); most markedly in 'clinical improvement/biological worsening' (36% versus 73%, P < 0.001). Both groups requested POCT equally (65% versus 67%, P = 0.65). Negative POCT results raised student STOP rates to those of clinicians (70% versus 67%, P = 0.466); the greatest rise being in 'clinical improvement/biological worsening' (P = 0.006). CONCLUSIONS: Infection-detecting POCTs (negative) improved students' antibiotic stop rates to the level of clinicians, particularly in cases of clinico-biological ambiguity. A requested and negative POCT result can reduce (over)cautious prescribing, especially with ambiguous trajectories. Such simulated clinical infection vignettes offer a learning tool to improve antimicrobial judgement, and confidence in POCT driven decision making.
Schönenberger CM, Haenggi K, Ringera IK
… +18 more, Luoga E, Bresser M, Mothobi B, Mokhele K, Sando D, Molatelle M, Thahane L, Mnzava D, Ndege R, Hlasoa MM, Kayembe BP, Muhairwe J, Glass TR, Klimkait T, Weisser M, Labhardt ND, Tschumi N, Brown JA
J Antimicrob Chemother
· 2026 Mar · PMID 41793741
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BACKGROUND: Children and adolescents with HIV have lower treatment success than adults. Suboptimal adherence and resistance to antiretroviral therapy (ART) are known aetiological factors. This preplanned analysis in the...BACKGROUND: Children and adolescents with HIV have lower treatment success than adults. Suboptimal adherence and resistance to antiretroviral therapy (ART) are known aetiological factors. This preplanned analysis in the GIVE MOVE trial (NCT04233242) describes drug resistance patterns in children and adolescents in Lesotho and Tanzania. MATERIALS AND METHODS: GIVE MOVE randomized children and adolescents (6 months to below 19 years) with recent viraemia whilst taking ART to genotypic resistance testing (GRT)-informed care or usual care. Here, we conducted additional post-hoc GRT on stored samples from both groups and included participants with at least one successful resistance test. We assessed the number of drugs predicted to be active in participants' three-drug ART regimens and resistance-associated mutations. RESULTS: Amongst 137 participants, the majority were female (58%) and lived in Lesotho (77%). At their initial GRT, 69/137 (50%) were receiving protease inhibitor-based, 59/137 (43%) dolutegravir-based and 9/137 (7%) efavirenz-based ART. At that time, 80/137 (58%) participants had three, whilst 8/137 (6%) had two, 36/137 (26%) had one and 13/137 (9%) had no drugs predicted to be active in their regimens. Seventeen (12%) participants had resistance against their ART core agent, including one with high-level dolutegravir resistance.Across 312 detected resistance-associated mutations (222 major, 90 accessory), 146 conferred resistance to non-nucleoside reverse transcriptase inhibitors, 127 to nucleoside reverse transcriptase inhibitors, 28 to protease inhibitors and 11 to integrase strand transfer inhibitors. CONCLUSION: Given that more than half had an ART regimen predicted to be fully active, most viraemia in children and adolescents could not be explained by resistance.Registration: The GIVE MOVE trial was registered on Clinicaltrials.gov NCT04233242.
BACKGROUND AND OBJECTIVES: Cutibacterium species, including Cutibacterium avidum, Cutibacterium granulosum and Cutibacterium acnes are commensal skin bacteria. The latter exacerbates acne vulgaris. In the past decades, h...BACKGROUND AND OBJECTIVES: Cutibacterium species, including Cutibacterium avidum, Cutibacterium granulosum and Cutibacterium acnes are commensal skin bacteria. The latter exacerbates acne vulgaris. In the past decades, high antimicrobial use for the treatment of acne has led to the spread of macrolide- and lincosamide-resistant, particularly clindamycin-resistant, strains. C. avidum has been reported to show higher resistance rates than C. acnes. The known mechanisms of macrolide resistance in Cutibacterium species includes either mutations in 23S rRNA encoding gene or the acquisition of methyltransferase genes, such as erm(X) and erm(50). This study analysed the resistance mechanisms of C. avidum, a commensal skin species that is occasionally isolated from acne lesions. This study focused on strains lacking known macrolide-lincosamide resistance determinants. METHODS: The antimicrobial susceptibility of 50 C. avidum strains isolated from facial acne pustules between 2013 and 2020 was evaluated by determining MIC values. Whole-genome sequencing was used to identify the putative resistance factors. The candidate gene was cloned into Escherichia coli for functional analysis, and its amino acid sequence was compared with that of previously reported Erm proteins. RESULTS: Approximately 90% of C. avidum strains exhibited resistance to macrolides and clindamycin. Two of these strains lacked known resistance factors. Whole-genome sequence analysis revealed the presence of a methyltransferase-encoding gene. Introducing this gene into E. coli conferred resistance to macrolides, confirming its function. The protein with the highest similarity to Erm(38), but <79% identity, was therefore designated as Erm(57). Unlike erm(X) and erm(50), erm(57) was not transmitted horizontally. CONCLUSIONS: This study identified erm(57) as a novel non-transmissible macrolide-lincosamide resistance gene in C. avidum.
