Porins let drugs in, efflux pumps kick them out — alone, neither does much damage. Real resistance in Gram-negatives needs porin loss, efflux overexpression, and β-lactamases working together. Plus a ...

📊 Working through ROC-AUC from scratch, then poking at its blind spots — low prevalence, calibration, and finally Decision Curve Analysis. Mostly notes to myself on what I learned (and got confused by...

Take a closer look at this exceptional career opportunity, picture the impact you can make at Cleveland Clinic and apply to join us

Textbooks say LOOCV has the lowest bias but highest variance compared to 10 and 5-fold. Coded a K-Fold CV from scratch for learning to test that on simulated data 🔍📊 — and at n=1000 it holds up. At n=...

Generates balancing weights for causal effect estimation in observational studies with binary, multi-category, or continuous point or longitudinal treatments by easing and extending the functionality ...

This report describes two cases of Legionnaires disease associated with a hot tub at a rental property in New York.

Optimal cephalexin and cefadroxil dosing for skin and soft tissue infections (SSTIs) is unclear. We summarize clinical and pharmacokinetic/pharmacodynamic (PK/PD) data that compare dosing strategies ...

🧬 Back to basics! Learning non-polar amino acids, what zwitterions actually are, and dipping into the applied math — Rodrigues rotation and Lennard-Jones potential. Slowly building toward optimal phi/...

Facial palsy is one of many manifestations of Lyme borreliosis. Data from our 3- year retrospective descriptive cohort quality improvement study sugge…

The bacteria, which can cause more severe symptoms, have only been detected in the upper Midwest.

When researchers test whether an antibiotic will work, they usually do so in a controlled laboratory environment. But when an infection happens inside the human body, things aren't so clean and tidy.…

Exploring the CovR/S two-component system in Group A Strep 🧫 — from genome annotation with Bakta & BaktFold, to AlphaFold confidence metrics, and a first attempt at protein docking with Haddock3. Lear...

A note to myself on survival analysis — KM curves, log-rank tests & Cox models 🧮 If I wrote it the way I understood it, maybe I'll actually remember it 🤞

Tongue swabs are a promising alternative specimen for tuberculosis (TB) diagnosis. Although test specificity exceeds 98%, sensitivity is lower than sputum-based molecular testing. We investigated whether the use of tongue swabs could increase sample availability, resulting in similar diagnostic yield.MethodsIn this cross-sectional study (July 2024–January 2025), we screened consecutive people with presumptive TB at health centers in the Philippines, Vietnam, Uganda, and Zambia. Participants were asked to provide tongue swabs and referred for routine sputum collection. Tongue swabs were tested in research laboratories using the MiniDock MTB Test (Guangzhou Pluslife Biotech Co., Ltd., China); sputum was tested using WHO-recommended molecular testing per national guidelines. We compared diagnostic yield, defined as proportion of positive test results among all participants, between tongue swab- and sputum-based molecular testing with a prespecified 3.0% non-inferiority margin.ResultsOf 1639 participants, 851 (51.9%) were female, 415 (25.3%) were diagnosed with HIV, and 132 (8.1%) were children <5 years. All provided tongue swabs, but only 1389 (84.7%) produced sputum. Diagnostic yield was 3.8% (63/1639) for tongue swabs and 4.1% (68/1639) for sputum-based (68/1639, 4.1%) molecular testing. The difference (0.3%, 95% CI −0.6 to +1.2) was within the prespecified non-inferiority margin. Results were consistent across countries and key subgroups (age, sex, and HIV status).ConclusionsTongue swab-based molecular testing with MiniDock MTB achieved non-inferior diagnostic yield compared with sputum-based molecular testing. These findings support scale-up of swab-based platforms as a cost-efficient alternative, particularly where sputum collection is challenging or smear microscopy remains the primary diagnostic method.

Dipping my toes into quantum computing 🌊 — circuits, gates, superposition. Still very much a beginner, but hands-on experiments with qiskit + R's reticulate made it click a little more. Baby steps!

