Dimeric peptoids as antibacterial agents.

Building upon our previous study on peptoid-based antibacterials which showed good activity against Gram-positive bacteria only, herein we report the synthesis of 34 dimeric peptoid compounds and the investigation of their activity against Gram-positive and Gram-negative pathogens. The newly designed peptoids feature a di-hydrophobic moiety incorporating phenyl, bromo-phenyl, and naphthyl groups, combined with variable lengths of cationic units such as amino and guanidine groups. The study also underscores the pivotal interplay between hydrophobicity and cationicity in optimizing efficacy against specific bacteria. The bromophenyl dimeric guanidinium peptoid compound 10j showed excellent activity against S. aureus 38 and E. coli K12 with MIC of 0.8 µg mL-1 and 6.2 µg mL-1, respectively. Further investigation into the mechanism of action revealed that the antibacterial effect might be attributed to the disruption of bacterial cell membranes, as suggested by tethered bilayer lipid membranes (tBLMs) and cytoplasmic membrane permeability studies. Notably, these promising antibacterial agents exhibited negligible toxicity against mammalian red blood cells. Additionally, the study explored the potential of 12 active compounds to disrupt established biofilms of S. aureus 38. The most effective biofilm disruptors were ethyl and octyl-naphthyl guanidinium peptoids (10c and 10 k). These compounds 10c and 10 k disrupted the established biofilms of S. aureus 38 with 51 % at 4x MIC (MIC = 17.6 µg mL-1 and 11.2 µg mL-1) and 56 %-58 % at 8x MIC (MIC = 35.2 µg mL-1 and 22.4 µg mL-1) respectively. Overall, this research contributes insights into the design principles of cationic dimeric peptoids and their antibacterial activity, with implications for the development of new antibacterial compounds.

Intestinal Carriage of Extended-Spectrum ß-Lactamase- (ESBL-) Possessing Escherichia coli and Klebsiella Species among Nepalese Health Science and Non-Health Science Students.

Infections due to extended-spectrum ß-lactamase- (ESBL-) producing Gram-negative bacteria have led to increased mortality, morbidity, and economic burden worldwide. These bacteria can colonize the healthy intestine of human beings and can disseminate in communities and hospital. This study aimed to investigate the prevalence of fecal carriage of ESBL-producing Escherichia coli and Klebsiella species among health science (HS) and non-health science (NHS) students. This descriptive cross-sectional study was conducted on 104 HS and 104 NHS students in which one stool sample from each student was collected and processed for bacterial culture and sensitivity testing according to standard bacteriological procedures. Each morphotype was identified and characterized phenotypically. The antimicrobial sensitivity profile of bacterial isolates was determined by the Kirby-Bauer disk diffusion technique. ESBL production was tested by combination disk method as recommended by the Clinical and Laboratory Standards Institute. Out of 208 stool samples, E. coli and Klebsiella spp. were recovered from 203 (86.8%) and 31 (13.2%) stool samples, respectively. Among those 234 isolates, 69 were positive for ESBL which included E. coli (n = 66, 95.7%) and Klebsiella spp. (n = 3, 4.3%). Fifty (42.4%) out of 118 isolates from HS students and 19 (16.4%) out of 116 from NHS students were colonized by ESBL-producers. Compared to non-ESBL producers, a higher number of ESBL-producing isolates were resistant to ciprofloxacin (14.5% vs. 1.8%, p < 0.001), cotrimoxazole (59.4% vs. 16.4%, p < 0.001), and amikacin (10.1% vs 4.2%, p < 0.001). All E. coli and Klebsiella species isolates were susceptible to meropenem. The prevalence of fecal carriage of ESBL-producing bacteria was higher in HS students; however, there was a considerable number of these strains colonizing NHS students as well. This "iceberg phenomenon" of asymptomatic carriage of ESBL-producing pathogens might act as a source of infection in both the community and hospitals. Therefore, surveillance of carriage of drug-resistant bacteria should be performed regularly.

A Novel 6'-N-Aminoglycoside Acetyltransferase, AAC(6')-Ial, from a Clinical Isolate of Serratia marcescens.

Serratia marcescens IOMTU115 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Ial. The encoded protein AAC(6')-Ial has 146 amino acids, with 91.8% identity to the amino acid sequence of AAC(6')-Ic in S. marcescens SM16 and 97.3% identity to the amino acid sequence of AAC(6')-Iap in S. marcescens WW4. The minimum inhibitory concentrations of aminoglycosides for Escherichia coli expressing AAC(6')-Ial were similar to those for E. coli expressing AAC(6')-Ic or AAC(6')-Iap. Thin-layer chromatography showed that AAC(6')-Ial, AAC(6')-Ic, or AAC(6')-Iap acetylated all the aminoglycosides tested, except for apramycin, gentamicin, and lividomycin. Kinetics assays revealed that AAC(6')-Ial is a functional acetyltransferase against aminoglycosides. The aac(6')-Ial gene was located on chromosomal DNA.