Pavia K, Day ME, Hambrick HR
… +5 more, Sibilia A, Fenchel M, Paice K, Kaplan J, Tang Girdwood S
J Antimicrob Chemother
· 2026 Mar · PMID 41793739
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BACKGROUND AND OBJECTIVE: Cefepime-induced neurotoxicity (CIN) is a recognized side effect of excessive cefepime exposure and high plasma concentrations in adults. However, the relationship between cefepime concentration...BACKGROUND AND OBJECTIVE: Cefepime-induced neurotoxicity (CIN) is a recognized side effect of excessive cefepime exposure and high plasma concentrations in adults. However, the relationship between cefepime concentrations and neurotoxic symptoms in paediatric patients is unknown. The objective of this paper is to explore the relationship between cefepime pharmacokinetics and CIN in a paediatric intensive care unit (PICU) cohort. PATIENTS AND METHODS: PICU patients with cefepime concentrations measured for a previous PK study were chosen for this cohort. CIN symptoms and related testing were evaluated by retrospective chart review and likelihood of causal association was determined using blinded adjudicators via the Naranjo adverse drug reaction probability scale. RESULTS: Among 73 patients with complete data, 43 patients (59%) had either no neurotoxicity or neurotoxicity doubtful to be CIN, while 25 (34%) patients had possible CIN and five (7%) had probable CIN. Symptoms of neurotoxicity included irritability, altered mental status, depressed level of consciousness, myoclonus, seizures and delirium. There were no differences in age, sex, severity of illness or renal dysfunction among groups. Patients with probable CIN had higher cefepime area under the curve (2250 versus 1107 mg*h/L, P = 0.03) and peak concentrations (232 versus 172 mg/L, P < 0.001). CONCLUSIONS: This investigation presents a paediatric cohort analysis of CIN and provides preliminary evidence supporting the hypothesis that neurotoxicity risk is probably concentration dependent in this age group and presents with similar spectrum of symptoms as those described in adults.
Invasive aspergillosis (IA) crude mortality has shown a sustained reduction over the past decades, demonstrated in randomized controlled clinical trials of new antifungal agents and across large population surveys. New d...Invasive aspergillosis (IA) crude mortality has shown a sustained reduction over the past decades, demonstrated in randomized controlled clinical trials of new antifungal agents and across large population surveys. New diagnostic tools and integrated management approaches have driven faster, more targeted initiation of appropriate antifungal therapy. In parallel, improvements in the identification of periods at highest risk for IA and in practices for management of the underlying disease processes predisposing to immunosuppression, including immunomodulatory therapies, have progressed. Given the highly complex and interconnected relationship between the underlying disease and its treatment and the predisposition to IA that the underlying disease creates, it is difficult to separate out which mortality improvements could be attributable to improved management of IA and which to better management of the underlying disease. The reductions in IA mortality have been sustained despite increases in the number of older, more vulnerable patients with more severe underlying disease undergoing treatment for acute haematological disorders and haematopoietic cell transplantation. This gradual and subtle move to a higher risk, more co-morbid patient population may have obscured any impact from the management developments other than antifungal therapy over this period, including better fungal diagnosis and supportive care. The overwhelming single factor contributing to a reduction in IA mortality over the past years appears to have been the routine adoption of mould-active antifungals, azoles in particular. Any impact of consensus definitions used to classify disease, improvements in diagnostic tools and earlier targeted strategies, remains difficult to measure based on available data. However, recently, the use of mould-active azoles has become threatened by the emergence of azole resistance in Aspergillus fumigatus, the frequent co-occurrence of Aspergillus species and Mucorales species, and difficult to handle drug-drug interactions, thereby fuelling an ongoing search for novel antifungal agents.
