Antimicrobial for 7 or 14 Days for Febrile Urinary Tract Infection in Men: A Multicenter Noninferiority Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND: The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial. METHODS: To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events. RESULTS: Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, -21.9 [95% confidence interval, -33.3 to -10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups. CONCLUSIONS: A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended. CLINICAL TRIALS REGISTRATION: NCT02424461; Eudra-CT: 2013-001647-32.

With and without exogenous biological scaffolds for repairing traumatic perforations of tympanic membrane: Randomized clinical trials.

OBJECTIVE: The objective of this study was to compare the efficacy of ofloxacin ear drops, vaseline gauze (VG) and dry gelfoam alone on the large traumatic perforations of tympanic membrane (TM). MATERIAL AND METHODS: A randomized prospective analysis was performed for the treatment of traumatic perforation larger than 25 % of the entire TM. The closure rate, closure time, and hearing gain between ofloxacin ear drops, VG and gelfoam alone groups were compared at 3 months. RESULTS: Final analysis was performed on 70 patients. The closure rates of perforation in the ofloxacin ear drops, VG, and dry gelfoam patch groups were 100.0 %, 92.0 %, and 87.5 %, respectively (P = 0.41).The mean closure times were 8.67 ± 3.1, 10.65 ± 4.2, and 14.33 ± 7.5 days for the ofloxacin ear drops, VG, and gelfoam patch alone groups, respectively. The closure times among the 3 groups were significantly different (P = 0.003). In addition, there was a significant difference between the ofloxacin ear drops and gelfoam patch alone groups with regard to closure time (P = 0.003), while there was no significant difference between the ofloxacin ear drops and VG groups (P = 0.080) or VG and gelfoam patch groups (P = 0.056).The mean hearing gain was 11.4 ± 2.3 dB for the ofloxacin ear drops group, 11.7 ± 4.1 dB for the VG group, and 12.2 ± 1.6 dB for the gelfoam patch group (P = 0.69). CONCLUSIONS: The repairing of traumatic perforations didn't require an exogenous biological scaffold. Ofloxacin ear drops and VG were a deal material for repairing traumatic perforation in otology clinic, which not only was readily available and inexpensive but also showed faster closure compared with dry gelfoam alone.

Comparative study of fibroblast growth factor 2 and ofloxacin ear drops for repairing large traumatic perforations: A randomized controlled study.

OBJECTIVE: The objective of this study was to compare the healing outcome of fibroblast growth factor 2 (FGF2), ofloxacin ear drops (OFLX) and spontaneous healing for repairing large traumatic tympanic membrane (TM) perforations. MATERIAL AND METHODS: A total of 75 traumatic large perforations with >1/4 of TM were randomly divided into FGF2 (n = 25), OFLX (n = 25), and spontaneous healing (n = 25) groups. The closure rates, closure times, and hearing gains were compared at 3 months. RESULTS: At 2 weeks after treatment, the closure rate was 95.8 % in the FGF2 group, 96.0 % in the ofloxacin ear drops group, and 14.3 % in the spontaneous healing group (P < 0.01), respectively. At 3 months after treatment, the closure rate was 100 % in the FGF2 group, 100 % in the OFLX group, and 85.7 % in the spontaneous healing group, no among-group differences were significant (P > 0.05). The mean closure time was 9.69 ± 2.46 days in the FGF2 group, 9.45 ± 2.32 days in the OFLX group, and 30.94 ± 8.95 days in the spontaneous healing group (P < 0.01). The mean ABG was 10.37 ± 2.51 dB for the FGF2 group, 11.01 ± 1.31 dB for the OFLX group, and 10.86 ± 1.94 dB for the spontaneous healing group, no significant difference was found among three groups (P > 0.05). CONCLUSIONS: This study suggested that both FGF2 and OFLX significantly shortened the mean closure time and improved the closure rate compared with spontaneous healing for repairing large traumatic perforations, while the healing outcome wasn't significantly different among FGF2 and OFLX groups.

Ofloxacin-loaded HMPB NPs for Klebsiella pneumoniae eradication in the surgical wound with the combination of PTT.

