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BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is associated with significant morbidity and mortality. Immune dysregulation is a hallmark of sepsis, with important contributions to organ dysfunction including injury and repair mechanisms in AKI. Macrolide antibiotics, such as azithromycin, have previously demonstrated in pre-clinical models a myriad of immunomodulatory effects that may benefit critically ill patients with SA-AKI. The aim of this study was to determine if early receipt of azithromycin in SA-AKI is associated with a reduction in major adverse kidney events (MAKE) at hospital discharge. METHODS: This was a single center, retrospective cohort study of critically ill adult patients with SA-AKI. Early exposure to azithromycin was defined as receipt of one or more doses within 48 hours of a hospital admission with SA-AKI. The primary outcome of MAKE assessed at hospital discharge was the composite of death, requirement for kidney replacement therapy, or a decline in estimated glomerular filtration rate of 25% or more. Multivariable logistic regression was used to account for potential confounders in the assessment. RESULTS: Of 737 included patients with SA-AKI, 152 (20.6%) received azithromycin. Patients that received early azithromycin were less likely to experience MAKE at hospital discharge when compared to those patients not receiving azithromycin: 38.8% versus 48.4% (p=0.035). In multivariable logistic regression, receipt of azithromycin was independently associated with a decreased odds of MAKE at hospital discharge (aOR 0.62, 95% CI 0.41–0.93). CONCLUSIONS: Early exposure to azithromycin in SA-AKI is independently associated with lower odds of MAKE at hospital discharge.

Background and objective Low-dose long-term azithromycin is recommended in clinical practice guidelines for obstructive airway diseases (OADs), however, an optimal therapeutic regimen is not yet established. This study aimed to understand the patterns of azithromycin use in OADs, characterise the patients who received it, and evaluate its safety and efficacy using real-world data. METHODS: We audited 91 patients who had received azithromycin for at least 4 weeks for the management of asthma, chronic obstructive pulmonary disease (COPD) or non-cystic fibrosis bronchiectasis. RESULTS: The mean age was 65±18 years, 60% were female, and 48% were ex-smokers. The majority had asthma (75%) either alone (50%) or in combination with COPD (12%) or bronchiectasis (13%). Most (64%) reported cough or sputum at baseline. The most common treatment regimen was azithromycin 250mg daily (73%) for more than 1 year (57%), with only seven adverse events. There was a significant reduction in the proportions of patients requiring emergency department visits (48% versus 32%; p

Introducción. Muchos antivirales, como hidroxicloroquina, se han utilizado para el tratamiento de COVID-19. La prolongación del QTc es un efecto adverso preocupante, escasamente estudiado en pediatría. Pacientes y métodos. Los pacientes pediátricos con COVID-19 que recibieron tratamiento antiviral se emparejaron (1:2) con controles no infectados ni expuestos al tratamiento. Se analizaron prospectivamente los electrocardiogramas basal, en las primeras 72 horas de tratamiento y posterior a 72 horas. Resultados. Once (22,9%) de 48 pacientes pediátricos ingresados por COVID-19 (Marzo-Julio 2020) recibieron terapia antiviral. Todos presentaban patologías de base; destacando cardiopatías (4/11; 36,4%) e inmunosupresión (3/11; 27,3%); 5/11 (45,5%) recibían tratamiento de base con potencial efecto sobre el QTc. No hubo diferencias en el QTc basal entre casos y controles: 414,8ms (49,2) vs 416,5ms (29,4) (p=0,716). Se observó QTc prolongado basal en 2/11 casos y 2/22 controles. De los casos, 10/11 (90,9%) recibieron hidroxicloroquina, principalmente asociada a azitromicina (8/11; 72,7%); tres recibieron lopinavir/ritonavir, uno remdesivir. La mediana de incremento del QTc tras 72 horas fue de 28,9ms [RIC 48,7] (p=0,062); 4/11 (36,4%) presentaron un QTc largo, de los cuáles en tres ≥500ms. En uno se paró el tratamiento (QTc 510ms) pero no se documentaron arritmias ventriculares. Conclusiones. El uso de fármacos antivirales causó un incremento del QTc tras 72 horas de tratamiento, considerándose un QTc largo en el 36,4% de los pacientes, aunque no se objetivaron eventos arrítmicos. El uso de hidroxicloroquina y antivirales requiere monitorización activa del QTc y se recomienda suspender el tratamiento si el QTc >500ms.