J Antimicrob Chemother
· 2026 Mar · PMID 41790510
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Biofilm-associated infections represent a major therapeutic challenge due to reduced antimicrobial susceptibility and the limited predictive value of conventional pharmacokinetic/pharmacodynamic (PK/PD) indices with clin...Biofilm-associated infections represent a major therapeutic challenge due to reduced antimicrobial susceptibility and the limited predictive value of conventional pharmacokinetic/pharmacodynamic (PK/PD) indices with clinical outcome. A wide spectrum of experimental models has been developed to study biofilms, ranging from simple in vitro assays to ex vivo tissue-derived systems and in vivo infection models. Each category provides distinct advantages: in vitro platforms enable high-throughput compound screening and measurement of biofilm-specific indices such as MBIC and MBEC; ex vivo models preserve host tissue architecture and allow investigation of topical therapies and therapeutic windows; and in vivo systems are indispensable for analysing host-pathogen interactions and systemic PK/PD relationships. No single model is sufficient to replicate clinical biofilm complexity, but combined use and progressive standardization can improve translational value. This review provides a structured overview of available models, their PK/PD readouts and their strengths and limitations, aiming to guide model selection in preclinical biofilm research and antimicrobial development.
BACKGROUND: Perioperative antibiotic prophylaxis is essential in oral cancer surgery to prevent surgical site infections, particularly when regional flaps such as the facial artery musculomucosal (FAMM) flap are used. Th...BACKGROUND: Perioperative antibiotic prophylaxis is essential in oral cancer surgery to prevent surgical site infections, particularly when regional flaps such as the facial artery musculomucosal (FAMM) flap are used. This study compared free cefuroxime concentrations in plasma, FAMM flap, buccal submucosa and subcutaneous tissue following bolus infusion (BI) versus continuous infusion (CI). METHODS: Eighteen patients scheduled for tumour resection and FAMM flap reconstruction were randomized to receive cefuroxime either as BI (1500 mg every 8 h) (Group BI) or CI (4500 mg/day) (Group CI). Microdialysis catheters were placed in the FAMM flap, buccal submucosa and subcutaneous tissue in the neck. Free cefuroxime concentrations were measured over 8 h. The primary endpoints were time with concentrations above the minimal inhibitory concentration (T > MIC) and attainment of the treatment target 50%T > MIC for MIC 2 and 4 mg/L. RESULTS: All patients achieved ≥50%T > MIC in all tissues for both MIC targets. Group CI achieved 100%T > MIC across all compartments and both MIC thresholds, whereas the mean T > MIC in Group BI were in the range 89%-98% for MIC 2 mg/L and 79%-90% for MIC 4 mg/L. Group CI achieved significantly higher T > MIC than Group BI in subcutaneous tissue for both MIC thresholds and in plasma for MIC 4 mg/L. CONCLUSIONS: A daily dose of 4500 mg cefuroxime provides adequate tissue and plasma concentrations with both BI and CI to achieve ≥50%T > MIC in patients undergoing oral cavity cancer surgery with FAMM flap reconstruction. CI provided more consistent exposure and may offer pharmacokinetic advantages in selected high-risk situations/patients.
