OBJECTIVES: The aim was to evaluate the efficacy and tolerability of gentamicin 240 mg plus azithromycin 2 g for treatment of uncomplicated rectal and pharyngeal gonorrhoea compared to ceftriaxone 500 mg plus azithromycin 2 g, the recommended European first-line gonorrhoea treatment. METHODS: A non-inferiority, open-label, single-centre randomized controlled trial was conducted in Prague, Czech Republic. Patients, 18-75 years of age, diagnosed with uncomplicated rectal or pharyngeal gonorrhoea by nucleic acid amplification test (NAAT) were randomized to treatment with gentamicin 240 mg intramuscularly plus azithromycin 2 g orally or ceftriaxone 500 g intramuscularly plus azithromycin 2 g orally. The primary outcome was negative culture and negative NAAT, i.e. 1 week and 3 weeks, respectively, after treatment. RESULTS: Both clinical cure and microbiological clearance was achieved by 100% (95% CI 0.95-1.00) of patients in the gentamicin/azithromycin arm (n = 72; 40 rectal, 17 pharyngeal and 15 rectal+pharyngeal infections both localizations) and 100% (95% CI 0.95-1.00) in ceftriaxone/azithromycin arm (n = 71; 38 rectal, 14 pharyngeal and 19 rectal+pharyngeal infections). The absolute difference between the two arms was 0.0% (CI95% -5.1 to 5.1), thus less than the pre-specified margin of 7%. Administration of gentamicin was not more painful than ceftriaxone according to the visual analogue scale (1.8 vs. 3.4; p <0.001). Gastrointestinal adverse events were similar in the ceftriaxone arm (33/71, 46.5%) and the gentamicin arm (29/72, 40.3%), and overall in most (52/62, 83.9%) cases they were mild. CONCLUSIONS: Gentamicin 240 mg plus azithromycin 2 g is an effective alternative for treatment of extragenital gonorrhoea.

• Klíčová slova
• Azithromycin, Ceftriaxone, Gentamicin, Neisseria gonorrhoeae, Treatment,
• MeSH
• antibakteriální látky aplikace a dávkování   škodlivé účinky   MeSH
• aplikace orální MeSH
• azithromycin aplikace a dávkování   škodlivé účinky   MeSH
• ceftriaxon aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• farynx mikrobiologie   MeSH
• gentamiciny aplikace a dávkování   škodlivé účinky   MeSH
• gonorea farmakoterapie   MeSH
• injekce intramuskulární MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• rektum mikrobiologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin MeSH
• ceftriaxon MeSH
• gentamiciny MeSH

Primary ciliary dyskinesia (PCD) is a genetic disorder associated with recurrent and chronic respiratory infections due to functional defects of motile cilia. In this study, we aimed to elucidate inflammatory and proliferative responses in PCD respiratory epithelium and evaluate the effect of Azithromycin (AZT) on these responses. Airway basal cells (BCs) were isolated from nasal samples of Wild-type (WT) epitope of healthy donors and PCD donors with bi-allelic mutations in DNAH5, DNAH11 and CCDC39. Cells were expanded in vitro and stimulated with either Lipopolysaccharide (LPS) or vehicle control. Post stimulation, cells were treated with either Azithromycin (AZT) or vehicle control. Cell proliferation was imaged in real-time. Separately, BCs from the same donors were expanded and grown at an air-liquid interface (ALI) to generate a multi-ciliated epithelium (MCE). Once fully mature, cells were stimulated with LPS, AZT, LPS + AZT or vehicle control. Inflammatory profiling was performed on collected media by cytokine Luminex assay. At baseline, there was a significantly higher mean production of pro-inflammatory cytokines by CCDC39 BCs and MCEs when compared to WT, DNAH11 and DNAH5 cells. AZT inhibited production of cytokines induced by LPS in PCD cells. Differences in cell proliferation were noted in PCD and this was also corrected with AZT treatment.