While looking for a “magic bullet” to treat COVID-19, the massive off-label use of several of drugs in COVID-19, including repurposed antimalarial drugs, immunosuppressive agents, anti-virals and antibacterial agents, have generated concerns in the early phase of the pandemic due a possible arrhythmogenic effects in relation to QTc interval prolongation. Indeed, some of these drugs have been historically associated to QT prolongation and Torsade de Point, a potentially lethal ventricular arrhythmia, and their first-time use on a very large scale has raised several concerns in the scientific community. The aim of this work is to summarize the underlying arrhythmogenic mechanisms related to the use of potentially QT prolonging drugs used during the pandemic to treat COVID-19.

This study aimed to characterize adverse drug reactions (ADRs) to hydroxychloroquine in the setting of Covid-19, occurring in Italy in the period March-May 2020. The analysis of the combination therapy with azithromycin or/and lopinavir/ritonavir as well as a comparison with ADRs reported throughout 2019 was performed. ADRs collected by the Italian National Network of Pharmacovigilance were analysed for their incidence, seriousness, outcome, co-administered drugs, MedDRA classification. 306 reports were gathered for the quarter of 2020: 54 % non-serious and 46 % serious, and half of the latter required either the hospitalisation or its prolongation. However most of them were either completely recovered (26 %) or in the process of recovery (45 %), except for 9 fatal cases. Throughout 2019, 38 reports were collected, 53 % non-serious and 47 % serious, but no death had been reported. Diarrhea, prolonged QT interval and hypertransaminasemia were the most frequently ADRs reported in 2020, significantly higher than 2019 and specific for COVID-19 subjects treated with hydroxychloroquine. The logistic regression analyses demonstrated that the likelihood of serious ADR, QT prolongation and diarrhea significantly increased with hydroxychloroquine dosage. Co-administration of lopinavir/ritonavir and hydroxychloroquine showed a positive correlation with diarrhea and hypertransaminasemia and a negative relationship with the ADR seriousness. The combination therapy with azithromycin was another independent predictor of a serious ADR. Off-label use of hydroxychloroquine for COVID-19, alone or in combination regimens, was associated with increased incidence and/or seriousness of specific ADRs in patients with additional risk factors caused by the infection. This article is protected by copyright. All rights reserved.

Infants ages < 6 months do not receive azithromycin as part of trachoma control and thus may serve as an infection reservoir in persistently endemic districts. The aim of this study was to determine the population-based Chlamydia trachomatis infection prevalence and infectious load among infants ages 1–12 months in persistently trachoma endemic districts in Amhara, Ethiopia. Across six districts, 475 infants were enumerated, and of these 464 (97.7%) were swabbed for infection testing. The C. trachomatis infection prevalence in the study area among infants was 0.2% (95% CI: 0.0–1.5). Among children ages 0–5 years positive for C. trachomatis, the median load was 31 elementary bodies (EB) (Inter quartile range: 7–244 EB), and the infection-positive infant had a load of 7,755 EB. While it is worth reconsidering azithromycin treatment recommendations for the potential mortality benefits, these results do not support lowering the treatment age for trachoma control.

The aim of this study was to characterize the evolution of gonorrhea in the general population by correlating epidemiological, genotypic, and antimicrobial resistance data of Neisseria gonorrhoeae ...

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 μg/ml (2 μg/ml), 1 μg/ml (0.5 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.125 μg/ml (0.063 μg/ml), 0.125 μg/ml (0.125 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.031 μg/ml (0.031 μg/ml), 0.25 μg/ml (0.125 μg/ml), and 0.016 μg/ml (0.008 μg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth.

The aim of this short communication is to describe a case of subfertility and other anomalies associated with the presence of Mycoplasma spumans and Mycoplasma maculosum in a Bernese Mountain Dog kennel. After the arrival of two dogs from abroad, some fertility disorders, such as unsuccessful mating, pregnancy losses and abnormal sperm analysis results, were observed. Two consecutive samplings (vaginal swabs) of three and two bitches with problems, respectively, were performed and M. spumans and M. maculosum were identified by PCR and sequencing. After treatment for 15 days with doxycycline and 9 days with azithromycin, successful pregnancies were achieved and the results of the sperm analyses were reversed. Considering that no other infectious agents causing subfertility problems were detected and that no management measures or other medication apart from these antibiotics were applied, it was concluded that fertility problems were due to the presence of these two Mycoplasma species.