Raguram KH, Sidhu M, Omrani MA
… +5 more, Baskaran BS, Chalabianloo N, Chhabra M, Sampasa-Kanyinga H, Muanda FT
J Antimicrob Chemother
· 2026 Mar · PMID 41790508
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BACKGROUND AND OBJECTIVES: Fluoroquinolones are linked with increased risk of CNS adverse events, such as anxiety and depression. Recently, case reports have linked fluoroquinolone use and panic attacks. However, current...BACKGROUND AND OBJECTIVES: Fluoroquinolones are linked with increased risk of CNS adverse events, such as anxiety and depression. Recently, case reports have linked fluoroquinolone use and panic attacks. However, current evidence exploring the link between fluoroquinolone use and panic attacks remains limited and requires investigation for safe use. To systematically review the literature on fluoroquinolone use and the risk of panic attacks, and to study this association by comparing fluoroquinolones with other antibiotics using the FDA Adverse Event Reporting System (FAERS) database. METHODS: MEDLINE and Embase databases were searched to identify relevant studies for systematic review. Active-comparator restricted disproportionality analyses using FAERS (2004Q1-2024Q4) were performed for ciprofloxacin, levofloxacin, and moxifloxacin compared to azithromycin and trimethoprim/sulfamethoxazole. Reporting odds ratios (ROR), proportional reporting ratios, adjusted ROR for potential confounders, and Bayesian analyses were conducted to detect safety signals for MedDRA term 'panic attack'. RESULTS: The systematic review identified 12 studies (4 clinical trials, 8 publications describing 11 case reports), with the prevalence of panic attacks ranging between 0.46% and 1.76% in trials. Disproportionality analysis showed that, compared to azithromycin, fluoroquinolones were associated with a 6-fold increase in reports of panic attacks and a 12-fold increase compared to trimethoprim/sulfamethoxazole. Results were consistent across Bayesian analyses. CONCLUSION: The findings suggest an association between fluoroquinolones and increased risk of panic attacks, underscoring the need for validation through pharmacoepidemiological studies. Due to reliance on spontaneous reports, causal relationships cannot be determined for clinical recommendations. These results offer insights for research on CNS safety profiles of fluoroquinolones.
Graziani L, Giani T, Farese A
… +7 more, Di Lauria N, Mantengoli E, Riccobono E, Rossolini GM, Bartoloni A, Spinicci M, ICare Study Group
J Antimicrob Chemother
· 2026 Mar · PMID 41790115
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OBJECTIVES: To report on clinical outcomes associated with vancomycin-resistant Enterococcus faecium (VRE) Bloodstream infections (BSIs) observed during a 6-year period at a hospital from an area of high VRE endemicity....OBJECTIVES: To report on clinical outcomes associated with vancomycin-resistant Enterococcus faecium (VRE) Bloodstream infections (BSIs) observed during a 6-year period at a hospital from an area of high VRE endemicity. MATERIAL AND METHODS: Retrospective study of patients with VRE and/or vancomycin-susceptible E. faecium (VSE) BSI in an Italian tertiary care hospital from January 2018 to December 2023. RESULTS: The cohort included 116 VRE and 225 VSE BSIs. The baseline characteristics were comparable in both populations. Almost half VRE population (53/116, 46%) received no or ineffective empiric therapy against VRE. A targeted effective therapy was initiated with a mean delay of 2.2, ± 0.4 days in the VRE patients and of 1.2 ± 0.1 days (P < 0.01) in the VSE patients. The univariate analysis showed higher rates of septic shock in the VRE group (60% versus 40%, P < 0.01), and the 30-day mortality rate was 29% and 46% in VSE and VRE BSIs, respectively (P < 0.01). By multivariate analysis, Sequential Organ Failure Assessment score (HR 1.25; 95% CI 1.19-1.31, P < 0.001), Charlson Comorbidity Index (HR 1.14; 95% CI 1.06-1.22, P = 0.001) and vancomycin resistance (HR 1.93; 95% CI 1.33-2.82, P = 0.001) resulted as independent predictors of mortality. The statistical association was confirmed in a sensitive analysis after removing polymicrobial BSI. CONCLUSIONS: E. faecium BSIs confirmed to be associated with high mortality rate, especially in fragile patients. Moreover, vancomycin resistance is an independent mortality factor. Further studies are needed to identify patients at higher risk for E. faecium BSI.
