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Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is of critical concern in healthcare settings, leading to limited treatment options. In this study, we conducted a comprehensive meta-analysis to assess the prevalence of CRAB by examining temporal, geographic, and bias-related variations. Methods: We systematically searched prominent databases, including Scopus, PubMed, Web of Science, and EMBASE. Quality assessment was performed using the JBI checklist. Subgroup analyses were performed based on the COVID-19 timeframes, years, countries, continents, and bias levels, antimicrobial susceptivity test method and guidelines. Results: Our comprehensive meta-analysis, which included 795 studies across 80 countries from 1995 to 2023, revealed a surge in carbapenem resistance among A. baumannii, imipenem (76.1%), meropenem (73.5%), doripenem (73.0%), ertapenem (83.7%), and carbapenems (74.3%). Temporally, 2020–2023 witnessed significant peaks, particularly in carbapenems (81.0%) and meropenem (80.7%), as confirmed by meta-regression, indicating a steady upward trend. Conclusion: This meta-analysis revealed an alarmingly high resistance rate to CRAB as a global challenge, emphasizing the urgent need for tailored interventions. Transparency, standardized methodologies, and collaboration are crucial for the accurate assessment and maintenance of carbapenem efficacy. [ABSTRACT FROM AUTHOR]

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays. [ABSTRACT FROM AUTHOR]

Multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Acinetobacter spp. present monumental global health challenges. These organisms represent model Gram-negative pathogens with known antibiotic resistance and biofilm-forming properties. Herein, a novel, nontoxic biocide, AB569, consisting of acidified nitrite (A-NO2-) and ethylenediaminetetraacetic acid (EDTA), demonstrated bactericidal activity against all Ab and Acinetobacter spp. strains, respectively. Average fractional inhibitory concentrations (FICs) of 0.25 mM EDTA plus 4 mM A-NO2- were observed across several clinical reference and multiple combat wound isolates from the Iraq/Afghanistan wars. Importantly, toxicity testing on human dermal fibroblasts (HDFa) revealed an upper toxicity limit of 3 mM EDTA plus 64 mM A-NO2-, and thus are in the therapeutic range for effective Ab and Acinetobacter spp. treatment. Following treatment of Ab strain ATCC 19606 with AB569, quantitative PCR analysis of selected genes products to be responsive to AB569 revealed up-regulation of iron regulated genes involved in siderophore production, siderophore biosynthesis non-ribosomal peptide synthetase module (SBNRPSM), and siderophore biosynthesis protein monooxygenase (SBPM) when compared to untreated organisms. Taken together, treating Ab infections with AB569 at inhibitory concentrations reveals the potential clinical application of preventing Ab from gaining an early growth advantage during infection followed by extensive bactericidal activity upon subsequent exposures. [ABSTRACT FROM AUTHOR]

Contaminated poultry meat is considered to be the main source of human infection with Campylobacter spp., a pathogen that asymptomatically colonizes broiler chickens during fattening and contaminates carcasses during slaughter. To prevent or reduce the colonization of broiler flocks with Campylobacter spp., applying different organic acids, especially in combinations, via feed or drinking water seems to be a promising approach. However, only very few combinations of organic acids have been tested for their antibacterial efficacy against Campylobacter spp. Therefore, the in vitro susceptibility of 30 Campylobacter spp. isolates (20 C. jejuni and ten C. coli) to ten organic acids and ten combinations was determined. The testing of minimum inhibitory concentration (MIC) values was performed at pH 6.0 and 7.3 by using the broth microdilution method and included the following organic acids: Caprylic acid, sorbic acid, caproic acid, benzoic acid, ascorbic acid, propionic acid, acetic acid, formic acid, fumaric acid and tartaric acid and combinations thereof. The lowest MIC values were seen for caprylic acid (MIC range at pH 7.3: 0.5–2 mmol/L) and sorbic acid (MIC range at pH 7.3: 1–4 mmol/L). One to two dilution steps lower MIC values were determined at the lower pH value of 6.0. Furthermore, ten combinations consisting of three to five organic acids were developed. In addition to the tested antibacterial activity, other criteria were included such as approval as feed additives, reported synergistic effects and chemical properties. For nine of ten combinations, the MIC90 values of the organic acids decreased 1.25- to 241.5-fold compared to the MIC90 values for the individual substances. Furthermore, nine of ten combinations exhibited synergistic activities against two or more of the tested C. jejuni and C. coli isolates. A combination of caprylic acid, sorbic acid and caproic acid exhibited synergistic activities against the largest number of Campylobacter spp. isolates (six C. jejuni and four C. coli) with fractional inhibitory concentration (FIC) indices (∑FIC) ranging from 0.33 to 1.42. This study shows in vitro synergistic activities of different organic acids in combinations against the major Campylobacter species and could therefore be a promising basis for reducing Campylobacter spp. in vivo. [ABSTRACT FROM AUTHOR]