Cystic fibrosis (CF) is a serious lung disease, commonly susceptible to Pseudomonas aeruginosa colonization. The dense mucus together with biofilm formation limit drug permeability and prevent the drug from reaching the site of action, causing treatment failure of the bacterial infection. Besides the use of antibiotics, the mucolytic agent N-acetylcysteine (NAC) is recommended to be co-administered in the treatment of CF. Although several formulations have been developed for inhalation therapy to improve the pulmonary condition in CF patients, there is still no comprehensive study on a combined multifunctional dry powder formulation of antibiotics with NAC. In this work, we developed an innovative multifunctional dry powder inhaler (DPI) formulation based on salt formation between NAC and antibiotics and characterized their solid state properties and physical stability. NAC could be spray dried together with three different antibiotics, azithromycin (Azi), tobramycin (Tobra) and ciprofloxacin (Cipro), without the use of organic solvents to form Azi/NAC, Tobra/NAC and Cipro/NAC DPI formulations. Solid-state characterization of these DPI formulations showed that they were amorphous after spray drying. Azi/NAC and Tobra/NAC form co-amorphous salt systems that were physically stable under storage at stress conditions. For particle characterization, the obtained mass median aerodynamic diameters were in a suitable range for inhalation (< 5.0μm). The multifunctional antibiotic/NAC formulations conserved or improved the antibiotic susceptibility and showed promising results regarding the inhibition of P. aeruginosa PA14 biofilm formation.

Pheretima posthuma (Vaillant, 1868), a native earthworm of Pakistan and Southeast Asia, has wide utilization in vermicomposting and bioremediation process. In this study, P. posthuma coelomic fluid (PCF) and body paste (PBP) was evaluated as antibacterial agent against ampicillin (AMP) resistant five Gram positive and four Gram negative clinical isolates. The antibacterial effect of different doses (i.e. 25-100 µg/ml) of PCF and PBP along with AMP and azithromycin (AZM) (negative and positive controls, respectively) were observed through disc diffusion and micro-dilution methods. All nine clinical isolates were noticed as AMP resistant and AZM sensitive. Antibacterial effects of PCF and PBP were dose dependent and zone of inhibitions (ZI) against all clinical isolates were between 23.4 ± 0.92 to 0 ± 00 mm. The sensitivity profile of PCF and PBP against clinical isolates was noticed as 44.44 and 55.56%, respectively. Both PCF and PBP showed bacteriostatic (BTS) action against S. aureus, S. pyogenes, K. pneumonia, N. gonorrhoeae. Moreover, the cumulative BTS potential of PCF and PBP against all isolates was 66.67 and 55.56%, respectively. The MICs of PCF and PBP were ranged from 50-200 µg/ml against selected isolates. The bacterial growth curves indicated that PCF and PBP inhibited the growth of all isolates at their specific MIC concentrations. However, PBP has better antibacterial potential compared to PCF against selected isolates. Therefore, it is concluded that both PCF and PBP of P. posthuma possess antibacterial and BTS potential against ampicillin resistant clinical isolates. This organism might be considered as a second choice of antibacterial agents and can further be utilized in pharmaceutical industries for novel drug manufacturing by prospecting bioactive potential agents. Resumo Pheretima posthuma (Vaillant, 1868), uma minhoca nativa do Paquistão e sudeste da Ásia, tem ampla utilização em processos de vermicompostagem e biorremediação. Neste estudo, o fluido celômico de P. posthuma (PCF) e a pasta corporal (PBP) foram avaliados como agente antibacteriano contra cinco isolados clínicos Gram-positivos e quatro Gram-negativos resistentes à ampicilina (AMP). O efeito antibacteriano de diferentes doses (ou seja, 25-100 µg / ml) de PCF e PBP juntamente com AMP e azitromicina (AZM) (controles negativo e positivo, respectivamente) foi observado por meio de métodos de difusão em disco e microdiluição. Todos os nove isolados clínicos foram notados como resistentes a AMP e sensíveis a AZM. Os efeitos antibacterianos de PCF e PBP foram dependentes da dose e a zona de inibição (ZI) contra todos os isolados clínicos foi entre 23,4 ± 0,92 a 0 ± 00 mm. O perfil de sensibilidade do PCF e PBP contra isolados clínicos foi observado como 44,44% e 55,56%, respectivamente. Tanto o PCF quanto o PBP mostraram ação bacteriostática (BTS) contra S. aureus, S. pyogenes, K. pneumonia, N. gonorrhoeae. Além disso, o potencial BTS cumulativo de PCF e PBP contra todos os isolados foi de 66,67% e 55,56%, respectivamente. Os MICs de PCF e PBP variaram de 50-200 µg / ml contra isolados selecionados. As curvas de crescimento bacteriano indicaram que o PCF e o PBP inibiram o crescimento de todos os isolados em suas concentrações específicas de MIC. No entanto, PBP tem melhor potencial antibacteriano em comparação com PCF contra isolados selecionados. Portanto, conclui-se que tanto o PCF quanto o PBP de P. posthuma possuem potencial antibacteriano e BTS contra isolados clínicos resistentes à ampicilina. Esse organismo pode ser considerado como uma segunda escolha de agentes antibacterianos e pode ainda ser utilizado nas indústrias farmacêuticas para a fabricação de novos medicamentos por meio da prospecção de agentes com potencial bioativo.