Join us for a session in the iDMentorship365 Webinar Series designed for residents and trainees exploring a career in Infectious Diseases. This webinar takes an in-depth look at the decision-making pr...

View abstract Objective:To evaluate the incidence, risk factors, and outcomes associated with multidrug-resistant organisms (MDROs) colonization in patients undergoing elective orthopedic surgery at the Thammasat University Hospital.Methods:We conducted a prospective MDROs surveillance screening (swabs from the nose, throat, groin, and rectum) in patients undergoing orthopedic surgery. MDROs were defined as extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria (GNB), carbapenem-resistant Enterobacterales, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. The incidence of MDROs colonization, risk factors, and outcomes including surgical site infections (SSIs) were assessed. Postoperative SSIs were compared between patients with and without MDROs colonization.Results:Of 384 swabs tested from 96 patients, ESBL-producing Escherichia coli was identified in 38 isolates (31 rectal swabs and 7 groin swabs) from 31 patients (32.3%). Only one patient had a history of admission within the previous year. Majority of procedures involved prosthetic implantation (77.1%) including total knee arthroplasty (30.2%). Seven patients (7.3%) developed SSIs without microbiological confirmation. The incidence of SSIs was higher among patients with ESBL-producing E. coli colonization compared to patients without colonization (6/31, 19.4% vs. 1/65, 1.5%; P = .004; odds ratio, 15.36; 95% CI 1.7–356.3). From the multivariate logistic regression analysis, preoperative ESBL-producing E. coli colonization was associated with SSIs (P = .014, adjusted odds ratio 16.53, 95% CI 1.78–153.44).Conclusion:Preoperative ESBL-producing E. coli colonization was common among patients undergoing orthopedic surgery and possibly increased risk of SSIs. Further studies for multidrug-resistant GNB screening, surgical outcomes, and antibiotic prophylaxis modification should be considered in endemic regions.

To celebrate 30 years of catching ’em all, discover the parallels between the Pokemon universe and our own.

Tuberculous meningitis (TBM), a severe form of extrapulmonary tuberculosis, requires sustained therapeutic drug concentrations in the central nervous system (CNS). Linezolid is a promising treatment for TBM due to excellent CNS penetration and bactericidal activity against Mycobacterium tuberculosis. However, co-administration with rifampicin may alter linezolid pharmacokinetics (PK), potentially reducing efficacy due to drug–drug interactions.MethodsWe utilized data from the Adjunctive Linezolid for the Treatment of TubERculous Meningitis trial, a phase II study evaluating high-dose (35 mg/kg) versus standard-dose (10 mg/kg) rifampicin, with or without linezolid, in adults with TBM. Plasma sampling occurred on days 1 (dense) and 14 (sparse) with cerebrospinal fluid (CSF) sampling. Population PK modeling and simulation were employed to characterize linezolid disposition in plasma and CSF.ResultsEighteen participants contributed 73 plasma and 30 CSF samples to the analysis. Plasma concentrations were best described by a 1-compartment model with linear absorption and clearance, linked to a CSF compartment. High-dose rifampicin increased linezolid clearance by 34.2%, reducing systemic and CNS exposure. Simulations demonstrated that 1200 mg once-daily dosing failed to maintain therapeutic plasma and CSF linezolid concentrations when co-administered with high-dose rifampicin. In contrast, 600 mg twice-daily achieved adequate linezolid exposures even with higher rifampicin doses.ConclusionsHigh-dose rifampicin significantly increases linezolid clearance, reducing plasma and CSF drug levels. However, twice-daily linezolid may mitigate this effect and maintain therapeutic concentrations. These findings underscore the importance of optimizing linezolid dosing when used with rifampicin in TBM and support evaluation in larger studies to guide treatment strategies.