Background: Given their geographical proximity but differences in cultural and religious dietary customs, we hypothesize that children from the three main ethnic populations (Han, Hui, and Tibetan) residing in the Qinghai–Tibetan Plateau region differs in their non-iatrogenic antibiotic loads. Methods: To determine the antibiotic burden of the school children unrelated to medical treatment, we quantified the antibiotic residues in morning urine samples from 92 Han, 72 Tibetan, and 85 Muslim Hui primary school children aged 8 to 12 years using high-performance liquid chromatography-tandem mass spectrometry, and performed correlation analysis between these data and concurrent dietary nutrition assessments. Results: Sixteen of the 18 targeted antibiotics (4 macrolides, 3 β-lactams, 2 tetracyclines, 4 quinolones, 3 sulfonamides, and 2 aminoanols) were identified in the urine samples with an overall detection frequency of 58.63%. The detection frequency of the six antibiotic classes ranged from 1.61% to 32.53% with ofloxacin showing the single highest frequency (18.47%). Paired comparison analysis revealed significant differences in antibiotic distribution frequency among groups, with Tibetans having higher enrofloxacin (P = 0.015) and oxytetracycline (P = 0.021) than Han children. Norfloxacin (a human/veterinary antibiotic) was significantly higher in the Hui children than in the Han children (P = 0.024). Dietary nutrient intake assessments were comparable among participants, showing adequate levels of essential vitamins and minerals across all three ethnic groups. However, significant differences in specific foods were observed among groups, notably in lower fat consumption in the Hui group. Conclusions: The introduction and accumulation of antibiotic residues in school children through non-iatrogenic routes (food or environmental sources) poses a serious potential health risk and merits closer scrutiny to determine the sources. While the exact sources of misused or overused antibiotics remains unclear, further study can potentially correlate ethnicity-specific dietary practices with the sources of contamination. [ABSTRACT FROM AUTHOR]

Introduction: The stethoscope, which is non-critical medical devices and a symbol of healthcare, is likely to be contaminated by pathogenic microorganisms and can play a contributory role in the transmission of hospital-acquired infection. And regular cleaning of the diaphragm of the stethoscope with a suitable disinfectant is decisive. However, in the resource-constrained setting like many healthcare facilities in Ethiopia healthcare provider’s stethoscope disinfection practice and its associated factors have not been well studied so far. Therefore, this study sought to determine stethoscope disinfection practice and associated factors among the healthcare providers in Addis Ababa, Ethiopia. Methods: A facility-based cross-sectional study was carried out between April and May 2016. For this study, 576 healthcare providers (physicians, health officers, nurses, midwives, and anesthesiologist) were included from 21 healthcare facilities in Addis Ababa. A pre-tested structured questionnaire was used for data collection. Descriptive statistics were computed. Bivariate and multivariable logistic regression analyses were used to identify factors that were significantly associated with stethoscope disinfection after every use. Results: A total of 546 healthcare providers participated in this study, for a response rate of 94.7%. Two-fifths, 39.7% (95%CI: 35.9, 44.0%) of healthcare providers disinfecting their stethoscope after every use. And a significant number of participants 34.6% (95%CI: 30.8, 38.5%) never disinfect their stethoscope. Three out of four (76.0%) healthcare providers believe that stethoscope contamination can contribute to the transmission of infections. Safe infection prevention practice (AOR = 3.79, 95%CI: 2.45–5.84), awareness on infection prevention guideline (AOR = 1.93; 95%CI: 1.31, 2.82), and favorable attitude towards infection prevention (AOR = 1.73, 95%CI: 1.02, 2.93) were significantly associated with stethoscope disinfection after every use. The study also found that the odds of stethoscope disinfection were likely to be reduced by 79% among physicians than nurses (AOR = 0.21; 95%CI: 0.09, 0.49). Conclusions: Only a small proportion of healthcare providers disinfect their stethoscopes after every use. Factors such as safe infection prevention practice, awareness on infection prevention guidelines, and favorable attitude towards infection prevention were the independent predictors of stethoscopes disinfection after every use. Hence, promotion of stethoscope hygiene along with an educational program to enhance disinfection compliance in healthcare facilities may have a positive effect. [ABSTRACT FROM AUTHOR]