A four-year-old intact male Boxer, that had a history of travelling to Serbia, was referred for lethargy and anaemia. Shortly before the dog was referred, it was diagnosed twice with an infection with Babesia canis and was treated with imidocarb both times. A blood smear evaluation was indicative of the presence of intraerythrocytic piroplasms. After receiving inconclusive results regarding the type of piroplasm, the dog was diagnosed with simultaneous infections with B. canis and Babesia gibsoni via real-time polymerase chain reaction (rt-PCR) testing. The dog was treated with imidocarb, atovaquone and azithromycin, and in a follow-up examination, the PCR results were negative for B. canis and B. gibsoni. Several weeks later, the dog was presented again, and a PCR was positive for B. gibsoni. After atovaquone and azithromycin failed to eliminate the parasites, a therapy attempt using metronidazole, clindamycin and doxycycline was initiated. Six months after diagnosis, the treatment appeared successful in eliminating B. gibsoni. This case report describes the clinical findings of the co-infection and the initiated diagnostic and therapeutic approaches.

Azithromycin is an antibiotic listed in the essential list of medicines for adults and pediatrics. Conflicting evidence has been found regarding azithromycin classification according to the Biopharmaceutics classification system (BCS). The purpose of this study was to identify the critical variables that influence the oral absorption of azithromycin in adults and pediatrics.Azithromycin solubility and dissolution studies (oral suspension) were performed in buffers and biorelevant media simulating the fasted and fed gastrointestinal tract. A PBPK model was developed for azithromycin for healthy adult volunteers and pediatrics (Simcyp® v18.2) informed by in vitro solubility and dissolution studies to predict drug performance after administration of azithromycin as an oral suspension.The developed PBPK model predicted azithromycin plasma concentrations-time profiles after administration of an oral suspension to adults and pediatrics. Sensitivity analysis of solubility vs dose suggests that absorption is independent of solubility within the therapeutic dose range in both adults and pediatrics. The developed PBPK model for adults and pediatrics was consistent with the mechanism of permeation through the intestinal membrane (passive and active processes) being the rate-limiting step of azithromycin's absorption.The physiologically based approach proposed was shown to be useful to determine the factors controlling drug absorption in adults and pediatrics.

Background. Antimicrobial resistance is one of the most crucial problems in human health care worldwide. The main cause of this crisis is the excessive and misuse of antibacterial drugs (ADs). The highest rate of improper antibiotics' prescriptions in pediatric practice is observed at treatment of respiratory tract infections in outpatient clinics.Objective. The aim of the study is to analyze the clinical practice of management of patients with acute respiratory infections (ARI) and the use of ADs in children's outpatient clinics across the regions of Russian Federation.Methods. Multicenter retrospective study was conducted. All ARI cases documented in 969 medical records (form 112/y) of children born in 2015–2017 yy. in 16 regions of Russian Federation (selected randomly) were analyzed.Results. Acute viral infection was diagnosed in 79.6% cases of referencing to doctor with ARI symptoms. Systemic ADs were prescribed in 23% cases of ARI. Antibacterial therapy was received by 14% of children diagnosed with acute respiratory viral infection, 35% with acute laryngotracheitis, 80% with acute bronchitis, 76% with acute rhinosinusitis, 94% with ARI associated with otitis media, 52% with tonsillopharyngitis, and 100% with community-acquired pneumonia. Amoxicillin (35%), amoxicillin/clavulanic acid (24%), azithromycin (20.2%) were prescribed most often. Parenteral administration of ADs was prescribed in 3.9% of cases, mostly for children with community-acquired pneumonia. Prescribed antibacterial therapy was unreasonable in 84% of analyzed cases. Polypragmasy occurred in 50.5% of cases. Clinical protocols violations were mostly common for management of patients with laryngotracheitis and tonsillopharyngitis.Conclusion. There is favorable trend towards the decrease in ADs prescribing frequency in outpatient clinics for children with ARI. Thus, polypragmasy and irrational choice of antibacterial therapy frequency remains quite high.