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium whose drug-resistant can cause surgical failures and incurable infections in hospital patients. Thus, how to reverse or delay the resistance induction has become a great challenge for development antiresistant drug. Recently, the combination of nanomaterial-loaded antibiotics with photothermal therapy showed the efficient antibacteria ability under a low dosage of antibiotics. In this study, a nanocomposite of HMPB NPs with inherent photothermal therapy capability was used to eradicate K. pneumoniae after loading with Ofloxacin, an antibiotic against K. pneumoniae in vitro and in vivo. The nanocomplexes named as Ofloxacin@HMPB@HA NPs showed a higher effect against K. pneumoniae by destroying cell integrity and inducing ATP leakage with the assistance of laser irradiation, compared with sole Ofloxacin@HMPB@HA NPs or laser irradiation. Surgical wound infection assay further demonstrated the efficient killing K. pneumoniae and promoting the formation of new tissues, as well, which was reflected by the rapid healing of surgical wound. In summary, these results indicate the great potential of this combinational tactic based on Ofloxacin@HMPB@HA NPs for preventing the failure caused by K. pneumoniae infection.

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.

Drug Resistance (Dapsone, Rifampicin, Ofloxacin) and Resistance-Related Gene Mutation Features in Leprosy Patients: A Systematic Review and Meta-Analysis.

Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.

Aqueous Humour Ofloxacin Concentration after Topical Instillation in Patients with Dry Eye Disease.

Background and Objectives: A prospective, randomized clinical trial was conducted to evaluate the concentration of ofloxacin in the aqueous humour (AqH) of patients suffering from dry eye disease (DED) after topical instillation. Materials and Methods: Ninety-one (91) cataract patients scheduled for phacoemulsification were categorized into three groups according to DED severity. Group I (n = 17) was comprised of subjects without DED, patients in group II (n = 37) were evaluated as having non-severe DED, while group III (n = 37) consisted of patients suffering from severe DED. Preoperatively, patients received 4 drops of 0.3% of ofloxacin at 15 min intervals. One hour after the last instillation, aqueous samples were collected intraoperatively. Results: The median AqH concentration of ofloxacin in group I was 199.9 ng/mL (range 92.2−442.8 ng/mL), while in group II it was 530.5 ng/mL (range 283.7−1004.9 ng/mL), and 719.2 ng/mL (range 358.0−1512.4 ng/mL) in Group III, p < 0.001 (Kruskal-Wallis tests). Pairwise tests (two-tailed with Bonferroni corrections) between groups resulted in a p-value of 0.001 when group II was compared to group I and group III was compared to group I, and a p-value of 0.020 when group II was compared to group III. The severity of DED, across groups I, II, and III, and the levels of ofloxacin revealed a strong positive correlation (r = 0.639, p < 0.001). Conclusions: Ofloxacin concentration in the AqH after topical drop instillation may be affected by the degree of ocular surface inflammation in patients suffering from DED.

Ofloxacin-Containing Multidrug Therapy in Ambulatory Leprosy Patients: A Case Series.

BACKGROUND: Standard dapsone and clofazimine-containing multidrug therapy (MDT) for leprosy is limited by drug tolerability, which poses treatment adherence barriers. Although ofloxacin-based regimens are promising alternatives, current efficacy and safety data are limited, particularly outside of endemic areas. We evaluated treatment outcomes in patients with leprosy receiving ofloxacin-containing MDT (OMDT) at our center. METHODS: We performed a retrospective chart review of patients treated for leprosy at our center over an 8-year period (2011-2019). Primary outcomes evaluated were clinical cure rate, occurrence of leprosy reactions, antibiotic-related adverse events, and treatment adherence. Analyses were descriptive; however, data were stratified by age, sex, spectrum of disease, region of origin, and treatment regimen, and odds ratios were reported to assess associations with adverse outcomes. RESULTS: Over the enrolment period, 26 patients were treated with OMDT (n = 19 multibacillary, n = 7 paucibacillary), and none were treated with clofazimine-based standard MDT. At the time of analysis, 23 patients (88%) had completed their course of treatment, and all were clinically cured, while 3 (12%) were still on treatment. Eighteen patients (69%) experienced either ENL (n = 7, 27%), type 1 reactions (n = 7, 27%), or both (n = 4, 15%). No patients stopped ofloxacin due to adverse drug effects, and there were no cases of allergic hypersensitivity, tendinopathy or rupture, or C. difficile colitis. CONCLUSIONS: We demonstrate a high cure rate and tolerability of OMDT in this small case series over an 8-year period, suggesting its viability as an alternative to standard clofazimine-containing MDT.