Background: Mobile phones (MPs) have been an essential part of the lives of healthcare professionals and have improved communication, collaboration, and sharing of information. Nonetheless, the widespread use of MPs in hospitals has raised concerns of nosocomial infections, especially in areas requiring the highest hygienic standards such as operating rooms (ORs). This study evaluated the incidence of bacterial contamination of the MPs carried by medical staff working in the OR and determined its association with bacterial colonization of this personnel. Methods: This is an observational cohort study. Medical staffs working in the OR were asked to take bacterial cultures from their MPs, anterior nares, and dominant hands. To identify the relation between MP contamination and bacterial colonization of the medical staff, genotyping of Staphylococcus aureus (SA) was done via Staphylococcus protein A gene (spa) typing and pulsed-field gel electrophoresis (PFGE). Results: A total of 216 swab samples taken from 72 medical-staff members were analyzed. The culture-positive rate was 98.1% (212/216). In 59 (27.3%) samples, the bacteria were possible clinical pathogens. The anterior nares were the most common site of colonization by clinical pathogens (58.3%, 42/72), followed by MPs (13.9%, 10/72) and the dominant hand (9.7%, 7/72). SA was the most commonly isolated clinical pathogen and was found in 43 (19.9%) samples. In 66 (94.3%) of the 70 staff members for whom bacteria were detected on their MPs, the same bacteria were detected in nares or hand. Among 31 medical staff who were carriers of SA in the anterior nares or dominant hand, 8 (25.8%) were found to have SA on their MPs, and genotyping confirmed the same SA strain in 7 (87.5%) of them. Conclusion: A high rate of bacterial nasal colonization and MPs contamination were found among the OR medical staff. An MP may be a reservoir for pathogen contamination in the OR. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is one of the major pathogens causing bovine intramammary infections (IMIs) and mastitis. Mastitis is the primary cause for the use of antibiotics in dairy farms but therapeutic failure is often observed. One of the reasons for the lack of effectiveness of antibiotic therapy despite the observed susceptibility of bacterial isolates in vitro are bacterial biofilms. In this study, we used chitosan of well-defined molecular weight (0.4–0.6, 1.3, 2.6 and 4.0 kDa) and investigated their antibiofilm and antibacterial activities in in vitro and in vivo models related to S. aureus IMIs. A chitosan of at least 6 units of glucosamine was necessary for maximum antibacterial activity. The 2.6 and 4.0 kDa forms were able to prevent biofilm production by the biofilm hyperproducer strain S. aureus 2117 and a bovine MRSA (methicillin-resistant S. aureus). The intramammary administration of the 2.6 kDa chitosan showed no adverse effects in mice or in cows, as opposed to the slight inflammatory effect observed in mammary glands with the 4.0 kDa derivative. The 2.6 kDa chitosan killed bacteria embedded in pre-established biofilms in a dose-dependent manner with a >3 log10 reduction in CFU at 4 mg/ml. Also, the 2.6 kDa chitosan could prevent the persistence of the internalized MRSA into the mammary epithelial cell line MAC-T. An in vitro checkerboard assay showed that the 2.6 kDa chitosan produced a synergy with the macrolide class of antibiotics (e.g., tilmicosin) and reduced the MIC of both molecules by 2–8 times. Finally, the intramammary administration of the 2.6 kDa chitosan alone (P<0.01) or in combination with tilmicosin (P<0.0001) reduced the colonization of mammary glands in a murine IMI model. Our results suggest that the use of chitosan alone or in combination with a low dose of a macrolide could help reduce antibiotic use in dairy farms. [ABSTRACT FROM AUTHOR]

