Longitudinal antimicrobial susceptibility trends of canine Staphylococcus pseudintermedius.

Antimicrobial resistance within Staphylococcus pseudintermedius poses a significant risk for the treatment of canine pyoderma and as a reservoir for resistance and potential zoonoses, but few studies examine long-term temporal trends of resistance. This study assesses the antimicrobial resistance prevalence and minimum inhibitory concentration (MIC) trends in S. pseudintermedius (n=1804) isolated from canine skin samples at the Cornell University Animal Health Diagnostic Center (AHDC) between 2007 and 2020. Not susceptible (NS) prevalence, Cochran-Armitage tests, logrank tests, MIC50 and MIC90 quantiles, and survival analysis models were used to evaluate resistance prevalence and temporal trends to 23 antimicrobials. We use splines as predictors in accelerated failure time (AFT) models to model non-linear temporal trends in MICs. Multidrug resistance was common among isolates (47%), and isolates had moderate to high NS prevalence to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, the macrolides/lincosamides, the tetracyclines, and trimethoprim-sulfamethoxazole. However, low levels of NS to amikacin, rifampin, and vancomycin were observed. Around one third of isolates (38%) were found to be methicillin resistant S. pseudintermedius (MRSP), and these isolates had a higher prevalence of NS to all tested antimicrobials than methicillin susceptible isolates. Amongst the MRSP isolates, one phenotypically vancomycin resistant isolate (MIC >16 µg/mL) was identified, but genomic sequence data was unavailable. AFT models showed increasing MICs across time to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, and the macrolides/lincosamides, and decreasing temporal resistance (decreasing MICs) to doxycycline was observed amongst isolates. Notably, ATF modeling showed changes in MIC distributions that were not identified using Cochran-Armitage tests on prevalence, MIC quantiles, and logrank tests. Increasing resistance amongst these S. pseudintermedius isolates highlights the need for rational, empirical prescribing practices and increased antimicrobial resistance (AMR) surveillance to maintain the efficacy of current therapeutic agents. AFT models with non-linear predictors may be a useful, breakpoint-independent, surveillance tool alongside other modeling methods and antibiograms.

Source tracking of extensively drug resistant Salmonella Typhi in food and raw vegetables using molecular approaches.

INTRODUCTION: Extensively drug resistant (XDR) strains of the Salmonella lineages have been reported to spread from Africa to South Asia. XDR strains are resistant to fluoroquinolones, chloramphenicol, co-trimoxazole, and ampicillin, resulting in treatment failure. The objectives of this study included the investigation of transmission of S. Typhi lineages and the identification of the potentially contaminated sources of the XDR typhoid outbreak from different urban areas by using molecular techniques. METHODOLOGY: Environmental samples, including food samples, were collected from different towns and the susceptibility of each isolate to the antimicrobial agents was examined. Molecular identification of different Salmonella lineages including S. Typhi, S. Paratyphi A, H58, and XDR was carried out through multiplex PCR. RESULTS AND CONCLUSIONS: A total of 328 environmental samples including raw vegetables, water, and bakery items were collected. More than half of the tested samples (64%) found harboring Salmonella spp. The Salmonella was confirmed through PCR amplification of species-specific markers that showed the presence of S. Typhi (40%), S. Paratyphi A (8%), H58 (7%), and XDR S. Typhi (6%). Raw vegetables had the highest number of Salmonella spp., indicating consumption of raw vegetables as a possible source of salmonellosis. XDR status was also affirmed through phenotypic antimicrobial susceptibility testing.

Corneal stromal ulcerations in a referral population of dogs and cats in the Netherlands (2012-2019): Bacterial isolates and antibiotic resistance.