Chronic suppurative otitis media due to Streptomyces cacaoi, the second case report in human infection.

BACKGROUND: Streptomyces cacaoi, Gram-positive, branched, filamentous bacillus forms without fragmentation, are saprophytic soil organisms rarely known to cause invasive infections other than mycetoma. Here we describe a case of chronic suppurative otitis media caused by Streptomyces cacaoi in a patient with hyperlipidemia in China. CASE PRESENTATION: A 62-year-old female patient with hyperlipidemia suffered chronic suppurative otitis media caused by Streptomyces cacaoi. She had a favorable outcome with a 4-week course of ofloxacin ear drops. CONCLUSIONS: Streptomyces cacaoi is rarely reported to cause human infection. The introduction of molecular techniques improves the ability to identify rare species such as Streptomyces considerably. We report the case improve our ability to identify this pathogen and expand the range of known bacterial causes of human infection.

Outbreak of acute undifferentiated febrile illness in Kathmandu, Nepal: clinical and epidemiological investigation.

BACKGROUND: Outbreaks of acute undifferentiated febrile illness (AUFI) are common in Nepal, but the exact etiology or risk factors for them often go unrecognized. Diseases like influenza, enteric fever and rickettsial fevers account for majority of such outbreaks. Optimal diagnostic tests to inform treatment decisions are not available at the point-of-care. A proper epidemiological and clinical characterization of such outbreaks is important for appropriate treatment and control efforts. METHODS: An investigation was initiated as a response to increased presentation of patients at Patan Hospital from Chalnakhel locality in Dakchinkali municipality, Kathmandu with AUFI from June 10 to July 1, 2016. Focused group discussion with local inhabitants and the epidemiological curve of febrile patients at local primary health care centre confirmed the outbreak. The household-survey was conducted in the area with questionnaire administered on patients to characterize their illnesses and their medical records were reviewed. A different set of questionnaire was administered on the patients and controls to investigate the association with common risk factors. Water samples were collected and analyzed microbiologically. RESULTS: Eighty one patients from 137 households suffered from febrile illness within 6 weeks window before the investigation. All the 67 sampled patients with acute fever had a generalized illness without a discernible focus of infection. Only 38% of the patients had received a clinical diagnosis while the rest were treated empirically without a diagnosis. Three patients had blood culture confirmed enteric fever. Forty-two (63%) patients had been administered antibiotics, most commonly, ofloxacin, cefixime or azithromycin with a mean fever clearance time of 4 days. There was no definite association between several risk factors and fever. Fecal contamination was noted in tap water samples. CONCLUSION: Based on the pattern of illness, this outbreak was most likely a mixture of self-limiting viral infections and enteric fever. This study shows that even in the absence of a confirmed diagnosis, a detailed characterization of the illness at presentation and the recovery course can suggest the diagnosis and help in formulating appropriate recommendation for treatment and control.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Machine learning for classifying tuberculosis drug-resistance from DNA sequencing data.

Motivation: Correct and rapid determination of Mycobacterium tuberculosis (MTB) resistance against available tuberculosis (TB) drugs is essential for the control and management of TB. Conventional molecular diagnostic test assumes that the presence of any well-studied single nucleotide polymorphisms is sufficient to cause resistance, which yields low sensitivity for resistance classification. Summary: Given the availability of DNA sequencing data from MTB, we developed machine learning models for a cohort of 1839 UK bacterial isolates to classify MTB resistance against eight anti-TB drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, ciprofloxacin, moxifloxacin, ofloxacin, streptomycin) and to classify multi-drug resistance. Results: Compared to previous rules-based approach, the sensitivities from the best-performing models increased by 2-4% for isoniazid, rifampicin and ethambutol to 97% (P < 0.01), respectively; for ciprofloxacin and multi-drug resistant TB, they increased to 96%. For moxifloxacin and ofloxacin, sensitivities increased by 12 and 15% from 83 and 81% based on existing known resistance alleles to 95% and 96% (P < 0.01), respectively. Particularly, our models improved sensitivities compared to the previous rules-based approach by 15 and 24% to 84 and 87% for pyrazinamide and streptomycin (P < 0.01), respectively. The best-performing models increase the area-under-the-ROC curve by 10% for pyrazinamide and streptomycin (P < 0.01), and 4-8% for other drugs (P < 0.01). Availability and implementation: The details of source code are provided at http://www.robots.ox.ac.uk/~davidc/code.php. Contact: david.clifton@eng.ox.ac.uk. Supplementary information: Supplementary data are available at Bioinformatics online.