Abduljalil H, Bartie K, Bal AM
… +4 more, Rautemaa-Richardson R, Williams C, Kean R, Ramage G
J Antimicrob Chemother
· 2026 Mar · PMID 41781815
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OBJECTIVES: We sought to evaluate the comparative activity of rezafungin compared with caspofungin and other antifungal classes against biofilms from a large clinical panel of Candida strains (n = 167). METHODS: Biofilm...OBJECTIVES: We sought to evaluate the comparative activity of rezafungin compared with caspofungin and other antifungal classes against biofilms from a large clinical panel of Candida strains (n = 167). METHODS: Biofilm killing and inhibition were assessed using standard XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] metabolic assessment. Biofilm time-kill kinetics were also evaluated using metabolic and viable cell counts. Microscopy was performed to visually assess biofilm inhibition. RESULTS: Rezafungin was shown to outperform caspofungin and other antifungals against C. albicans, C. parapsilosis, C. tropicalis and Nakaseomyces glabratus (previously called C. glabrata) strains with a heterogeneous biofilm phenotype. Assessment of high biofilm-forming strains at 0.03 mg/L concentrations showed that rezafungin killed biofilms to an equal or greater extent than caspofungin. Time-kill studies showed a rapid reduction in metabolism and viable cfus by both rezafungin and caspofungin, but with little difference between both compounds. Evaluation of biofilm inhibition characteristics of both compounds showed that rezafungin was marginally more effective than caspofungin, which was corroborated by microscopical analyses. CONCLUSIONS: Together, these data show that rezafungin is non-inferior to caspofungin in terms of anti-biofilm activity and displays characteristics that suggest it can control biofilms more effectively than caspofungin. Further evaluation is required to establish whether these in vitro effects translate clinically, but the data indicate an opportunity for rezafungin to be used for the clinical management of biofilm-related diseases.
Frallonardo L, Guido G, De Gennaro N
… +8 more, De Iaco G, Signorile F, Cibelli M, De Luca A, Ritacco AI, Stolfa S, Di Gennaro F, Saracino A
J Antimicrob Chemother
· 2026 Mar · PMID 41781330
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BACKGROUND: Bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) remain associated with high mortality, even outside intensive care units (ICUs). Optimizing early β-lactam exposure through...BACKGROUND: Bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) remain associated with high mortality, even outside intensive care units (ICUs). Optimizing early β-lactam exposure through a loading dose (LD) of ceftazidime-avibactam or meropenem-vaborbactam may improve outcomes, but evidence in non-ICU settings is limited. METHODS: We conducted a retrospective single-centre study (January 2023-June 2025) including adult non-ICU inpatients with genotypically confirmed KPC-Kp BSI. The control group received standard dosing (ceftazidime-avibactam 2 g/0.5 g q8h or meropenem-vaborbactam 2 g/2 g q8h, both over 3 h). The LD group received either one standard dose infused over 30 min (Scheme A) or one standard dose + 50% infused over 2-3 h (Scheme B), followed by the standard regimen q8h. Primary outcomes were 7- and 30-day all-cause mortality; secondary outcomes included microbiological clearance ≤72 h, ICU transfer and/or vasopressor use, adverse events (AEs ≥ grade 2), hospital stay, and recurrence ≤30 days. RESULTS: A total of 189 patients were included (140 controls, 49 LD). Groups were comparable in age (median 74 years), comorbidities (Charlson 5), and renal function (eGFR ≈45 mL/min/1.73 m²). LD was associated with faster blood-culture clearance (78% versus 55%; RR 1.26, 95% CI 1.03-1.61, P = 0.02) and lower ICU/vasopressor requirement (7.5% versus 23%; RR 0.60, 95% CI 0.29-0.93, P = 0.02). Median hospital stay was shorter (33 versus 37 days, P = 0.3). Thirty-day mortality was lower in LD (16.3% versus 21.0%; adjusted RR 0.62, 95% CI 0.39-1.29, P = 0.23), indicating a non-significant but clinically relevant trend. No increase in adverse events or nephrotoxicity was observed. CONCLUSIONS: In non-ICU KPC-Kp BSIs, a β-lactam loading dose regimen was associated with faster microbiological clearance, reduced ICU transfer and shorter hospital stay, without added toxicity. Mortality showed a non-significant trend towards improvement. Pragmatic LD strategies may enhance early β-lactam exposure where therapeutic drug monitoring (TDM) is unavailable. Prospective PK/PD-guided studies are warranted.