OBJECTIVE: To evaluate bacterial isolates from corneal stromal ulcerations in dogs and cats in the Netherlands, review their antibiotic susceptibility, determine whether recent topical treatment affected bacterial culture results, and investigate whether (multi-drug) resistance patterns changed over time. ANIMALS STUDIED: Client-owned dogs and cats were diagnosed with corneal stromal ulceration at the Utrecht University Clinic for Companion Animals between 2012 and 2019. PROCEDURES: Retrospective analysis. RESULTS: In total, 163 samples were collected from 122 dogs (130 samples) and 33 cats. Positive cultures were obtained from 76 canine and 13 feline samples (59% and 39%, respectively) and included Staphylococcus (42 in dogs, 8 in cats), Streptococcus (22 in dogs, 2 in cats), and Pseudomonas (9 in dogs, 1 in cats) species. Significantly fewer positive cultures were found in dogs and cats previously treated with topical antibiotics (χ2  = 6.52, p = .011 and χ2  = 4.27, p = .039, respectively). Bacterial resistance to chloramphenicol was more common in dogs previously treated with chloramphenicol (χ2  = 5.24, p = .022). The incidence of acquired antibiotic resistance did not increase significantly over time. In dogs, the incidence of multi-drug-resistant isolates increased significantly between 2012-2015 and 2016-2019 (9.4% vs. 38.6%, p = .0032). CONCLUSIONS: Staphylococcus, Streptococcus, and Pseudomonas species were the most common bacteria associated with canine and feline corneal stromal ulcerations. Previous treatment with antibiotics affected bacterial culture results and antibiotic sensitivity. Although the overall incidence of acquired antibiotic resistance did not change over time, the incidence of multi-drug-resistant isolates in dogs increased over an 8-year period.

[Efficacy and safety of topical combination therapy in patients with acute otitis externa].

AIM: To study the structure of the microbial landscape in patients with acute otitis externa, as well as to evaluate the efficacy and safety of the combined drug chloramphenicol/clotrimazole/beclomethasone/lidocaine (Candibiotic) as an empirical therapy of this disease. MATERIALS AND METHODS: In this retrospective study of real clinical practice, outpatient records of 963 patients who applied to the KDO of the Sverzhevsky Research Clinical Institute of Otorhinolaryngology with symptoms of otitis externa in the period from 2017 to 2022 were selected. Additional analysis was carried out on the clinical records of patients who received the combined drug Candibiotic. The endpoints of this analysis included data on the clinical and microbiological efficacy of therapy, as well as safety information. RESULTS: According to microbiological testing, 60.6% of microorganisms belonged to bacterial flora, 26% were bacterial-fungal associations, 11.6% were monofungal flora, in 1.8% of cases there was no growth of microorganisms. The most frequently isolated microorganisms were: Pseudomonas spp (n=291; 29.16%), Staphylococcus spp. (n=214; 21.4%), Candida spp. (n=194; 19.4%), Aspergillus spp. (n=133; 13.3%). Most of the patients (71.0%) received Candibiotic. In 69.7% of patients, the resolution of the clinical symptoms of otitis externa occurred within 7 days of therapy with Candibiotic. Complete eradication of microorganisms occurred in 87% of cases. Adverse events were recorded only in 3 (0.04%) cases. CONCLUSION: The study demonstrated an extremely high level of clinical efficacy and safety of therapy in patients with acute external infectious otitis who received the Candibiotic, which can be used as an initial empirical therapy in patients with otitis externa.

A retrospective study on antibacterial treatments for koalas infected with Chlamydia pecorum.

Chlamydiosis remains the leading infectious disease and is one of the key factors responsible for the dramatic reduction of koala populations in South-East Queensland (SEQ) and New South Wales (NSW) regions of Australia. Possible infection outcomes include blindness, infertility, painful cystitis, and death if left untreated. Studies have reported the treatment efficacy of chloramphenicol and doxycycline, which are the two most commonly administered treatments in diseased koalas, in clinical settings. However, none have directly compared the treatment efficacy of these antibacterials on koala survival. A retrospective study was essential to identify any relationships between the demographical information, and the animals' responses to the current treatment regimens. Associations were explored between six explanatory (sex; maturity; location; clinical signs, treatment; treatment duration) and two outcome variables (survival; post-treatment PCR). Results showed that female koalas had a statistical trend of lower odds of surviving when compared to males (OR = 0.36, p = 0.05). Koalas treated with chloramphenicol for ≥ 28 days had greater odds of surviving than when treated for < 28 days (OR = 8.8, p = 0.02), and those koalas administered doxycycline had greater odds of testing PCR negative when compared to chloramphenicol treatments (OR = 5.45, p = 0.008). There was no difference between the antibacterial treatments (chloramphenicol, doxycycline, and mixed/other) and the survival of koalas. Female koalas had greater odds of exhibiting UGT signs only (OR = 4.86, p < 0.001), and also greater odds of having both ocular and UGT clinical signs (OR = 5.29, p < 0.001) when compared to males. Of the koalas, 28.5% initially had no clinical signs but were PCR positive for C. pecorum. This study enables further understanding of the complex nature between chlamydial infection and response to antibacterial treatment.