Underlying mechanisms of leprosy recurrence in the Western Amazon: a retrospective cohort study.

BACKGROUND: The multidrug therapy (MDT) for leprosy treatment adopted by Brazil in the 1990s was important for reducing leprosy in the country; however, recurrent cases remained problematic. Mechanisms involved in leprosy recurrence are heterogeneous and can be sorted into three groups: insufficient therapy, bacillary persistence and new infections. This study aimed to analyse the time interval of leprosy recurrence in relation to the therapeutic scheme in the state of Acre. The hypotheses were as follows: 1) treatments (a) rifampicin, ofloxacin and minocycline (ROM) and (b) dapsone (DDS) have a short leprosy recurrence time, 2) treatments based on MDT have a long leprosy recurrence time, 3) there is a dose-response relationship between MDT and the time interval between leprosy episodes. METHODS: This retrospective cohort study included 201 patients with a second episode of clinical leprosy at the reference centers for leprosy control in the state of Acre. Exposure was the type of therapeutic scheme as follows: 1) ROM, 2) DDS, 3) MDT0-9 doses, 4) MDT10-19 doses, 5) MDT20-29 doses, and 6) MDT30+ doses. Outcome was the time interval between release from treatment and a diagnosis of a recurrent leprosy case. Incidence rate ratios and relative risk Poisson regressions adjusted by age and sex were calculated with 95% confidence intervals. RESULTS: The 201 patients studied during this retrospective follow-up resulted in a total of 224 cases of recurrent leprosy. Incidence rate ratios within this therapeutic scheme were as follows: 3.3 (2.39, 4.2; ROM/MDT30+), 1.12 (0.33, 1.92; DDS/MDT30+), 2.17 (1.39, 2.94; MDT0-9/MDT30+), 1.94 (1.13, 2.75; MDT10-19/MDT30+) and 1.26 (0.47, 2.05; MDT20-29/MDT30+). Relative risk Poisson regressions showed a protective effect of MDT30+ in comparison with ROM (0.22; 0.07, 0.72), MDT0-9 (0.42; 0.21, 0.85), and MDT10-19 (0.44; 0.21, 0.92). No differences among MDT30+ and DDS (0.71; 0.36, 1.41) and MDT20-29 (0.76; 0.38, 1.49) were observed. CONCLUSIONS: New infection is an important-yet neglected-mechanism in leprosy recurrence in the state of Acre and can challenge the leprosy elimination plan in Brazil. MDT with few doses might be associated with leprosy recurrence due to insufficient therapy or bacillary persistence.

Antibiotics for treating urogenital Chlamydia trachomatis infection in men and non-pregnant women.