Bloodstream infections (BSI) caused by metallo-beta-lactamase (MBL)-producing Enterobacterales (E) are associated with high mortality. However, in most Latin American countries there is a lack of clinical and microbiological data on BSI caused by MBL-E.MethodsThis preplanned subgroup analysis of the multicenter, observational, prospective EMBARCAR study focused on adult patients with BSI caused by MBL-E in Argentina. Logistic regression adjusted by propensity scores (PS) for the treatment with ceftazidime-avibactam plus aztreonam (CAZ/AVI plus ATM) were used to identify variables associated with mortality.ResultsA total of 140 patients with BSI caused by MBL-producing Enterobacterales were included. Median age was 59 years (IQR 46–70), and most patients were male (61%). Most frequent comorbidities were diabetes 23%, class III obesity 19%, and chronic renal failure 19%. Two thirds of patients were hospitalized in critical care units, 60% required mechanical ventilation and 38% presented with shock. Most frequent isolated microorganisms were Klebsiella pneumoniae (75%) and Serratia marcescens (12%). Most patients (64%) received combination therapy and 23% received CAZ/AVI plus ATM. Thirty-day mortality was 41%. In the multivariate PS adjusted analysis, INCREMENT-CPE score ≥8 was associated with increased risk of mortality (odds ratio [OR] 3.63; 95% CI: 1.13, 11.7), while CAZ/AVI plus ATM therapy with a lower risk of death (OR 0.18; 95% CI: .05, .58).ConclusionsIn summary, BSI due to MBL-producing Enterobacterales resulted in a high mortality rate in our country. The use of CAZ/AVI plus ATM was associated with a decreased mortality. Better access to these antibiotics should be granted.

Rémi Rouget, Nadia Valin, Antoine Bachelard, Christia Palacios, Amélie Chabrol, Antoine Faycal, Marc-Antoine Valantin, Valérie Pourcher, Jade Ghosn, Gilles

It remains unclear if cefazolin inoculum effect (CzIE) translates to poorer clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections who were treated with cefazolin.MethodsThis retrospective cohort study across five hospitals in Ontario, Canada from 2021 to 2025 included adult patients who received cefazolin treatment for serious MSSA infection based on blood or deep sterile site culture growth. CzIE was defined as a ≥4 fold increase in cefazolin minimum inhibitory concentration to ≥16 μg/mL at a high inoculum based on broth microdilution assay. Patients were followed to 90 days. Primary outcome was all-cause mortality. Secondary outcome was microbiological treatment failure based on culture growth of MSSA after one week of cefazolin treatment. Potential confounders were adjusted using propensity score weighting and a competing risk model for microbiological treatment failure was used to account for mortality as a competing event.ResultsOf 259 patients, 92 (35.5%) patients had an MSSA isolate that displayed CzIE. The 90-day mortality rate was 19/92 (20.7%) and 37/167 (22.2%) in the CzIE positive and negative group respectively with adjusted risk difference of 0.6% (95% CI -9.0% to 10.2%, p=0.9060). Microbiological treatment failure occurred in 19/92 (20.7%) and 10/167 (6.0%) from the CzIE positive and negative group respectively with adjusted sub-distribution hazard ratio of 3.12 (95% CI 1.38 to 7.08, p=0.0065) in a competing risk model.ConclusionsCzIE was associated with a significantly increased risk of microbiological treatment failure. CzIE testing may be useful in guiding antibiotic treatment for serious MSSA infections.