A meta-analysis on the prevalence of resistance of Staphylococcus aureus to different antibiotics in Nigeria.

BACKGROUND: Rapid emergence of multidrug resistant Staphylococcus aureus has resulted to difficulty in treatment of infections caused by such strains. The aim of this meta-analysis study was to determine the pooled prevalence of resistance of S. aureus to different antibiotics in Nigeria. METHODS: Literature search for studies was done using Google scholar, PubMed, Science direct, and African Journal Online. The prevalence of S. aureus resistance to different antibiotics was evaluated using the meta-analysis proportion command in MedCalc software version 20.0 adopting a rand effect model. I2 statistic and Egger test in MedCalc was used to evaluate the heterogeneity and the presence of publication bias among studies respectively. RESULTS: A total of 40, 682 studies were retrieved through the database search of which 98 studies met the study inclusion criteria. Prevalence of resistance of S. aureus to different antibiotics ranges from 13 to 82%. Results showed a very high degree of resistance to penicillin G (82% [95% confidence interval (CI) 61%, 0.96%]), cloxacillin (77% [95% CI 64%, 88%]), amoxacillin (74% [95% CI 66%, 81%]), cefuroxime (69% [95% CI 51%, 85%]), ampicillin (68% [95% CI 53%, 81%]). Moderately resistance to erythromycin (47% [95% CI 40%, 53%]), chloramphenicol (47% [95% CI 37%, 56%]), methicillin (46% [95% CI 37%, 56%]), ofloxacin (24% [95% CI 18%, 31%]) and rifampicin 24% [95% CI 6%, 48%]). Low resistance was observed in vancomycin 13% (95% CI 7%, 21%). For each individual meta-analysis, high heterogeneity was observed with I2 range (79.36-98.60%) at p-values ≤ 0.01). Egger's tests for regression intercept in funnel plots indicated no evidence of publication bias. CONCLUSION: This meta-analysis study established that S. aureus in Nigeria has developed resistance to commonly used antibiotics such as the beta-lactam class antibiotics, sulphonamides, tetracyclines, chloramphenicol, and vancomycin. Hence it is imperative to develop programs to promote rational use of antimicrobial agents, infection prevention and control to reduce the incidence of antimicrobial resistance.

Frequency and Antibiotics Sensitivity Pattern of Culture-Positive Salmonella Typhi in Children.

OBJECTIVE: To calculate the frequency of positive blood culture in clinically diagnosed cases of enteric fever and antibiotic sensitivity patterns in culture-positive cases of S.typhi Study Design: Observational Study. Place and Duration of the Study: Department of Paediatrics Medicine, Services Hospital Lahore, from November 15th 2020 to May 15th 2021. METHODOLOGY: A total of 246 patients, fulfilling the definition of a suspected case of enteric fever were enrolled. Blood cultures were drawn on the spot. Antimicrobial sensitivity for 8 antimicrobial agents-Ampicillin, amoxicillin, chloramphenicol, cefixime, ceftriaxone, cefotaxime, ciprofloxacin, meropenem, and Azithromycin, were performed. A p-value of <0.05 was considered statistically significant. RESULTS: Blood cultures were positive in 62 (25.2%), patients out of which 34 (54.9%) were females and 28 (45.1%) were males, of which, 58 were S. typhi and 4 were S. Paratyphi A or B. Cefixime was sensitive in 27.4% of patients and intermediate sensitivity was found in 3.2% of cases and 69.4% of cases were resistant, ceftriaxone was sensitive in 38.7% of cases and Azithromycin was sensitive in 96.7% of cases, whereas meropenem showed 100% sensitivity. Chloramphenicol and Ciprofloxacin were resistant in 80.6% and 27.3% of the cases respectively. Among isolates, 32.3% (20) were categorised as sensitive enteric fever; 64.5% (40) as MDR, and 3.2% (2) as XDR enteric fever. CONCLUSION: MDR and XDR enteric fever are a major concern. For such cases, Azithromycin remains the best oral antibiotic with a sensitivity of up to 96.7%. Meropenem was sensitive in 100% of cases and was the only antibiotic with no documented resistance in this study. KEY WORDS: Enteric fever, Salmonella, Antibiotic sensitivity, Blood culture, MDR, XDR, Azithromycin, Meropenem.