BACKGROUND: The genital infection caused by Chlamydia trachomatis (CT) is a common sexually transmitted infection (STI) globally. The infection is mainly asymptomatic in women, thus it can produce infertility and chronic pelvic pain. In men infection is mainly symptomatic, but can evolve to prostatitis. Clinical practice guidelines for CT urogenital infections do not give any specific recommendation about which antibiotic use as first option OBJECTIVES: To assess the efficacy and safety of antibiotic treatment for CT genital infection in men and non-pregnant women. SEARCH METHODS: The Cochrane Sexually Transmitted Infections' (STI) Information Specialist developed the electronic searches in electronic databases (CENTRAL, MEDLINE, Embase and LILACS), and trials registers. We searched studies published from inception to June 2018. SELECTION CRITERIA: We included parallel, randomised controlled trials (RCTs) of men, and sexually-active, non-pregnant women with CT infection (urethritis or uterine cervicitis or asymptomatic), diagnosed by cell culture for CT, nucleic acid amplification tests (NAAT) or antigen-based detection methods, who had been treated with any of the antibiotic regimens recommended by any of the updated to 2013 CT Guidelines. DATA COLLECTION AND ANALYSIS: Four review authors screened evidence according to selection criteria and independently extracted data and assessed risk of bias. Two authors developed the 'Summary of findings' tables. We used a fixed-effect meta-analysis model for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect. We estimated the pooled risk ratio in order to establish the effects of the comparisons. Our primary outcomes were microbiological failure and adverse events, and our secondary outcomes were clinical failure, antimicrobial resistance and reinfection. MAIN RESULTS: We selected 14 studies ( 2715 participants: 2147 (79.08%) men and 568 (20.92%) women). The studies were conducted mainly at STD clinics. Sample sizes ranged from 71 to 606 participants; follow-up was 29.7 days on average.For the comparison: azithromycin single dose versus doxycycline once or twice daily for 7 days, in men treated for CT, the risk of microbiological failure was higher in the azithromycin group (RR 2.45, 95% CI 1.36 to 4.41; participants = 821; studies = 9; moderate-quality evidence), but regarding clinical failure, the results showed that the effect is uncertain (RR 0.94, 95% CI 0.43 to 2,05; I² = 55%; participants = 525; studies = 3; low-quality evidence). Regarding adverse events (AE) in men there could be little or no difference between the antibiotics (RR 0.83, 95% CI 0.67 to 1.02; participants = 1424; studies = 6; low-quality evidence). About women treated for CT, the effect on microbiological failure was uncertain (RR = 1.71, 95% CI 0.48 to 6.16; participants = 338; studies = 5; very low-quality evidence). There were no studies assessing clinical failure or adverse events in women, however, we found that azithromycin probably has fewer adverse events in both genders (RR 0.83, 95% CI 0.71 to 0.98; I² = 0%; participants = 2261; studies = 9; moderate-quality evidence).For the second comparison: doxycycline compared to ofloxacin, for men treated for CT the effect on microbiological failure was uncertain (RR 8.53, 95% CI 0.43 to 167.38, I² not applicable; participants = 80; studies = 2; very low-quality evidence), as also it was on clinical failure (RR 0.85, 95% CI 0.28 to 2.62; participants = 36; studies = 1; very low-quality evidence). The effect of in women on clinical failure was uncertain (RR 0.94, 95% CI 0.39 to 2.25; I² = 39%; participants = 127; studies = 2; very low-quality evidence).Regarding adverse events, the effect in both men and women was uncertain (RR 1.02 95% CI 0.66 to 1.55; participants = 339 studies = 3; very low-quality evidence). The effect on microbiological failure in women and in men and women together, the effect on microbiological failure was not estimable. The most frequently AE reported were not serious and of gastrointestinal origin.No studies assessed antimicrobial resistance or reinfection in either comparison. AUTHORS' CONCLUSIONS: In men, regimens with azithromycin are probably less effective than doxycycline for microbiological failure, however, there might be little or no difference for clinical failure. For women, we are uncertain whether azithromycin compared to doxycycline increases the risk of microbiological failure. Azithromycin probably slightly reduces adverse events compared to doxycycline in men and women together but may have little difference in men alone. We are uncertain whether doxycycline compared to ofloxacin reduces microbiological failure in men or women alone, or men and women together, nor if it reduces clinical failure or adverse events in men or women.Based on the fact that women suffer mainly asymptomatic infections, and in order to test the effectiveness and safety of the current recommendations (azithromycin, doxycycline and ofloxacin), for CT infection, especially in low and middle income countries, future RCTs should be designed and conducted to include a large enough sample size of women, and with low risk of bias. It is also important that future RCTs include adherence, CT resistance to antibiotic regimens, and risk of reinfection as outcomes to be measured. In addition, it is important to conduct a network meta-analysis in order to evaluate all those studies that included in one arm only the current antibiotic treatments for CT infection that are recommended by the updated clinical practice guidelines.

