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.

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.

[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.

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.

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 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.

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%.

Prevalence of Salmonella enterica serovar Typhi infection, its associated factors and antimicrobial susceptibility patterns among febrile patients at Adare general hospital, Hawassa, southern Ethiopia.

BACKGROUND: Salmonellas enterica serovar Typhi (S.typhi) causes typhoid fever and is a global health problem, especially in developing countries like Ethiopia. But there is a little information about prevalence and factors association with S.typhi and its antimicrobial susceptibility pattern in Ethiopia especially in the study area. The aim of this study was to determine the prevalence of S.typhi infection, its associated factors and antimicrobial susceptibility pattern among patient with a febrile illness at Adare General Hospital, Hawassa, Southern Ethiopia. METHODS: Hospital based cross sectional study was conducted among 422 febrile patients from May 23, 2018 to October 20, 2018. A 5 ml venous blood was collected from each febrile patient. Culture and biochemical test were performed for each isolate. Antimicrobial susceptibility testing was performed for each isolate using modified Kirby-Bauer disk diffusion techniques. RESULT: In this study, the prevalence of S.typhi among febrile illness patients at Adare General Hospital was 1.6% [95% confidence interval (CI): 0.5-2.9]. The age of the study subjects were ranged from 15 to 65 years (mean age 32 years). It was observed that participants who came from rural area had 8 times (AOR 8.27: 95% CI: 1.33, 51.55) more likely to had S. typhi infection when compared with urban dwellers. The microbial susceptibility testing revealed that all six of S.typhi isolates showed sensitive to Ceftriaxone and all 6 isolates showed resistant to nalidixic acid and Cefotaxime and 5(83.3%) susceptible to Chloramphenicol and Ciprofloxaciline. Multidrug resistance (resistance to three or more antibiotics) was observed among most of the isolates. CONCLUSION: S. typhi bacteraemia is an uncommon but important cause of febrile illness in our study population. Ceftriaxone therapy is a suitable empirical antibiotic for those that are unwell and suspected of having this illness. Further surveillance is required to monitor possible hanging antibiotic resistant patterns in Ethiopia.

Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial.

BACKGROUND: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%. OBJECTIVE: To investigate prophylactic topical treatment for EGFRI-induced rash. METHODS: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. RESULTS: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. CONCLUSIONS: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.

EFFICACY AND SAFETY OF CHLORAMPHENICOL TREATMENT FOR BATRACHOCHYTRIUM DENDROBATIDIS IN HELLBENDERS (CRYPTOBRANCHUS ALLEGANIENSIS).

Thirteen wild-caught hellbenders (Cryptobranchus alleganiensis) were treated for Batrachochytrium dendrobatidis with continuous chloramphenicol baths at concentrations of 20 mg/L for 14 days and 200 mg/L for 14 days. Clinical signs and deaths continued after treatment with 20 mg/L chloramphenicol but ceased after treatment with 200 mg/L chloramphenicol. No evidence of toxicity was found on hematologic tests, necropsy, or histopathologic examination. Lower infection burdens were detected after treatment with chloramphenicol, but infection rates were unchanged. Chloramphenicol may be useful as a treatment for B. dendrobatidis in hellbenders but did not clear hellbenders of infection.

Determination of Chloramphenicol in Honey Using Salting-Out Assisted Liquid-Liquid Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry and Validation According to 2002/657 European Commission Decision.

Honey is a natural food widely consumed due to its high content in nutrients and bioactive substances. In order to prevent hive infections, xenobiotics such as pesticides and antibiotics are commonly used. Chloramphenicol (CAP) is a broad-spectrum antibiotic used to treat honeybee larvae diseases. However, CAP has toxic and nondose-dependent effects in sensitive subjects; for this reason, its use has been prohibited in food-producing animals, such as the honeybee. In this study, we proposed a rapid, simple, and cheap analytical method, based on salting-out assisted liquid-liquid extraction coupled with UHPLC MS/MS detection for the accurate determination of CAP in honey to be used in routine analyses. The parameters that influence the extraction efficiency have been optimized using an experimental design in order to maximize the recovery of the analyte by reducing the matrix effects. Therefore, the developed method was internally validated according to the 2002/657/EC Decision guidelines and applied to the analysis of 96 honey samples.

Laboratory characterisation of Salmonella enterica serotype Typhi isolates from Zimbabwe, 2009-2017.