Novel use of oral chloramphenicol for treatment-resistant Mycoplasma genitalium.

We describe the novel use of oral chloramphenicol for treatment-resistant Mycoplasma genitalium (M. genitalium) infection in a 20-year-old heterosexual cisgender male presenting with recurrent symptomatic non-gonococcal urethritis. M. genitalium urethritis is an increasingly common clinical conundrum in sexual health clinics and in cases of second-line treatment failure (such as moxifloxacin), UK and international guidelines struggle to make recommendations for third-line treatments. As shown in our case, the evidence base for third-line treatments is lacking, with poor success rates, and may be poorly tolerated. Here we demonstrate the novel use of a well-tolerated oral antimicrobial, chloramphenicol, resulting in rapid microbiological and clinical cure in treatment-resistant M. genitalium urethritis.

Plague Meningitis: A Systematic Review of Clinical Course, Antimicrobial Treatment, and Outcomes.

Plague meningitis is a serious and often fatal manifestation of Yersinia pestis infection. In the aftermath of a bioweapon attack with Y pestis, this typically rare manifestation may develop in a substantial number of patients, particularly if treatment delays occur. Risk factors, clinical evolution, and optimal treatment strategies for plague meningitis are not well understood. We searched PubMed Central and other databases for reports of plague meningitis in any language. Articles containing descriptions of patients with plague meningitis and their treatment and outcomes were included. Among 1,496 articles identified in our search, 56 articles describing 84 cases from 1898 to 2015 met inclusion criteria. The median age of patients was 16 years (range 6 weeks to 64 years); 68% were male. Most patients (n = 50, 60%) developed meningitis following primary bubonic plague. Common signs and symptoms included fever (n = 56, 66%), nuchal rigidity (n = 38, 45%), and headache (n = 33, 36%); 29% (n = 24) of patients had focal neurologic deficits such as cranial nerve abnormalities. Almost all (n = 23, 96%) of the 24 patients who did not receive antimicrobials died, and 42% (n = 25) of the 59 patients treated with antimicrobials died. The case fatality rate of patients grouped by antimicrobial received was 50% (1 out of 2) for fluoroquinolones, 19% (4 out of 21) for aminoglycosides, 14% (2 out of 14) for sulfonamides, 11% (2 out of 18) for chloramphenicol, and 0% (0 out of 13) for tetracyclines. Plague meningitis most often occurs as a complication of bubonic plague and can cause focal neurologic deficits. Survival is more likely in patients who receive antimicrobials; tetracyclines, aminoglycosides, and chloramphenicol had the lowest associated case fatality rates.

Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins.

BACKGROUND: Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. OBJECTIVES: To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. MAIN RESULTS: We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low-certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low-certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low-certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low-certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low-certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low-certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of -0.52 days, 95% CI -0.91 to -0.12; 3 trials, 196 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low-certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low-certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low-certainty evidence) and time to defervescence (MD 2.73 days, 95% CI -0.37 to 5.84; 3 trials, 285 participants; very low-certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low-certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Based on very low- to low-certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones.  We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.

ANALYSIS OF ANTIBIOTIC RESISTANCE OF CONDITIONALLY PATHOGENIC OROPHARYNGEAL MICROFLORA IN CHILDREN AFTER VIRAL RESPIRATORY INFECTIONS.

The purpose of the was to compare the antibiotic resistance of the oropharyngeal normoflora in children with frequent Viral respiratory infections (VRIs). Investigated were 33 children in 2016 and 33 children in 2021 who were treated in the Infectious Diseases Department of the Ternopil Regional (Ukraine) Children's Clinical Hospital. The obtained material from the oropharynx from the examined contingent was studied by a generally accepted microbiological method. Determination of antibiotic susceptibility of the selected strains was performed by the method of standard disks. Among surveyed children in 2016 year were 20 (60.60%) carriers of staphylococci, with 12 children of them actually S. aureus. In 2021 were different types of streptococci were isolated from almost half (15 patient) of the subjects: α-hemolytic - 51.60%, ß-hemolytic - 45.50% of patients with VRIs and S. aureus. -48.5 %. Analysis of antibiotic susceptibility of staphylococci and streptococci revealed a significant reduction in the number of susceptible staphylococcal strains to cephalosporin and penicillin, moderate - against aminoglycosides and chloramphenicol. Almost all of the studied microorganisms were insensitive to erythromycin. Over the past 5 years, the number of staphylococcal strains sensitive to ceftriaxone decreased by more than 50% (65.0% in 2016 and 14.3% in 2021), to chloramphenicol by 28.7%, ampicillin by 14.4%. The number of streptococci sensitive to all groups of antibiotics decreased by 3-4% 2021 compared to 2016, only to ampicillin the number of sensitive strains decreased by 16%.