Backgrounds:. Azithromycin mass drug administration (MDA) is a key part of the strategy for controlling trachoma. This systematic review aimed to comprehensively summarize the present studies of azithromycin MDA on trachoma; provide an overview of the impact of azithromycin MDA on trachoma in different districts; and explore the possible methods to enhance the effectiveness of azithromycin MDA in hyperendemic districts. Methods:. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched up to February 2021 with no language restriction. Studies reporting the effect of azithromycin MDA on trachoma were included. Mathematical modeling studies, animal studies, case reports, and reviews were excluded. The trachomatous inflammation-follicular (TF) 30.0%), especially with baseline TF >50.0%, annual MDA was unable to achieve the TF 10.0% is not appropriate for all eligible districts.

Background: Group A Streptococcus (GAS) is an important pathogen causing morbidity and mortality worldwide. Surveillance of resistance and emm type has important implication to provide helpful information on the changing GAS epidemiology and empirical treatment. Methods: To study the emergence of resistant GAS in children with upper respiratory tract infection (URTI), a retrospective study was conducted from 2000 to 2019 in southern Taiwan. Microbiological studies, including antibiotic susceptibility, were performed. GAS emm types and sequences were determined by molecular methods. The population was divided into two separate decades to analyze potential changes over time. The 1st decade was 2000–2009; the 2nd decade was 2010–2019. Multivariate analyses were performed to identify independent risk factors associated with macrolide resistance between these periods. Results: A total of 320 GAS from 339 children were enrolled. Most of the children (75%) were under 9 years of age. The most common diagnosis was scarlet fever (225, 66.4%), and the frequency increased from 54.8% in the 1st to 77.9% in the 2nd decade (p

Introduction: Data about consumption of antibiotics in Spain are worrisome. They are mainly prescribed in the community sector and there is a high exposure to antibiotics in the pediatric population. The aim of this study is to describe the evolution of antibiotic consumption in the pediatric population of Asturias during 2005–2018 period. Methods: Retrospective and descriptive study using data about consumption of antibacterial agents for systemic use (J01 group of the Anatomical Therapeutic Chemical Classification) in pediatric outpatients in Asturias between 2005 and 2018. Data, expressed as defined daily dose (DDD) per 1000 inhabitants per day (DID), in three periods were compared. Results: Mean antibiotic consumption in pediatric outpatients in Asturias (2005–2018) was 14 DID (CI95% 13.4–14.6). Consumption increased until 2009 (15.2 DID) and decreased from 2015 onwards (11.9 DID in 2018). Remarkable data along the study were: 1) increase in amoxicillin consumption (p = 0.027), that have exceeded that of amoxicillin-clavulanate since 2011; 2) steady consumption of macrolides, with an increase in azithromycin (p

Objective With the ongoing COVID-19 pandemic, large numbers of people will receive one of the several medications proposed to treat COVID-19, including patients of reproductive age. Given that some medications have shown adverse effects on sperm quality, there might be a transgenerational concern. We aim at examining the association between drugs proposed to treat COVID-19 when taken by the father around conception and any pre-term birth or major birth defects in offspring in a nation-wide cohort study using Danish registry data. Offspring whose father filled at least one prescription of the following medications in the 3 months preceding conception were considered exposed: chloroquine, hydroxychloroquine, losartan, azithromycin, naproxen, dexamethasone and prednisone. Results For azithromycin and naproxen, large numbers of offspring were exposed (> 1800 offspring), and we found no association with adverse birth outcomes. For chloroquine, losartan and dexamethasone, exposure was intermediate (~ 900 offspring), and there was no statistically significant association with birth defects. For hydroxychloroquine and prednisone, exposure was limited (