Comparison of the medical costs and effects of large traumatic eardrum perforations treatment.

OBJECTIVE: We investigated the medical costs and effects of ofloxacin drops (OFLX), gelatin sponge patches, spontaneous healing, and endoscopic myringoplasty on healing in large tympanic membrane perforations (TMPs). METHODS: In total, 100 patients with large traumatic TMPs involving >50% of the eardrum were randomly assigned to OFLX, gelatin sponge, spontaneous healing, or endoscopic myringoplasty treatment groups. Medical costs, closure times, and closure rates were compared among groups at 6 months. RESULTS: The closure rates in the OFLX, gelatin sponge, spontaneous healing, and endoscopic myringoplasty groups were 95.7%, 82.6%, 58.3%, and 91.7%, respectively (P = 0.05). The mean closure time was 13.73 ±â€¯6.14 days in the OFLX group, 15.89 ±â€¯4.95 days in the gelatin sponge group, 48.36 ±â€¯10.37 days in the spontaneous healing group, and 12 days in the endoscopic myringoplasty group (P < 0.001). The mean medical costs in US dollars were $15.53 ±â€¯3.15, $103.64 ±â€¯111.58, $11.17 ±â€¯1.33, and $715.90 in the OFLX, gelatin sponge, spontaneous healing, and endoscopic myringoplasty groups, respectively (P < 0.001). CONCLUSION: Although the gelatin sponge and myringoplasty treatments significantly shortened the closure time compared with spontaneous healing, the gelatin sponge patch did not significantly improve the closure rate, and the medical cost of myringoplasty was significantly higher than that of the other treatments. In contrast, OFLX significantly shortened closure time and had a higher closure rate than spontaneous healing, and the medical costs were lower than those of the gelatin sponge and myringoplasty procedures.

Cefixime-ofloxacin Combination in the Management of Uncomplicated Typhoid Fever in the Indian Community Setting.

Antimicrobial resistance is a global problem and is definitely a cause of concern in India too, in the context of typhoid fever. It is becoming clearer that monotherapy is not effective for typhoid fever and the option to be considered is combination therapy. There are very few antibiotic combinations that are approved and backed by clinical evidence, available in India for the treatment of typhoid fever. Cefixime-ofloxacin combination is approved by Indian Regulatory Authority and has a good body of clinical evidence in the current Indian context. In-silico studies have demonstrated positive rationale of combining these two drugs, while in-vitro studies have substantiated the same by showing a strain specific synergistic and or additive activity between the two drugs against S. typhi. Clinical studies in Indian patients have shown multiple benefits of using this combination in typhoid fever such as a quick time to defervescence (~3 days), complete clinical cure in ~7 days, effective symptomatic relief, efficacy in relapse cases and a reduced need for hospitalization. The drug combination also demonstrates a very good tolerability profile. Recommendations of the Association of physicians of India also back this combination in typhoid fever. Thus, in the current era of emerging antibiotic resistance, cefixime-ofloxacin is a safe, effective and reliable treatment option for clinicians to treat uncomplicated typhoid in the Indian community setting.

Leprosy in Nonimmigrant Canadian Man without Travel outside North America, 2014.

In Canada, Hansen disease (leprosy) is rare and not considered in diagnoses for nonimmigrant patients. We report Mycobacterium leprae infection in a Canadian man whose sole travel was to Florida, USA. The M. leprae isolate was identified as armadillo-associated genotype 3I-2-v1. Travelers to the southern United States should avoid contact with armadillos.

Limited Effect of Later-Generation Fluoroquinolones in the Treatment of Ofloxacin-Resistant and Moxifloxacin-Susceptible Multidrug-Resistant Tuberculosis.