Analysis of the Antimicrobial and Anti-Biofilm Activity of Natural Compounds and Their Analogues against Staphylococcus aureus Isolates.

(1) Background: Staphylococcus aureus (S. aureus) is one of the most frequent causes of biofilm-associated infections. With the emergence of antibiotic-resistant, especially methicillin-resistant S. aureus (MRSA), there is an urgent need to discover novel inhibitory compounds against this clinically important pathogen. In this study, we evaluated the antimicrobial and anti-biofilm activity of 11 compounds, including phenyl propenes and phenolic aldehydes, eugenol, ferulic acid, sinapic acid, salicylaldehyde, vanillin, cinnamoyl acid, and aldehydes, against drug-resistant S. aureus isolates. (2) Methods: Thirty-two clinical S. aureus isolates were obtained from Alkhidmat Diagnostic Center and Blood Bank, Karachi, Pakistan, and screened for biofilm-forming potential, and susceptibility/resistance against ciprofloxacin, chloramphenicol, ampicillin, amikacin, cephalothin, clindamycin, streptomycin, and gentamicin using the Kirby-Bauer disk diffusion method. Subsequently, 5 representative clinical isolates were selected and used to test the antimicrobial and anti-biofilm potential of 11 compounds using both qualitative and quantitative assays, followed by qPCR analysis to examine the differences in the expression levels of biofilm-forming genes (ica-A, fnb-B, clf-A and cna) in treated (with natural compounds and their derivatives) and untreated isolates. (3) Results: All isolates were found to be multi-drug resistant and dominant biofilm formers. The individual Minimum Inhibitory Concentration (MIC) of natural compounds and their analogues ranged from 0.75−160 mg/mL. Furthermore, the compounds, Salicylaldehyde (SALI), Vanillin (VAN), α-methyl-trans-cinnamaldehyde (A-MT), and trans-4-nitrocinnamic acid (T4N) exhibited significant (15−92%) biofilm inhibition/reduction percentage capacity at the concentration of 1−10 mg/mL. Gene expression analysis showed that salicylaldehyde, α-methyl-trans-cinnamaldehyde, and α-bromo-trans-cinnamaldehyde resulted in a significant (p < 0.05) downregulation of the expression of ica-A, clf-A, and fnb-A genes compared to the untreated resistant isolate. (4) Conclusions: The natural compounds and their analogues used in this study exhibited significant antimicrobial and anti-biofilm activity against S. aureus. Biofilms persist as the main concern in clinical settings. These compounds may serve as potential candidate drug molecules against biofilm forming S. aureus.

Bacterial isolates from diabetic foot ulcers and their antimicrobial resistance profile from selected hospitals in Addis Ababa, Ethiopia.