• MeSH
• azithromycin * farmakologie   MeSH
• cytokiny MeSH
• epitelové buňky MeSH
• lidé MeSH
• lipopolysacharidy toxicita   MeSH
• poruchy ciliární motility * MeSH
• proliferace buněk MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azithromycin * MeSH
• cytokiny MeSH
• lipopolysacharidy MeSH

• MeSH
• antibakteriální látky MeSH
• azithromycin * MeSH
• frambézie * MeSH
• lidé MeSH
• Treponema pallidum MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin * MeSH

BACKGROUND: Treponema pallidum subspecies pertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed. METHODS: In an open-label, cluster-randomized, community-based trial conducted in a yaws-endemic area of Papua New Guinea, we randomly assigned 38 wards (i.e., clusters) to receive one round of mass administration of azithromycin followed by two rounds of target treatment of active cases (control group) or three rounds of mass administration of azithromycin (experimental group); round 1 was administered at baseline, round 2 at 6 months, and round 3 at 12 months. The coprimary end points were the prevalence of active cases of yaws, confirmed by polymerase-chain-reaction assay, in the entire trial population and the prevalence of latent yaws, confirmed by serologic testing, in a subgroup of asymptomatic children 1 to 15 years of age; prevalences were measured at 18 months, and the between-group differences were calculated. RESULTS: Of the 38 wards, 19 were randomly assigned to the control group (30,438 persons) and 19 to the experimental group (26,238 persons). A total of 24,848 doses of azithromycin were administered in the control group (22,033 were given to the participants at round 1 and 207 and 2608 were given to the participants with yaws-like lesions and their contacts, respectively, at rounds 2 and 3 [combined]), and 59,852 doses were administered in the experimental group. At 18 months, the prevalence of active yaws had decreased from 0.46% (102 of 22,033 persons) at baseline to 0.16% (47 of 29,954 persons) in the control group and from 0.43% (87 of 20,331 persons) at baseline to 0.04% (10 of 25,987 persons) in the experimental group (relative risk adjusted for clustering, 4.08; 95% confidence interval [CI], 1.90 to 8.76). The prevalence of other infectious ulcers decreased to a similar extent in the two treatment groups. The prevalence of latent yaws at 18 months was 6.54% (95% CI, 5.00 to 8.08) among 994 children in the control group and 3.28% (95% CI, 2.14 to 4.42) among 945 children in the experimental group (relative risk adjusted for clustering and age, 2.03; 95% CI, 1.12 to 3.70). Three cases of yaws with resistance to macrolides were found in the experimental group. CONCLUSIONS: The reduction in the community prevalence of yaws was greater with three rounds of mass administration of azithromycin at 6-month intervals than with one round of mass administration of azithromycin followed by two rounds of targeted treatment. Monitoring for the emergence and spread of antimicrobial resistance is needed. (Funded by Fundació "la Caixa" and others; ClinicalTrials.gov number, NCT03490123.).

• MeSH
• antibakteriální látky aplikace a dávkování   MeSH
• azithromycin aplikace a dávkování   MeSH
• bakteriální léková rezistence MeSH
• dítě MeSH
• frambézie farmakoterapie   epidemiologie   MeSH
• Haemophilus ducreyi izolace a purifikace   MeSH
• kojenec MeSH
• kožní vředy mikrobiologie   MeSH
• lidé MeSH
• masová profylaxe * MeSH
• mladiství MeSH
• polymerázová řetězová reakce MeSH
• předškolní dítě MeSH
• prevalence MeSH
• Treponema izolace a purifikace   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Papua Nová Guinea epidemiologie   MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin MeSH

• MeSH
• antibakteriální látky MeSH
• azithromycin * MeSH
• ceftriaxon MeSH
• gentamiciny MeSH
• gonorea * MeSH
• lidé MeSH
• Neisseria gonorrhoeae MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin * MeSH
• ceftriaxon MeSH
• gentamiciny MeSH

Although Chlamydia trachomatis resistance is not of great concern due to its excellent sensitivity to the currently recommended first-line antibiotics (azithromycin and doxycycline), clinical treatment failures have been reported and some of them were linked to laboratory proved resistance. The aim of this study was to determine in vitro susceptibility to azithromycin and doxycycline for 24 urogenital chlamydial strains isolated in Croatia-a country with the highest consumption of azithromycin in Europe and with very high antibiotic prescription rates. Fourteen isolates from cervical swabs, nine from male urethral swabs, and one isolate from expressed prostatic secretion were tested in McCoy cell culture system. All strains were susceptible to azithromycin and doxycycline with minimal inhibitory concentration for azithromycin and doxycycline ranging from 0.064 to 0.125 μg/mL and 0.016 to 0.064 μg/mL, and minimal chlamydicidal concentration ranging from 0.064 to 2.0 μg/mL and 0.032 to 1.0 μg/mL, respectively. Since we still lack information on whether C. trachomatis is evolving in vivo in response to antibiotic selection pressure, this kind of surveillance for resistance is essential in detecting shifts in antimicrobial susceptibilities.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• azithromycin farmakologie   terapeutické užití   MeSH
• Chlamydia trachomatis účinky léků   izolace a purifikace   MeSH
• chlamydiové infekce mikrobiologie   MeSH
• doxycyklin farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mužské urogenitální nemoci mikrobiologie   MeSH
• spotřeba léčiv MeSH
• ženské urogenitální nemoci mikrobiologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Chorvatsko MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin MeSH
• doxycyklin MeSH