Recent data conflict on the clinical efficacy of later-generation fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but susceptible to moxifloxacin. The purpose of the present study was to evaluate whether later-generation fluoroquinolones can improve treatment outcomes in patients with ofloxacin-resistant, moxifloxacin-susceptible MDR-TB. A retrospective cohort study was performed on 208 patients with moxifloxacin-susceptible MDR-TB who were treated between 2006 and 2011. Later-generation fluoroquinolones were used for all patients. Overall, 171 patients (82%) had ofloxacin-susceptible, moxifloxacin-susceptible MDR-TB (ofloxacin-susceptible group), and 37 (18%) had ofloxacin-resistant, moxifloxacin-susceptible MDR-TB (ofloxacin-resistant group). Compared to the ofloxacin-susceptible group, the ofloxacin-resistant group was more likely to have a history of MDR-TB treatment (P < 0.001) and cavitary lesions on chest radiography (P < 0.001). In addition, the ofloxacin-resistant group was more likely than the ofloxacin-susceptible group to have resistance to the drugs pyrazinamide (P = 0.003), streptomycin (P = 0.015), prothionamide (P < 0.001), and para-aminosalicylic acid (P < 0.001). Favorable outcomes were more frequently achieved for the ofloxacin-susceptible group than for the ofloxacin-resistant group (91% [156/171] versus 57% [21/37], respectively [P < 0.001]). In multivariable regression logistic analysis, the ofloxacin-susceptible group was about 5.36 (95% confidence interval, 1.55 to 18.53) times more likely than the ofloxacin-resistant group (P < 0.001) to have favorable outcomes. Despite in vitro moxifloxacin susceptibility, the frequency of favorable treatment outcomes for ofloxacin-resistant MDR-TB was significantly lower than that for ofloxacin-susceptible MDR-TB, even when later-generation fluoroquinolones were used, indicating that more-aggressive therapies may be needed for ofloxacin-resistant MDR-TB.

Gonococcal and Chlamydial Cases of Pelvic Inflammatory Disease at 2 Canadian Sexually Transmitted Infection Clinics, 2004 to 2014: A Retrospective Cross-sectional Review.

One hundred thirteen patients with gonococcal and chlamydial pelvic inflammatory disease were reviewed at 2 Canadian sexually transmitted infection clinics. Most patients (81%) with pelvic inflammatory disease were diagnosed as having chlamydia alone. Three treatment failures were seen in patients treated with ofloxacin.

Molecular characterization of mutations associated with resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients from high prevalence tuberculosis city in Morocco.

BACKGROUND: The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised public health concern for global TB control. Although multi drug-resistant tuberculosis (MDR- TB) prevalence and associated genetic mutations in Morocco are well documented, scarce information on XDR TB is available. Hence, the evaluation of pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drugs, is of great value for better management of M/XDR TB in Morocco. OBJECTIVES: To evaluate pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drug resistance, in 703 clinical isolates from TB patients recruited in Casablanca, and to assess the usefulness of molecular tools in clinical laboratories for better management of M/XDR TB in Morocco. METHODS: Drug susceptibility testing (DST) was performed by the proportional method for first line drugs, and then the selected MDR isolates were tested for second line drugs (Ofloxacin, Kanamycin, Amikacin and Capreomycin). Along with DST, all samples were subjected to rpoB, katG and p-inhA mutation analysis by PCR and DNA sequencing. MDR isolates as well as 30 pan-susceptible strains were subjected to PCR and DNA sequencing of gyrA, gyrB, rrs, tlyA genes and eis promoter, associated with resistance to fluoroquinolones and injectable drugs. RESULTS: Among the 703 analysed strains, 12.8% were MDR; Ser531Leu and Ser315Thr being the most common recorded mutations within rpoB and katG genes associated with RIF and INH resistance respectively. Drug susceptibility testing for second line drugs showed that among the 90 MDR strains, 22.2% (20/90) were resistant to OFX, 2.22% (2/90) to KAN, 3.33% (3/90) to AMK and 1.11% (1/90) to CAP. Genotypic analysis revealed that 19 MDR strains harbored mutations in the gyrA gene; the most recorded mutation being Asp91Ala accounting for 47.6% (10/21), and 2 isolates harbored mutations in the promoter region of eis gene. No mutation was found in gyrB, rrs and tlyA genes. Moreover, none of the pan-susceptible isolates displayed mutations in targeted genes. CONCLUSION: Most of mutations associated with SLD resistance occurred in gyrA gene (codons 90-94) and eis promoter region. These findings highlight the impact of mutations in gyrA on the development of fluroquinolones resistance and provide the first estimates of the proportion of pre-XDR-TB among MDR-TB cases in Morocco.