Introduction: Infected diabetic foot ulcer (IDFU) is a worldwide problem associated with diabetes mellitus. It could lead from soft tissue infection to bone infection and is a leading cause of lower limb amputation. Gram-negative and Gram-positive bacteria, including anaerobic bacteria and fungi, are considered potential causes of infection. The early diagnosis of DFU infection and appropriate treatment based on the identification of the pathogens and their antimicrobial susceptibility pattern is important for good prognosis. Therefore, the purpose of this study was to isolate the bacteria that infect foot ulcers in selected Hospitals and determine their antimicrobial resistance profile. Method: An institutional-based multicenter, cross-sectional study was conducted in selected Hospitals in Addis Ababa, Ethiopia, from November 2020 to May 2021. A sterile swab was used to collect samples from the foot ulcer and a sterile needle to collect pus. Isolates were identified by culture, Gram-staining, and a series of biochemical tests. For each bacterial species identified, the antibiotic profiling was determined by the Kirby-Bauer disk diffusion method. Results: one hundred and twenty-seven pathogenic bacteria were isolated from samples taken from 130 patients with a diabetic foot ulcer. Sixty-eight percent had growth of multiple microorganisms. Two-thirds (66.7%) of the isolates were gram-negative bacteria. The predominant bacterial species were S. aureus 25.19% (32/127), Pseudomonas species 18.89% (24/127), and Escherichia coli 16.53% (21/127). Overall, 92.9% (118/127) of the isolates were identified as multi-drug resistant. Gram-positive isolates were susceptible to chloramphenicol, clindamycin, and amikacin. Gram-negative isolates were also sensitive to chloramphenicol, aztreonam, and amikacin. Conclusion: The majority of bacteria isolated from patients presenting with Diabetic foot ulcer infections were found to be multi-drug resistant in the study sites of the current study. The results demonstrate the importance of timely identification of infection of diabetic foot ulcers, proper sample collection for identification of the pathogens and for determining their antibiotic susceptibility pattern before initiating antimicrobial treatment.

Short Chain Fatty Acids (SCFAs) Are the Potential Immunomodulatory Metabolites in Controlling Staphylococcus aureus-Mediated Mastitis.

Mastitis is an emerging health concern in animals. An increased incidence of mastitis in dairy cows has been reported in the last few years across the world. It is estimated that up to 20% of cows are suffering from mastitis, causing incompetency in the mucosal immunity and resulting in excessive global economic losses in the dairy industry. Staphylococcus aureus (S. aureus) has been reported as the most common bacterial pathogen of mastitis at clinical and sub-clinical levels. Antibiotics, including penicillin, macrolides, lincomycin, cephalosporins, tetracyclines, chloramphenicol, and methicillin, were used to cure S. aureus-induced mastitis. However, S. aureus is resistant to most antibiotics, and methicillin-resistant S. aureus (MRSA) especially has emerged as a critical health concern. MRSA impairs immune homeostasis leaving the host more susceptible to other infections. Thus, exploring an alternative to antibiotics has become an immediate requirement of the current decade. Short chain fatty acids (SCFAs) are the potent bioactive metabolites produced by host gut microbiota through fermentation and play a crucial role in host/pathogen interaction and could be applied as a potential therapeutic agent against mastitis. The purpose of this review is to summarize the potential mechanism by which SCFAs alleviate mastitis, providing the theoretical reference for the usage of SCFAs in preventing or curing mastitis.

Clinical outcomes of doxycycline, azithromycin and chloramphenicol for the treatment of patients with severe scrub typhus.

BACKGROUND: Previous studies have evaluated treatment efficacy of various antibiotics for patients with mild-to-moderate scrub typhus (ST). However, the efficacy of different antibiotics for treating severe ST remains uncertain. METHODS: A retrospective study of patients with severe ST was undertaken in China. The treatment efficacy rates of doxycycline, azithromycin and chloramphenicol were compared, using treatment failure and time to defervescence as primary outcomes. RESULTS: In total, 876 patients with severe ST who initially received doxycycline, azithromycin or chloramphenicol were recruited. The treatment failure rate did not differ significantly between patients receiving doxycycline and patients receiving azithromycin (6.0% vs 11.4%; P=0.109). However, a higher treatment failure rate was observed for chloramphenicol compared with doxycycline (14.6% vs 6.0%; P=0.004). No significant difference in time to defervescence was observed between patients receiving doxycycline, azithromycin or chloramphenicol. Further subgroup analysis revealed a higher risk of treatment failure for chloramphenicol compared with doxycycline in patients with acute kidney injury, pneumonia and shock; and a higher risk of treatment failure for azithromycin compared with doxycycline in patients with meningitis. Significant correlation was found between azithromycin resistance and meningitis (P=0.009), and between chloramphenicol resistance and acute respiratory distress syndrome (ARDS) (P<0.001) using Cramer's V correlation coefficient. Multi-variate Cox regression analysis revealed significant associations between time to defervescence and presence of ARDS, shock, myocarditis, meningitis and acute kidney injury. CONCLUSION: Azithromycin and doxycycline were found to have significant therapeutic effects in patients with severe ST. In contast, chloramphenicol was less efficacious for the treatment of these patients.