BACKGROUND: Typhoid fever remains a major public health problem in Zimbabwe with recurrent outbreaks reported since 2009. To provide guidance on appropriate treatment choice in order to minimise the morbidity and mortality of typhoid fever and prevent large scale outbreaks, we investigated the antimicrobial susceptibility patterns, prevalence of Salmonella enterica serotype Typhi (S. Typhi) H58 haplotype and molecular subtypes of S. Typhi from outbreak strains isolated from 2009 to 2017 in Zimbabwe and compared these to isolates from neighbouring African countries. METHODS: Antimicrobial susceptibility testing was performed on all isolates using the disk diffusion, and E-Test, and results were interpreted using Clinical and Laboratory Standards Institute (CLSI) guidelines (2017). S. Typhi H58 haplotype screening was performed on 161 (58.3%) isolates. Pulsed-field gel electrophoresis (PFGE) was performed on 91 selected isolates across timelines using antibiotic susceptibility results and geographical distribution (2009 to 2016). RESULTS: Between 2009 and 2017, 16,398 suspected cases and 550 confirmed cases of typhoid fever were notified in Zimbabwe. A total of 276 (44.6%) of the culture-confirmed S. Typhi isolates were analysed and 243 isolates (88.0%) were resistant to two or more first line drugs (ciprofloxacin, ampicillin and chloramphenicol) for typhoid. The most common resistance was to ampicillin-chloramphenicol (172 isolates; 62.3%). Increasing ciprofloxacin resistance was observed from 2012 to 2017 (4.2 to 22.0%). Out of 161 screened isolates, 150 (93.2%) were haplotype H58. Twelve PFGE patterns were observed among the 91 isolates analysed, suggesting some diversity exists among strains circulating in Zimbabwe. PFGE analysis of 2013, 2014 and 2016 isolates revealed a common strain with an indistinguishable PFGE pattern (100% similarity) and indistinguishable from PFGE patterns previously identified in strains isolated from South Africa, Zambia and Tanzania. CONCLUSIONS: Resistance to first line antimicrobials used for typhoid fever is emerging in Zimbabwe and the multidrug resistant S. Typhi H58 haplotype is widespread. A predominant PFGE clone circulating in Zimbabwe, South Africa, Zambia and Tanzania, argues for cross-border cooperation in the control of this disease.

Clinical and Radiographic Evaluation of Formocresol and Chloramphenicol, Tetracycline and Zinc Oxide-Eugenol Antibiotic Paste in Primary Teeth Pulpotomies: 24 month follow up.

OBJECTIVE: The purpose of the present study was to evaluate clinically and radiographically the effectiveness of formocresol and the antibiotic paste CTZ (chloramphenicol, tetracycline and zinc oxide-eugenol) in primary teeth pulpotomies, during a 6, 12 and 24 month period. STUDY DESIGN: A total of 80 pulpotomies were performed in 58 patients between three and six years of age. The patients were selected and assigned to two groups: Group I Formocresol (FC, n=40), Group II chloramphenicol-tetracycline-zinc oxide eugenol (CTZ, n=40). The teeth were restored with glass ionomer and pre-formed stainless steel crowns. The treated teeth were evaluated clinically and radiographically at 6, 12 and 24 months. RESULTS: After 24 months of follow up a 100% and 94.3% clinical success was obtained, in the CTZ and formocresol groups respectively (x2= 0.450, p>0.05). The radiographic success was of 97.4% and 94.3% respectively (x2= 0.920, p>0.05). CONCLUSION: The performance of the antibiotic paste CTZ was superior to formocresol. No statistically significant differences were observed between the treatment groups either clinically or radiographically. More randomized clinical trials should be performed before it can be indicated safely.

Otitis in a cat associated with Corynebacterium provencense.

BACKGROUND: The role of corynebacteria in canine and feline otitis has not been investigated in detail; however, members of this genus are increasingly recognized as pathogens of otitis in both human and veterinary medicine. CASE PRESENTATION: Here we report the first case of feline otitis associated with the recently described species Corynebacterium provencense. A seven-month old cat presented with a head tilt and ataxia was diagnosed with peripheral vestibular syndrome associated with an otitis media/interna. This took place 6 weeks after resection of a polyp, having initially shown a full recovery with topical ofloxacin and glucocorticoid treatment. Bacteriology of an ear swab yielded a pure culture of corynebacteria, which could not be identified at the species level using routine methods. However, the 16S rRNA gene sequence was 100% identical to the recently published novel corynebacterium species, Corynebacterium provencense. Whole genome sequencing of the cat isolate and calculation of average nucleotide identity (99.1%) confirmed this finding. The cat isolate was found to contain additional presumptive iron acquisition genes that are likely to encode virulence factors. Furthermore, the strain tested resistant to clindamycin, penicillin and ciprofloxacin. The cat was subsequently treated with chloramphenicol, which lead to clinical improvement. CONCLUSION: Corynebacteria from otitis cases are not routinely identified at the species level and not tested for antimicrobial susceptibility in veterinary laboratories, as they are not considered major pathogens. This may lead to underreporting of this genus or animals being treated with inappropriate antimicrobials since corynebacteria are often resistant to multiple drugs.