OBJECTIVES: To characterize the genetic basis of azithromycin resistance in Escherichia coli and Salmonella collected within the EU harmonized antimicrobial resistance (AMR) surveillance programme in 2014-18 and the Danish AMR surveillance programme in 2016-19. METHODS: WGS data of 1007 E. coli [165 azithromycin resistant (MIC > 16 mg/L)] and 269 Salmonella [29 azithromycin resistant (MIC > 16 mg/L)] were screened for acquired macrolide resistance genes and mutations in rplDV, 23S rRNA and acrB genes using ResFinder v4.0, AMRFinder Plus and custom scripts. Genotype-phenotype concordance was determined for all isolates. Transferability of mef(C)-mph(G)-carrying plasmids was assessed by conjugation experiments. RESULTS: mph(A), mph(B), mef(B), erm(B) and mef(C)-mph(G) were detected in E. coli and Salmonella, whereas erm(C), erm(42), ere(A) and mph(E)-msr(E) were detected in E. coli only. The presence of macrolide resistance genes, alone or in combination, was concordant with the azithromycin-resistant phenotype in 69% of isolates. Distinct mph(A) operon structures were observed in azithromycin-susceptible (n = 50) and -resistant (n = 136) isolates. mef(C)-mph(G) were detected in porcine and bovine E. coli and in porcine Salmonella enterica serovar Derby and Salmonella enterica 1,4, [5],12:i:-, flanked downstream by ISCR2 or TnAs1 and associated with IncIγ and IncFII plasmids. CONCLUSIONS: Diverse azithromycin resistance genes were detected in E. coli and Salmonella from food-producing animals and meat in Europe. Azithromycin resistance genes mef(C)-mph(G) and erm(42) appear to be emerging primarily in porcine E. coli isolates. The identification of distinct mph(A) operon structures in susceptible and resistant isolates increases the predictive power of WGS-based methods for in silico detection of azithromycin resistance in Enterobacterales.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• azithromycin * farmakologie   MeSH
• bakteriální geny MeSH
• bakteriální léková rezistence * genetika   MeSH
• epidemiologické monitorování MeSH
• Escherichia coli * účinky léků   genetika   MeSH
• genotyp MeSH
• infekce vyvolané Escherichia coli mikrobiologie   MeSH
• makrolidy farmakologie   MeSH
• maso * mikrobiologie   MeSH
• mikrobiální testy citlivosti * MeSH
• plazmidy genetika   MeSH
• prasata MeSH
• Salmonella * účinky léků   genetika   izolace a purifikace   MeSH
• sekvenování celého genomu MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antibakteriální látky * MeSH
• azithromycin * MeSH
• makrolidy MeSH

A validated, highly sensitive, and selective HPLC method with MS-MS detection has been developed for quantitative determination of azithromycin (AZI) in human Na2EDTA plasma. Roxithromycin (ROX) was used as internal standard. Human plasma containing AZI and internal standard was ultrafiltered through Centrifree Micropartition devices and the concentration of AZI was determined by isocratic HPLC-MS-MS. Multiple reaction monitoring mode (MRM) was used for MS-MS detection. The calibration plot was linear in the concentration range 2.55-551.43 ng mL(-1). Inter-day and Intra-day precision and accuracy of the proposed method were characterized by R.S.D and percentage deviation, respectively; both were less than 8%. Limit of quantification was 2.55 ng mL(-1). The proposed method was used to determine the pharmacokinetic profile of AZI (250-mg tablets).