Evaluation of the Therapeutic Effect of Antibiotics on Scrub Typhus: A Systematic Review and Network Meta-Analysis.

Background: To explore the efficacy and safety of drugs in patients with scrub typhus. Methods: For this systematic review and network meta-analysis, we searched PubMed, Embase, Web of Science, Cochrane Central Register of Clinical Trials, China National Knowledge Infrastructure (CNKI), and Wanfang data (WF) up to December 2021. All randomized controlled trials (RCTs) of antibiotics used to treat scrub typhus were included without language or date restrictions. The overall effectiveness was evaluated from 4 perspectives: cure rate (CR), defervescence time (DT), gastrointestinal symptoms-adverse events (GS-AD), and abnormal blood count-adverse events (ABC-AD). The quality of evidence was evaluated using the Cochrane Risk of Bias tool and GRADE system. Results: Sixteen studies involving 1,582 patients were included to evaluate 7 drugs, namely, azithromycin, doxycycline, chloramphenicol, tetracycline, rifampin, moxifloxacin, and telithromycin. In this network meta-analysis, rifampicin (82%) and chloramphenicol (65%) were more effective in terms of CR, and moxifloxacin (3%) from the quinolone family was the worst. Azithromycin caused the fewest events in terms of ABC-AD. No differences were found in this network meta-analysis (NMA) in terms of DT and GS-AD. Conclusions: Rifampicin was associated with the highest CR benefit and the lowest risk of DT when used to treat patients with scrub typhus, except in areas where tuberculosis (TB) was endemic. Azithromycin was found to be better in CR and was associated with a lower probability of GS-AD and ABC-AD; therefore, it may be considered to treat pregnant women and children. Moxifloxacin had a much lower CR than other drugs and is, therefore, not recommended for the management of scrub typhus. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021287837.

Antibiotic prophylaxis for corneal abrasion.

BACKGROUND: Corneal abrasion is a common disorder frequently faced by ophthalmologists, emergency physicians, and primary care physicians. Ocular antibiotics are one of the management options for corneal abrasion. A comprehensive summary and synthesis of the evidence on antibiotic prophylaxis in traumatic corneal abrasion is thus far unavailable, therefore we conducted this review to evaluate the current evidence regarding this important issue. OBJECTIVES: To assess the safety and efficacy of topical antibiotic prophylaxis following corneal abrasion. Our objectives were 1) to investigate the incidence of infection with antibiotics versus placebo or alternative antibiotics in people with corneal abrasion; and 2) to investigate time to clinical cure, defined as complete healing (re-epithelialization) of the epithelium, with antibiotics versus placebo or alternative antibiotics in people with corneal abrasion. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4), Ovid MEDLINE, Embase.com, PubMed, the Latin American and Caribbean Health Sciences Literature database (LILACS), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 25 April 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing antibiotic with another antibiotic or placebo in children and adults with corneal abrasion due to any cause. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for the prespecified outcomes using the GRADE classification. MAIN RESULTS: Our search of the electronic databases yielded 8661 records. We screened 7690 titles and abstracts after removal of duplicates. We retrieved 32 full-text reports for further review. We included two studies that randomized a total of 527 eyes of 527 participants in the review. One study was conducted in Denmark, and one was conducted in India. The two studies did not examine most of our prespecified primary and secondary outcomes. The first study was a parallel-group RCT comparing chloramphenicol ocular ointment with fusidic acid ocular gels (frequency was not clearly reported). This study enrolled 153 participants older than 5 years of age with corneal abrasion in Denmark with a one-day follow-up duration. No participants had secondary infection in the fusidic acid group, whereas three (4.1%) participants in the chloramphenicol group had a slight reaction (risk ratio [RR] 0.15, 95% confidence interval [CI] 0.01 to 2.79; 144 participants; very low certainty evidence). Thirty-one (44.3%) participants in the fusidic acid arm and 34 (46.6%) participants in the chloramphenicol arm were cured (defined as the area of abrasion zero and no infection) at day 1 (RR 0.94, 95% CI 0.65 to 1.34; 144 participants; very low certainty evidence). Without providing specific data, the study reported that the degree of pain was not affected by the interventions received. The most common adverse events reported were itching and discomfort of the eye, which occurred in approximately one-third of participants in each group (low certainty evidence). A second multicenter, two-arm RCT conducted in India enrolled 374 participants older than 5 years of age with corneal abrasion who presented within 48 hours after injury. This study investigated the effect of a three-day course of either ocular ointment combinations of chloramphenicol-clotrimazole or chloramphenicol-placebo (all three times daily). At day 3, 169 (100%) participants in the chloramphenicol-clotrimazole arm and 203 (99%) out of 205 participants in the chloramphenicol-placebo arm were cured without any complication, defined as complete epithelialization of the cornea without evidence of infection (RR 1.01, 95% CI 0.99 to 1.03; 374 participants; very low certainty evidence). Four participants assigned to the chloramphenicol-placebo arm experienced mild adverse events: two participants (1%) had mild chemosis and irritation, and two (1%) had small single sterile corneal infiltrates (low certainty evidence). AUTHORS' CONCLUSIONS: Given the low to very low certainty of the available evidence, any beneficial effects of antibiotic prophylaxis in preventing ocular infection or accelerating epithelial healing following a corneal abrasion remain unclear. Moreover, the current evidence is insufficient to support any antibiotic regimen being superior to another. There is a need for a well-designed RCT assessing the efficacy and safety of ocular antibiotics in the treatment of corneal abrasion with a particular focus on high-risk populations and formulation of interventions.