Identification of a novel 6'-N-aminoglycoside acetyltransferase, AAC(6')-Iak, from a multidrug-resistant clinical isolate of Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia IOMTU250 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Iak. The encoded protein, AAC(6')-Iak, consists of 153 amino acids and has 86.3% identity to AAC(6')-Iz. Escherichia coli transformed with a plasmid containing aac(6')-Iak exhibited decreased susceptibility to arbekacin, dibekacin, neomycin, netilmicin, sisomicin, and tobramycin. Thin-layer chromatography showed that AAC(6')-Iak acetylated amikacin, arbekacin, dibekacin, isepamicin, kanamycin, neomycin, netilmicin, sisomicin, and tobramycin but not apramycin, gentamicin, or lividomycin.

Fact-finding Survey of Nosocomial Infection Control in Hospitals in Kathmandu, Nepal-A Basis for Improvement.

The purpose of this study was to investigate the actual conditions of nosocomial infection control in Kathmandu City, Nepal as a basis for the possible contribution to its improvement. The survey was conducted at 17 hospitals and the methods included a questionnaire, site visits and interviews. Nine hospitals had manuals on nosocomial infection control, and seven had an infection control committee (ICC). The number of hospitals that met the required amount of personal protective equipment preparation was as follows: gowns (13), gloves (13), surgical masks (12). Six hospitals had carried out in-service training over the past one year, but seven hospitals responded that no staff had been trained. Eight hospitals were conducting surveillance based on the results of bacteriological testing. The major problems included inadequate management of ICC, insufficient training opportunities for hospital staff, and lack of essential equipment. Moreover, increasing bacterial resistance to antibiotics was recognized as a growing issue. In comparison with the results conducted in 2003 targeting five governmental hospitals, a steady improvement was observed, but further improvements are needed in terms of the provision of high quality medical care. Particularly, dissemination of appropriate manuals, enhancement of basic techniques, and strengthening of the infection control system should be given priority.

Distribution of antibody titer against Salmonella enterica among healthy individuals in nepal.

BACKGROUND: Enteric fever is an endemic problem in Nepal and Widal agglutination test is widely used for its diagnosis but a normal baseline titer in healthy population and cutoff values have not been established. METHODS: We measured average baseline antibody titers against "O" and "H" antigens of Salmonella enterica serotype Typhi and "H" antigens of serotypes Paratyphi A and Paratyphi B among apparently healthy blood donors in Nepal. The antibody titers were measured using Standard Widal Confirmatory Quantitative Tube test. RESULTS: Among the 100 blood samples collected from healthy volunteers, 62 individuals had significant antibody titers (> or = 1:20) against one of the four antigens against S. enterica. Among 54 samples with an anti-O titer against serotype Typhi, 15 and 36 samples had titers of > or = 1:60 and > or = 1:40, respectively. A significant proportion (12% of all) had anti-O titer of > or = 1:80. Similarly, among the 59 samples demonstrating anti-H titers of > or = 1:20 to S. enterica serotype Typhi, 29 had a titer of > or = 1:80 and 12 had 1:160. For S. enterica serotypes Paratyphi A and B, anti-H titers of > or = 1:20 were found only in 12% and 3%, respectively, of all samples tested. CONCLUSION: When a single Widal agglutination titer is used for the diagnosis of enteric fever, it will be more appropriate to change the currently used cutoff levels against S. enterica serotype Typhi to > 1:80 for anti-O and > 1:160 for anti-H titers for Nepal.

Multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing Salmonella enterica (serotypes Typhi and Paratyphi A) from blood isolates in Nepal: surveillance of resistance and a search for newer alternatives.

OBJECTIVES: We evaluated the prevalence of multidrug resistance (MDR) and production of extended spectrum beta-lactamase (ESBL) by Salmonella enterica (serotypes Typhi and Paratyphi A) in a teaching hospital in Nepal. The MDR strains of S. enterica were also tested for susceptibility to newer antibiotics. METHODS: Blood cultures were obtained from 4105 patients with febrile illnesses. Isolates of S. enterica were serotyped and antibiotic susceptibility testing was carried out using disk diffusion (Kirby-Bauer) and E-tests. ESBL screening and phenotype confirmation were done following National Committee for Clinical Laboratory Standards (NCCLS) recommendations for Escherichia coli. RESULTS: A total of 541 isolates of S. enterica serotypes Typhi (47%) and Paratyphi A (53%) were grown. Twenty-eight isolates (5%) of S. enterica were resistant to two or more antibiotics (MDR isolates), with a greater prevalence among serotype Paratyphi A (7%). All ESBL producers (three isolates) were serotype Paratyphi A. Most of the MDR S. enterica showed reduced susceptibility to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, ofloxacin, and ciprofloxacin, and had good susceptibility to extended-spectrum cephalosporins and carbapenems. Among the fluoroquinolones, gatifloxacin demonstrated better in vitro activity compared to levofloxacin, ciprofloxacin, and ofloxacin. CONCLUSIONS: A greater prevalence of S. enterica serotype Paratyphi A with higher rates of multidrug resistance and ESBL production is concerning for natives as well as travelers in Nepal since the current typhoid vaccines do not provide protection against this serotype.