• MeSH
• antibakteriální látky krev   chemie   MeSH
• azithromycin krev   MeSH
• časové faktory MeSH
• EDTA krev   MeSH
• hmotnostní spektrometrie metody   MeSH
• lidé MeSH
• referenční hodnoty MeSH
• reprodukovatelnost výsledků MeSH
• roxithromycin chemie   MeSH
• senzitivita a specificita MeSH
• ultrafiltrace MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• validační studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin MeSH
• EDTA MeSH
• roxithromycin MeSH

BACKGROUND: Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection. METHODS: Design: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult (> 18 years) within 24 h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for ≥ 1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy. INTERVENTIONS: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800 mg orally in two doses followed by 400 mg daily in two doses and azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. SECONDARY OUTCOMES: The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90. DISCUSSION: Although both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival. TRIAL REGISTRATION: Clinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).

• Klíčová slova
• Azithromycin, COVID-19, Hydroxychloroquine, Novel coronavirus, Respiratory failure, SARS-CoV-2,
• MeSH
• azithromycin aplikace a dávkování   MeSH
• Betacoronavirus * MeSH
• COVID-19 MeSH
• dvojitá slepá metoda MeSH
• hydroxychlorochin aplikace a dávkování   MeSH
• jednotky intenzivní péče MeSH
• kombinovaná farmakoterapie MeSH
• koronavirové infekce farmakoterapie   mortalita   MeSH
• lidé MeSH
• pandemie MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma * MeSH
• SARS-CoV-2 MeSH
• virová pneumonie farmakoterapie   mortalita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• protokol klinické studie MeSH
• Názvy látek
• azithromycin MeSH
• hydroxychlorochin MeSH

OBJECTIVE: The aim of the study was to determine trends in the minimum inhibitory concentrations (MICs) of erythromycin used as first-line therapy and alternative antibiotics against Bordetella pertussis (B. pertussis) strains isolated from patients with whooping cough in the Czech Republic (CR) in three periods from 1967 to 2015. METHODS: In total, 135 isolates from the years 1967–2015 were analysed. The strains were divided into three groups by the year of isolation: 1967–1999 (42 strains), 2004–2010 (43 strains), and 2011–2015 (50 strains). MIC of selected antibiotics (erythromycin, clarithromycin, azithromycin, ciprofloxacin, and trimethoprim/sulfamethoxazole) were obtained by the reference agar dilution method on Bordet Gengou Agar with 15% defibrinated sheep blood. RESULTS: The study set included 70 strains previously tested for MICs of erythromycin and four other antibiotics. In the three study periods, the MICs of the tested antibiotics for B. pertussis were nearly identical. All but a single strain, inhibited by erythromycin at a concentration of 0.03 mg/l, were inhibited by two concentrations of erythromycin and azithromycin (0.06 and 0.125 mg/l). Clarithromycin inhibited the strains from all three study periods at the following concentrations: 0.03, 0.06, and 0.125 mg/l. Any of the 135 strains was inhibited by ciprofloxacin at a single concentration of 0.06 mg/l and by trimethoprim/sulfamethoxazole at three concentrations (0.125, 0.25, and 0.5 mg/l). CONCLUSION: The study set of 135 Czech strains of B. pertussis isolated in 1967–2015 appears to be homogeneous in terms of the MICs for five antimicrobials. The MICs remained in a narrow range of two to three low concentrations; the unimodal distribution of the MICs suggests the absence of resistance mechanisms. The highest MICs of erythromycin, clarithromycin, and azithromycin were equally 0.125 mg/l, that of ciprofloxacin was 0.06 mg/l, and that of trimethoprim/sulfamethoxazole was 0.5 mg/l. Over the study period of 55 years, the MICs of the study antibiotics remained in the same ranges.

• Klíčová slova
• Bordetella pertussis, MIC, erythromycin, clarithromycin, azithromycin, ciprofloxacin, trimethoprim/sulfamethoxazole,
• MeSH
• antibakteriální látky farmakologie   MeSH
• azithromycin farmakologie   MeSH
• Bordetella pertussis účinky léků   MeSH
• ciprofloxacin farmakologie   MeSH
• dítě MeSH
• dospělí MeSH
• erythromycin farmakologie   MeSH
• klarithromycin farmakologie   MeSH
• kojenec MeSH
• kombinace léků trimethoprim a sulfamethoxazol farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti metody   statistika a číselné údaje   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pertuse farmakoterapie   MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin MeSH
• ciprofloxacin MeSH
• erythromycin MeSH
• klarithromycin MeSH
• kombinace léků trimethoprim a sulfamethoxazol MeSH