Robinsoniella species are strictly anaerobic, Gram-positive, spore-forming bacilli infrequently associated with human bloodstream infections. We present a case of a 49-year-old woman with a history of colon and anal carcinoma treated with radiation and chemotherapy. She presented with fever, dyspnea, and worsening diarrhea. Blood cultures grew Serratia marcescens, Robinsoniella species, and Clostridium species, and she was initially treated with intravenous piperacillin-tazobactam and vancomycin, followed by cefepime, before ultimately transitioning to ertapenem. Although no treatment is currently established for Robinsoniella peoriensis, evidence remains insufficient to define an optimal antimicrobial regimen. This case highlights the pathogenic potential of Robinsoniella species in immunocompromised patients and underscores the importance of considering gastrointestinal pathology as a source of bacteremia involving this uncommon anaerobic organism.

Acinetobacter baumannii is a critical opportunistic pathogen responsible for a global health crisis, driven primarily by the rising prevalence of multidrug-resistant (MDR) strains. A central mechanism of β-lactam resistance in A. baumannii involves the overexpression of the class C β-lactamase AmpC, which degrades a wide spectrum of β-lactams, thereby limiting the effectiveness of antibiotics. The precise structural factors that dictate AmpC inhibition, however, have been less extensively studied and present opportunities to develop effective inhibitors against it. We explored natural inhibitors targeting the AmpC β-lactamase with an inclusive structure-based approach for drug discovery. Using an integrated computational methodology comprising molecular docking, pharmacokinetic analyses, and long-time MD simulations, a dataset of 374 phytocompounds was docked with AutoDock Vina. Among them, the phytocompounds 1521_0134 and N105_0095 with estimated binding affinities of -6.69 and -7.07 kcal/mol were identified as significant binding candidates. The detailed binding-mode analysis showed that both phytocompounds form strong, stable hydrogen bonds with key catalytic residues in the AmpC active pocket and have docking scores comparable to cefepime (binding energy of -7.48 kcal/mol), a well-known substrate for the AmpC β-lactamase. Additional SwissADME, pkCSM, and ProTox-3.0 analysis indicated promising drug-like properties for both phytocompounds with appropriate molecular weight, optimal lipophilicity, and good membrane permeability. We further performed 1000 ns all-atom MD simulations of AmpC in the presence of the top two phytocompounds to elucidate the dynamics and structural stability following ligand binding. Trajectory analyses demonstrated that ligand binding enhanced the structural stability of AmpC, as evidenced by reduced conformational fluctuations and restricted protein mobility. Principal component analysis (PCA) and free-energy landscape (FEL) analyses further indicated that the AmpC-ligand complexes were restricted within the stable conformational space throughout the simulations. Notably, the AmpC_1521_0134 complex presented two distinct free-energy basins, demonstrating structurally stable, thermodynamically controlled conformational ensembles. Moreover, the dynamic cross-correlation matrix (DCCM) analysis showed a decrease in correlated motion between remote residues, indicating the structural rigidity of the enzyme-ligand complexes. Collectively, our results provided a structural and energetic rationale for the interaction of natural phytocompounds with AmpC β-lactamase, with phytocompound 1521_0134 as a lead candidate that merits further development for the rational design of novel lactamase inhibitors to overcome multidrug-resistant A. baumannii.