ABSTRACTHere, we developed and evaluated a filter-paper urine collection method for chlamydia and gonorrhea testing. Dried urine strips (DUS) were developed to fit into the sample collection tube used for high throughput Hologic Aptima Combo 2 assay, minimizing processing post-sample collection. Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) bacterial stock dilutions were used to assess DUS performance and long-term stability at different temperature conditions. DUS diagnostic performance was evaluated against urine samples with Aptima Combo 2 Assay and an in-house RT-PCR method for CT and NG detection utilizing residual diagnostic urine specimens (n = 60 CT and NG negative, n = 50 CT-positive and n = 55 NG-positive, including 5 CT/NG dual-positive). Replacing the overnight strip drying step with use of additional desiccants was evaluated in order to reduce barriers to self-sample collection. We observed a high degree of diagnostic accuracy (>91% sensitivity and >98% specificity), compared to traditional urine samples across all evaluated DUS preparation and storage methods. DUS samples demonstrated high stability for prolonged periods at tested temperature storage conditions with some loss in sensitivity at lower bacterial loads. While drying of the sample was crucial to preserve sample integrity and improve recovery post-elution, placing the DUS directly into the sample storage bag with additional desiccants did not negatively impact diagnostic performance. DUS specimens were shown suitable for downstream CT genotyping and NG sequence typing. The developed DUS represents an accurate and stable sample collection method for CT and NG diagnostic testing and downstream pathogen characterization.IMPORTANCEInnovative sampling methods that are convenient, accurate, and user-friendly are crucial to increase sexually transmitted infection (STI) testing uptake. This study establishes a novel dried urine strip sample collection method for chlamydia and gonorrhea testing and downstream molecular characterization. Results show no inferiority of dried urine strips compared to urine, with regard to diagnostic performance, when analyzed using molecular in-house and commercial assays for chlamydia and gonorrhea detection. A dried urine strip sample collection method for chlamydia and gonorrhea testing offers significant advantages in resource-limited or stigmatized settings; it enables self-collection, mail-in return, and long-term storage at ambient temperatures, making it ideal for reaching underserved populations. The broader public health impact is the expansion of STI screening access and reduction in STI transmission by offering a discreet, scalable alternative to traditional specimen collection.

🦠 Made up my own memory tricks — Amp(G)atekeeper, Amp(D)umpster, Amp(R)epressor — to understand AmpC mechanics. Learnt Serratia has 2 recyclers (AmpD + AmiD2) making derepression harder, and E. coli l...

📊 Dipping my toes into financial statements — income, balance sheet & cash flow. Still don't fully get it, but slowly piecing together the story these numbers tell. Warren Buffett makes it look easy 😅...

ABSTRACTCarbapenem-resistant organisms (CROs) pose a major threat to global health due to limited therapeutic options and their capacity for rapid dissemination. Among these, carbapenemase-producing (CP) strains are of greatest concern, as they hydrolyze most β-lactams, and carbapenemase genes are readily spread via mobile genetic elements. Historically, clinical laboratories relied solely on minimal inhibitory concentration (MIC) results and interpretive criteria to guide therapy, with carbapenemase testing performed mainly for epidemiologic purposes. However, changing carbapenemase epidemiology, the introduction of enzyme-specific novel β-lactam combination agents for treatment, and updated Clinical and Laboratory Standards Institute (CLSI) guidance have renewed the importance of carbapenemase testing among carbapenem-resistant Enterobacterales. The 2025 CLSI M100 update now recommends carbapenemase testing for most Enterobacterales resistant to at least one carbapenem, emphasizing differentiation of key enzymes, such as KPC, NDM, and OXA-48-like, to inform therapeutic decisions and support antimicrobial stewardship. This minireview summarizes the evolution of CLSI guidance from early breakpoint establishment through the “MIC-only” era to the current antimicrobial resistance mechanism-driven framework. Key issues addressed include the clinical limitations of prior clinical breakpoints, challenges in balancing sensitivity and specificity of screening criteria to guide carbapenemase testing in different settings, and the expanding role of rapid phenotypic and molecular detection methods. Revisions to the EDTA-modified carbapenem inactivation method (eCIM) are discussed in light of increasing co-production of metallo-beta-lactamase and serine-carbapenemases. Reintegration of carbapenemase testing into clinical workflows highlights the role of the clinical microbiology laboratory as a critical component of antimicrobial stewardship.

Exploring pip/tazo PTA for Pseudomonas using popPK simulation. Key finds: 30-min infusions fall short of 90% PTA at MIC 16; prolonged infusion helps, but neutropenic fever population sees the biggest ...