The perspective of antibiotic therapeutic challenges of brucellosis in the Middle East and North African countries: Current situation and therapeutic management.

Brucellosis is among the most prevalent zoonotic infections in Middle Eastern and North African (MENA) countries, critically impacting human and animal health. A comprehensive review of studies on antibiotic susceptibility and therapeutic regimes for brucellosis in ruminants and humans in the MENA region was conducted to evaluate the current therapeutic management in this region. Different scientific databases were searched for peer-reviewed original English articles published from January 1989 to February 2021. Reports from research organizations and health authorities have been taken into consideration. Brucella melitensis and Brucella abortus have been reported from the majority of MENA countries, suggesting a massive prevalence particularly of B. melitensis across these countries. Several sporadic cases of brucellosis relapse, therapeutic failure, and antibiotic resistance of animal and human isolates have been reported from the MENA region. However, several studies proved that brucellae are still in-vitro susceptible to the majority of antibiotic compounds and combinations in current recommended World Health Organization (WHO) treatment regimens, for example, levofloxacin, tetracyclines, doxycycline, streptomycin, ciprofloxacin, chloramphenicol, gentamicin, tigecycline, and trimethoprim/sulfamethoxazole. The current review presents an overview on resistance development of brucellae and highlights the current knowledge on effective antibiotics regimens for treating human brucellosis.

The burden of methicillin-resistant Staphylococcus aureus in the delivery of eye care.

BACKGROUND: To describe the clinical presentation, burden and antimicrobial resistance of Methicillin-Resistant Staphylococcus aureus (MRSA) eye infections and to recommend a streamlined protocol for the management of ocular MRSA colonisation detected by pre-operative screening. METHODS: A retrospective review of all ocular samples which resulted in the isolation of MRSA between 1st of January 2013 and 31st of December 2019 at the Royal Victoria Eye and Ear Hospital. RESULTS: A total of 185 samples taken from the ocular surface were MRSA positive. The majority were MRSA colonisation of the ocular surface obtained as part of an MRSA screen (139/6955 patients screened; 2%). Forty-six represented MRSA infections (46/7904 eye samples; 0.58%), most occurring in older patients the majority of whom had known local or systemic risk factors for colonisation. The most common presentation was conjunctivitis (n = 24), followed by pre-septal cellulitis (n = 9). MRSA infections with the poorest clinical outcomes and the longest inpatient stay, were keratitis (n = 6) and post-operative endophthalmitis (n = 2). Our study demonstrated over 60% resistance to azithromycin, fusidic acid and ciprofloxacin, although resistance to chloramphenicol was uncommon. CONCLUSION: This study demonstrates that MRSA infections of the eye most commonly manifest as a mild infection, typically conjunctivitis, and are generally non-sight threatening. The majority of presentations occur in the context of known MRSA risk factors and in an older populous. Resistance to chloramphenicol is rare, thus it remains an excellent first line treatment. Its use to eradicate MRSA from the ocular surface is proposed to streamline the delivery of surgical eye care.