The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), including strains resistant to current antibiotics, has contributed to an increase in the number of skin infections reported in humans in recent years. New therapeutic options are needed to counter this public health challenge. The aim of the present study was to examine the potential of thiazole compounds synthesized by our research group to be used topically to treat MRSA skin and wound infections. The broth microdilution method confirmed that the lead thiazole compound and four analogues are capable of inhibiting MRSA growth at concentrations as low as 1.3 μg/mL. Additionally, three compounds exhibited a synergistic relationship when combined with the topical antibiotic mupirocin against MRSA in vitro via the checkerboard assay. Thus the thiazole compounds have potential to be used alone or in combination with mupirocin against MRSA. When tested against human keratinocytes, four derivatives of the lead compound demonstrated an improved toxicity profile (were found to be non-toxic up to a concentration of 20 μg/mL). Utilizing a murine skin infection model, we confirmed that the lead compound and three analogues exhibited potent antimicrobial activity in vivo, with similar capability as the antibiotic mupirocin, as they reduced the burden of MRSA present in skin wounds by more than 90%. Taken altogether, the present study provides important evidence that these thiazole compounds warrant further investigation for development as novel topical antimicrobials to treat MRSA skin infections. [ABSTRACT FROM AUTHOR]

Staphylococcus pseudintermedius is a commensal organism of companion animals that is a significant source of opportunistic infections in dogs. With the emergence of clinical isolates of S. pseudintermedius (chiefly methicillin-resistant S. pseudintermedius (MRSP)) exhibiting increased resistance to nearly all antibiotic classes, new antimicrobials and therapeutic strategies are urgently needed. Thiazole compounds have been previously shown to possess potent antibacterial activity against multidrug-resistant strains of Staphylococcus aureus of human and animal concern. Given the genetic similarity between S. aureus and S. pseudintermedius, this study explores the potential use of thiazole compounds as novel antibacterial agents against methicillin-sensitive S. pseudintermedius (MSSP) and MRSP. A broth microdilution assay confirmed these compounds exhibit potent bactericidal activity (at sub-microgram/mL concentrations) against both MSSA and MRSP clinical isolates while the MTS assay confirmed three compounds (at 10 μg/mL) were not toxic to mammalian cells. A time-kill assay revealed two derivatives rapidly kill MRSP within two hours. However, this rapid bactericidal activity was not due to disruption of the bacterial cell membrane indicating an alternative mechanism of action for these compounds against MRSP. A multi-step resistance selection analysis revealed compounds 4 and 5 exhibited a modest (two-fold) shift in activity over ten passages. Furthermore, all six compounds (at a subinihibitory concentration) demonstrated the ability to re-sensitize MRSP to oxacillin, indicating these compounds have potential use for extending the therapeutic utility of β-lactam antibiotics against MRSP. Metabolic stability analysis with dog liver microsomes revealed compound 3 exhibited an improved physicochemical profile compared to the lead compound. In addition to this, all six thiazole compounds possessed a long post-antibiotic effect (at least 8 hours) against MRSP. Collectively the present study demonstrates these synthetic thiazole compounds possess potent antibacterial activity against both MSSP and MRSP and warrant further investigation into their use as novel antimicrobial agents. [ABSTRACT FROM AUTHOR]

Background: Most medicinal plants contain a mixture of bioactive compounds, including chemicals that interact with intracellular targets and others that can act as adjuvants to facilitate absorption of polar agents across cellular membranes. However, little is known about synergistic effects between such potential drug candidates and adjuvants. To probe for such effects, we tested the green tea compound epigallocatechin gallate (EGCG) and the membrane permeabilising digitonin on Plasmodium sporozoite motility and viability. Methodology/Principal Findings: Green fluorescent P. berghei sporozoites were imaged using a recently developed visual screening methodology. Motility and viability parameters were automatically analyzed and IC50 values were calculated, and the synergism of drug and adjuvant was assessed by the fractional inhibitory concentration index. Validating our visual screening procedure, we showed that sporozoite motility and liver cell infection is inhibited by EGCG at nontoxic concentrations. Digitonin synergistically increases the cytotoxicity of EGCG on sporozoite survival, but shows an additive effect on sporozoite motility. Conclusions/Significance: We proved the feasibility of performing highly reliable visual screens for compounds against Plasmodium sporozoites. We thereby could show an advantage of administering mixtures of plant metabolites on inhibition of cell motility and survival. Although the effective concentration of both drugs is too high for use in malaria prophylaxis, the demonstration of a synergistic effect between two plant compounds could lead to new avenues in drug discovery. [ABSTRACT FROM AUTHOR]