🧪 Diving into PK/PD for the first time — simulating ceftriaxone with mrgsolve in R. Free drug levels were... surprisingly high? Even pushed it to q48h dosing out of curiosity and the results left me w...

Learnt major carbapenemase genes (KPC, NDM, OXA) using NCBI isolate data and molecular dynamics. Includes gene frequency trends, co-resistance patterns, and MM/PBSA binding comparisons of avibactam wi...

🧬 Testing beta-lactamase resistance with AlphaFold + DiffDock + GROMACS! Watch clavulanic acid bind TEM-5, CTX-M-15, KPC-2, and get rejected by TEM-30. Simulation confirms biology! 🔬💊

🧬 Explored molecular docking & MD simulations with penicillin binding to PBP2x — lots of stumbling through GROMACS but slowly piecing it together! 💊 Still much more to learn, but we're getting there! ...

Antibiotic resistance is a threat to public health driven in part by widespread antibiotic administration. Days of antibiotic spectrum coverage (DASC) is a novel metric to quantify both duration and breadth of antibiotic exposure that has not previously been used as an endpoint in a clinical trial. We calculated DASC using data from the Ceftriaxone to Prevent Pneumonia and Inflammation after Cardiac Arrest (PROTECT) trial to determine the association of ceftriaxone prophylaxis with DASC and with the acquisition of antibiotic resistance genes (ARGs).MethodsPROTECT randomized out-of-hospital cardiac arrest subjects to ceftriaxone or placebo for 3 days. ARGs were measured from rectal swabs collected at Days 0, 3 and 7 post randomization. DASC was calculated for each subject and compared using a two-sided Mann–Whitney U-test. Correlations between DASC and new ARGs, antibiotic-free days (AFD) and days of therapy (DOT) were tested using Kendall’s tau-alpha.ResultsPROTECT enrolled 52 subjects, 26 per treatment group, and treatment groups were similar at baseline. Median DASC scores were lower in the ceftriaxone group (19.5; IQR: 0, 43) compared with placebo (53; IQR: 16, 81). We found no correlation between DASC and new ARGs at either timepoint, or between DASC and AFD. DASC was correlated with DOT.ConclusionsDASC post intervention was lower in the ceftriaxone group, representing less antibiotic exposure following the intervention. There was no correlation between new ARGs and DASC. Further study is needed to understand the relationship between antibiotic prophylaxis, subsequent antibiotic exposure and resistome changes in the critically ill.

Enjoyed learning the process of setting up a cluster of tiny PCs for parallel computing. A note to myself on installing Ubuntu, passwordless SSH, automating package installation across nodes, distribu...

Testing Super Learner with TMLE showed some interesting patterns 🤔 XGBoost + random forest only hit ~54% coverage, but tuned xgboost + GLM reached ~90%. Seems like pairing flexible learners with stabl...

Clinical prediction scores such as NOVA and DENOVA aim to identify patients with enterococcal bacteremia at low risk of infective endocarditis (IE) in whom imaging might be safely avoided. The aim was to evaluate the performance of NOVA and DENOVA scores and to introduce a modified tool, DENOVi.MethodsThis retrospective study included adult patients with enterococcal bacteremia at two Swiss tertiary centers (2015–2024). IE was adjudicated by multidisciplinary Endocarditis Teams according to 2023 Duke-ISCVID criteria. Patients were stratified as high risk for IE using the adapted NOVA score (cut-off: ≥4), the DENOVA score (≥3), and a newly developed DENOVi score (≥2), which excluded the subjective murmur criterion and broadened “valve disease” to include intracardiac electronic devices (new Vi component).ResultsAmong 827 bacteremia episodes, 172 (21%) were diagnosed with IE. The adapted NOVA, DENOVA, and DENOVi scores classified 76%, 26%, and 42% of patients as high risk, respectively. Corresponding NLRs were 0.04 (95% CI, 0.01–0.15), 0.10 (0.06–0.16), and 0.04 (0.02–0.10). The adapted NOVA substantially increased the proportion of echocardiograms needed to be performed from 58% based on clinical evaluation alone to 76%, whereas the DENOVA and DENOVi scores would have reduced this proportion to 26% and 42% of episodes, respectively.ConclusionsBoth adapted NOVA and DENOVi scores reliably ruled out IE, but DENOVi provided the most balanced approach between diagnostic safety and resource utilization. DENOVi therefore represents a pragmatic and objective tool for IE risk stratification in enterococcal bacteremia. Prospective validation is warranted.