Cefepime is used in critically ill pneumonia patients, but dosing in renal replacement therapy (RRT) is complicated by altered renal function, extracorporeal removal, and variability in pulmonary epithelial lining fluid (ELF) exposure. We sought to develop an integrated model linking systemic, extracorporeal, and pulmonary cefepime pharmacokinetics in RRT. Pharmacokinetic (PK) data from critically ill adults receiving cefepime and requiring RRT were included. In a dedicated continuous RRT (CRRT) cohort (n = 8), pre- and post-filter plasma and effluent PK data were collected. Additional patients (n = 43) requiring RRT also contributed plasma and ELF samples. A non-parametric population PK model was developed using an 80/20 subject-level development-validation split. Covariate models assessed the impact of residual renal function, effluent flow rate, body size, and fixed intradialytic hemodialysis (HD) clearance. Monte Carlo simulations evaluated plasma and ELF target attainment across dosing strategies, weight strata, and minimum inhibitory concentrations (MICs). The final model jointly described systemic, extracorporeal, and pulmonary cefepime disposition using piecewise central volume, native clearance, linear effluent-flow-dependent CRRT clearance, fixed HD clearance, and ELF distribution. Simulations showed adequate plasma target attainment, whereas ELF attainment was sensitive to MIC, target, regimen, and body weight. Continuous infusions of 4 g/day provided adequate ELF attainment at MICs ≤4 mg/L. Plasma-based cefepime target attainment may overestimate pulmonary exposure during RRT, particularly at higher MICs, body weights, and fT>MIC targets. External validation and prospective studies are needed to refine pulmonary target estimates and determine whether plasma-guided Bayesian dosing can reliably ensure site-of-infection exposure.

The emergence of extended-spectrum β-lactamase (ESBL) and mcr-1 genes in Escherichia coli (E. coli) in camel milk severely limits therapeutic options for treating multidrug-resistant bacterial infections. The present study focused on the prevalence, co-occurrence pattern, and antibiogram characteristics of ESBL and colistin-resistant E. coli isolated from milk samples of camels. Overall, 384 camel milk samples were collected aseptically and cultured for the isolation and confirmation of E. coli using standard microbiological procedures, followed by molecular confirmation. Phenotypic ESBL was assessed employing the combined disk diffusion method, while colistin resistance was determined through broth microdilution. Molecular detection of blaCTX-M, blaTEM, and mcr-1 genes was performed by PCR, followed by co-existence pattern and antibiogram analysis of ESBL and colistin-resistant E. coli isolates. Overall, E. coli was confirmed in 20.57% of milk samples. Among these isolates, 58.23% were phenotypically positive for ESBL, while 49.37% showed phenotypic resistance to colistin. The blaCTX-M, blaTEM, and mcr-1 genes were identified in 41.77%, 31.65%, and 26.58% of E. coli isolates, respectively. Co-occurrence of antimicrobial resistance genes revealed that blaTEM + blaCTX-M was detected in 12.66%, while blaTEM + mcr-1 genes were detected in 5.06% of isolates, and mcr-1 was detected alone in only 5.06% of isolates. Antibiogram analysis showed high resistance to amoxicillin, cefepime, and oxytetracycline. The findings of the current study highlight the importance of routine antimicrobial resistance surveillance and prudent antimicrobial use in camel production systems.

Salmonella enterica serovar Infantis is an emerging non-typhoidal Salmonella (NTS) serovar increasingly associated with foodborne gastroenteritis. Human infections caused by this serovar remain underreported in India. We report a case of acute gastroenteritis caused by Salmonella enterica serovar Infantis in a 53-year-old male from South India. The patient presented with acute-onset watery diarrhoea for six days associated with intermittent fever and recent outside food consumption. Stool culture yielded non-lactose fermenting colonies identified by automated identification using the VITEK-2 Compact system as Salmonella group, which was subsequently confirmed as Salmonella enterica serovar Infantis by the National Institute for Research in Bacterial Infections, Kolkata, India. Antimicrobial susceptibility testing revealed susceptibility to ceftriaxone, cefepime, carbapenems, ciprofloxacin, and trimethoprim/sulfamethoxazole, while resistance to aminoglycosides and cefuroxime-axetil was observed. The patient improved clinically with ceftriaxone therapy and supportive management. This case highlights the emerging clinical importance of S. Infantis in India and underscores the necessity of routine serotyping, antimicrobial susceptibility testing, and strengthened surveillance to monitor evolving resistance patterns and public health risks associated with NTS infections.