Clinical profile and outcome of children with scrub typhus from Chennai, South India.

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. We prospectively studied the clinico-laboratory profile and outcome of 358 children aged 1 day to 18 years diagnosed with scrub typhus from Chennai, South India. All children (100%) had fever. Eschar was seen in 67%. All children were treated with oral doxycycline and those with complications were treated with intravenous chloramphenicol/azithromycin. Rapid defervescence (within 48 h) after initiation of doxycline was seen in 306 (85%) and 52 (14.5%) developed complications. Multivariate logistic regression analysis revealed that children who had an elevated aspartate amino transferase (> 120 IU/L) and the presence of thrombocytopenia (platelet count less than 1 lac cells/mm3) at admission had high risk of developing complications. The overall mortality rate in this series was 0.8%. CONCLUSION: Our 4-year study highlights the clinico-laboratory profile of Scrub typhus in children from Chennai, South India. Early recognition and prompt treatment reduces the complication and mortality. What is Known: • Scrub typhus is endemic to tsutsugamushi triangle, a geographical triangle extending from northern Japan in the east to Pakistan and Afghanistan in the west and northern Australia in the south. • There is paucity of data regarding its clinico-laboratory profile in neonates as well as its predictors of outcome. What is New: • Children who had an elevated AST and the presence of thrombocytopenia at admission had high risk of developing complications.

Antibiotics for treating scrub typhus.

BACKGROUND: Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin. OBJECTIVES: To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus. SEARCH METHODS: We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test). DATA COLLECTION AND ANALYSIS: For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis. MAIN RESULTS: We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs. AUTHORS' CONCLUSIONS: Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.

Interactions between Chloramphenicol, Carrier Polymers, and Bacteria-Implications for Designing Electrospun Drug Delivery Systems Countering Wound Infection.

Antibacterial drug-loaded electrospun nano- and microfibrous dressings are of major interest as novel topical drug delivery systems in wound care. In this study, chloramphenicol (CAM)-loaded polycaprolactone (PCL) and PCL/poly(ethylene oxide) (PEO) fiber mats were electrospun and characterized in terms of morphology, drug distribution, physicochemical properties, drug release, swelling, cytotoxicity, and antibacterial activity. Computational modeling together with physicochemical analysis helped to elucidate possible interactions between the drug and carrier polymers. Strong interactions between PCL and CAM together with hydrophobicity of the system resulted in much slower drug release compared to the hydrophilic ternary system of PCL/PEO/CAM. Cytotoxicity studies confirmed safety of the fiber mats to murine NIH 3T3 cells. Disc diffusion assay demonstrated that both fast and slow release fiber mats reached effective concentrations and had similar antibacterial activity. A biofilm formation assay revealed that both blank matrices are good substrates for the bacterial attachment and formation of biofilm. Importantly, prolonged release of CAM from drug-loaded fibers helps to avoid biofilm formation onto the dressing and hence avoids the treatment failure.

Antibiotic prophylaxis for episiotomy repair following vaginal birth.