📚 Tried building Super Learner from scratch to understand what's happening under the hood. Walked through the NNLS algorithm step-by-step—turns out ensembling models may beat solo models! Our homegrow...

Fever accompanied by disseminated lymphadenopathy presents a significant diagnostic challenge. Our prior clinical observations indicated a high detection rate of Nocardia farcinica (N. farcinica) DNA in patients with this presentation. Kikuchi-Fujimoto disease (KFD) is a common cause in young adults with fever and lymphadenopathy, yet its etiological drivers remain largely unknown.ObjectiveThis dual-center study aimed to investigate the prevalence of N. farcinica infection in a pathologically confirmed KFD cohort, to analyze its correlation with clinical phenotypes, particularly systemic involvement, in comparison to Castleman disease (CD).MethodsFormalin-fixed, paraffin-embedded tissue specimens from 35 KFD and 18 CD patients were tested by N. farcinica-specific qPCR. Clinical and imaging data were reviewed for comparison.ResultsN. farcinica DNA was significantly more prevalent in KFD (51.4%) than in CD (5.6%) (P<0.001). Within KFD, positive patients were older, had a shorter onset-to-presentation interval, and exhibited more pronounced leukopenia (all P<0.05). A history of recent trauma (11.1% vs. 0%) and immunosuppression (5.6% vs. 0%) was exclusively documented in the N. farcinica-positive group, albeit in small number. Furthermore, N. farcinica-positive patients showed a higher, though not statistically significant, prevalence of bilateral lymph node involvement (72.2% vs. 52.9%, P=0.34) and a trend towards involvement of more nodal regions compared to negative counterparts.ConclusionThis study demonstrated a potential association between N. farcinica and KFD, suggesting a clinical subtype characterized by older age, shorter onset-to-presentation interval, and significant leukopenia. These findings offer novel etiological insights and suggest potential targeted therapeutic approaches, warranting validation through larger prospective studies.

The incidence of non-tuberculous mycobacterial (NTM) infections has been rising and now exceeds tuberculosis in several countries. Mycobacterium avium is the most common NTM cause of chronic lung disease. Current guidelines recommend simultaneous administration of three or more antibiotics, modeled after tuberculosis treatment, but these regimens are limited by toxicity, poor adherence, and low cure rates. Importantly, unlike M. tuberculosis, M. avium is acquired from the environment rather than transmitted between humans, weakening the rationale for multidrug therapy as necessary to suppress resistance.MethodsTo test an alternative treatment approach, we evaluated sequential monotherapy in a validated murine model of chronic M. avium lung infection. Mice were treated with either the standard triple-drug regimen of clarithromycin, ethambutol, and rifampicin or with sequential monotherapy: clarithromycin, bedaquiline, and clofazimine, with only one drug administered at a time for four-week intervals. Lung and spleen bacterial burdens were quantified, and minimum inhibitory concentrations (MICs) were determined for isolates recovered during treatment to assess resistance emergence.ResultsSequential monotherapy achieved reductions in lung bacterial burden equivalent to those of the standard multidrug regimen and prevented extrapulmonary dissemination. Notably, no increase in MICs was observed for clarithromycin, bedaquiline, or clofazimine across treatment phases, indicating that sequential monotherapy did not select for resistant clones.ConclusionsThese findings provide the first evidence that sequential monotherapy can deliver efficacy comparable to multidrug therapy for M. avium disease without promoting resistance. This proof-of-concept supports further investigation of sequencing strategies as a potentially more tolerable alternative to current triple-agent regimens.