BACKGROUND: Bacterial infections occurring during labour, childbirth, and the puerperium may be associated with considerable maternal and perinatal morbidity and mortality. Antibiotic prophylaxis might reduce wound infection incidence after an episiotomy, particularly in situations associated with a higher risk of postpartum perineal infection, such as midline episiotomy, extension of the incision, or in settings where the baseline risk of infection after vaginal birth is high. However, available evidence is unclear concerning the role of prophylactic antibiotics in preventing infections after an episiotomy. OBJECTIVES: To assess whether routine antibiotic prophylaxis before or immediately after incision or repair of episiotomy for women with an uncomplicated vaginal birth, compared with either placebo or no antibiotic prophylaxis, prevents maternal infectious morbidities and improves outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, LILACS, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) on 24 July 2017, and screened reference lists of retrieved studies. SELECTION CRITERIA: We considered randomised controlled trials, quasi-randomised trials, and cluster-randomised trials that compared the use of routine antibiotic prophylaxis for incision or repair of an episiotomy for women with otherwise normal vaginal births, compared with either placebo or no antibiotic prophylaxis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. We only found one quasi-randomised trial that met the inclusion criteria and was included in the analysis, therefore, we did not perform a meta-analysis. MAIN RESULTS: We included one quasi-RCT (with data from 73 women) in the review. The trial, which was conducted in a public hospital in Brazil, compared oral chloramphenicol 500 mg four times daily for 72 hours after episiotomy repair (N = 34) and no treatment (N = 39). We assessed most of the domains at high risk of bias because women were randomised according to even and odd numbers, allocation concealment was based on protocol number, there was no treatment or placebo administered in the control group, we were unclear about the blinding of outcome assessments, and outcomes were incompletely reported. We considered the other domains to be at low risk of bias. We downgraded the quality of the evidence for very serious design limitations (related to lack of random sequence generation, allocation concealment, and blinding) and imprecision of effect estimates (small sample sizes and wide confidence intervals (CI) of effect estimates).We found very low-quality evidence, from one trial of 73 women, that there was no clear indication that prophylactic antibiotics reduced the incidence of episiotomy wound dehiscence with infection (risk ratio (RR) 0.13, 95% CI 0.01 to 2.28), or without infection (RR 0.82, 95% CI 0.29 to 2.34). No cases of other puerperal infections (e.g. endometritis) were reported in either the antibiotic or control group.The trial did not report on any of the secondary outcomes of interest for this review, including severe maternal infectious morbidity, discomfort or pain at the episiotomy wound site, sexual function postpartum, adverse effects of antibiotics, costs of care, women's satisfaction with care, and individual antimicrobial resistance. AUTHORS' CONCLUSIONS: There was insufficient evidence to assess the clinical benefits or harms of routine antibiotic prophylaxis for episiotomy repair after normal birth. The only trial included in this review had several methodological limitations, with very serious limitations in design, and imprecision of effect estimates. In addition, the trial tested an antibiotic with limited application in current clinical practice. There is a need for a careful and rigorous assessment of the comparative benefits and harms of prophylactic antibiotics on infection morbidity after episiotomy, in well-designed randomised controlled trials, using common antibiotics and regimens in current obstetric practice.

Pre-admission antibiotics for suspected cases of meningococcal disease.

BACKGROUND: Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis. OBJECTIVES: To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure, and morbidity in people suspected of meningococcal disease. SEARCH METHODS: We searched CENTRAL (6 January 2017), MEDLINE (1966 to 6 January 2017), Embase (1980 to 6 January 2017), Web of Science (1985 to 6 January 2017), LILACS (1982 to 6 January 2017), and prospective trial registries to January 2017. We previously searched CAB Abstracts from 1985 to June 2015, but did not update this search in January 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial and so did not perform data synthesis. We assessed the overall quality of the evidence using the GRADE approach. MAIN RESULTS: We found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to 2.15; N = 477; 18 clinical failures; moderate-quality evidence), or neurological sequelae (RR 1.29, 95% CI 0.63 to 2.62; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae. AUTHORS' CONCLUSIONS: We found no reliable evidence to support the use pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Moderate-quality evidence from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe, and economical in reducing serious outcomes. The choice between these antibiotics should be based on affordability, availability, and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justified in people with less severe illness, and are needed to provide reliable evidence in different clinical settings.

Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its relationship with their maternal background and neonatal health.

Few clinical studies have determined the quantitative transfer of vaginal chloramphenicol to circulating blood in pregnant women. This study aimed to evaluate the plasma concentration of chloramphenicol in pregnant women treated with trans-vaginal tablets and its relationship with maternal background and neonatal health. Thirty-seven pregnant women treated with 100 mg of trans-vaginal chloramphenicol once daily for bacterial vaginosis and its suspected case were enrolled. The plasma concentration of chloramphenicol was determined using liquid chromatography coupled to tandem mass spectrometry at day 2 or later after starting the medication. The correlations between the maternal plasma concentration of chloramphenicol and the background and neonatal health at birth were investigated. Chloramphenicol was detected from all maternal plasma specimens and its concentration ranged from 0.043 to 73.1 ng/mL. The plasma concentration of chloramphenicol declined significantly with the administration period. The plasma concentration of chloramphenicol was lower at the second than the first blood sampling. No correlations were observed between the maternal plasma concentration of chloramphenicol and background such as number of previous births, gestational age at dosing, and clinical laboratory data. Neonatal infant health parameters such as birth-weight, Apgar score at birth, and gestational age at the time of childbearing were not related to the maternal plasma concentration of chloramphenicol. Vaginal chloramphenicol transfers to circulating blood in pregnant women. The maternal plasma concentration of chloramphenicol varied markedly and was associated with the administration day, but not with maternal background or her neonatal health.