BackgroundLow-dose oral azithromycin therapy is recommended as a preventive treatment for acute exacerbations of COPD. However, the overall benefit–harm balance of this treatment has not been well studied.MethodsA probabilistic Markov model of COPD was created to simulate the course of COPD over 20 years. The model was populated with evidence from the literature and dedicated data analysis. The benefit of azithromycin was modelled as a reduction in exacerbation rates. Adverse events, including cardiovascular events, hearing loss, gastrointestinal symptoms and antimicrobial resistance (leading to a gradual decline in the effectiveness of azithromycin), were considered. All outcomes were assigned a health-related utility weight to estimate the overall net change in the quality-adjusted life year (QALY) associated with the use of azithromycin.ResultsIn patients with a positive exacerbation history, azithromycin resulted in a net QALY gain of 17.9 per 100 patients (99.8% probability of expected QALY gain) over 20 years. The net benefit increased to 21.8 QALYs per 100 patients (99.9% probability of expected QALY gain) among the ‘frequent exacerbator’ subgroup. Azithromycin was not net beneficial among those without any moderate/severe exacerbations in the previous year. Findings were robust against series of sensitivity, scenario and threshold analyses.ConclusionsLong-term therapy with azithromycin confers a net benefit to ex-smoker patients with COPD with a recent history of exacerbations and an even larger benefit to those who are frequent exacerbators.

Background. Use of Hydroxychloroquine with or without Azithromycin is repurposed in SARS-CoV-2 in the absence of definitive treatment. Objective. To evaluate the association between the use of Hydroxychloroquine and Azithromycin when given alone or in combination on clinical outcomes and adverse drug reactions among lab confirmed SARS CoV-2 positive patients admitted in a COVID tertiary care hospital of a University Medical college. Methods. a retrospective observational comparative study was conducted. COVID-19 positive patients admitted in study hospital for management of COVID-19 were enrolled into the study. The patients were categorized into 4 treatment groups based on having received the following treatment during hospitalization: (A) Hydroxychloroquine with Azithromycin, (B) Hydroxychloroquine without Azithromycin (Hydroxychloroquine alone), (C) Azithromycin alone, and (D) Neither drug, defined as no receipt of either Hydroxychloroquine or Azithromycin in the record; other medications may have been dispensed. Results. 800 patients were enrolled. Mean±Standard deviation of duration of hospital stay (in days) for study Group A was 11.37±7.11, for Group B was 8.37±4.77, for Group C was 18.22 ± 5.69 and for Group D was 6.12±2.97. Mortality in Group A was 29.74%, Group B – 33.16%, Group C – 0% and in Group D – 1.32%. Conclusion. Among hospitalized patients with COVID-19 treatment, Group C was associated with good clinical outcome. However, the interpretation of these findings may be limited by the observational design.

There are reports of high rates of antibiotic prescribing among hospitalized patients with COVID-19 around the world. To date, however, there are few reports of prescribing in relation to COVID-19 in Pakistan. Herein, we describe a point prevalence survey of antibiotic prescribing amongst patients hospitalized with suspected or proven COVID-19 in Pakistan. A Point Prevalence Survey (PPS) was undertaken in seven tertiary care health facilities in Punjab Provence, Pakistan. Baseline information about antimicrobial use according to the World Health Organization (WHO) standardized methodology was collected on a single day between 5(th) and 30 April 2021. A total of 617 patients’ records were reviewed and 578 (97.3%) were documented to be receiving an antibiotic on the day of the survey. The majority (84.9%) were COVID-19 PCR positive, 61.1% were male and 34.9% were age 36 to 44 years. One quarter presented with severe disease, and cardiovascular disease was the major comorbidity in 13%. Secondary bacterial infection or co-infection (bacterial infection concurrent with COVID-19) was identified in only 1.4%. On the day of the survey, a mean of 1.7 antibiotics was prescribed per patient and 85.4% antibiotics were recorded as being prescribed for ‘prophylaxis’. The most frequently prescribed antibiotics were azithromycin (35.6%), ceftriaxone (32.9%) and meropenem (7.6%). The majority (96.3%) of the antibiotics were empirical and all were from WHO Watch or Reserve categories. Overall, a very high consumption of antibiotics in patients hospitalized with suspected or proven COVID-19 was observed in Pakistan and this is concerning in view of already high rates of antimicrobial resistance in the region. Antimicrobial stewardship programs need to urgently address unnecessary prescribing in the context of COVID-19 infection.

Background Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. Methods Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), one week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin, disc diffusion for tetracycline susceptibility and whole genome sequencing (WGS) to verify/refute treatment failure. Results Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. 141 baseline isolates were tested for gentamicin susceptibility using Etest; 2 (1.4%) MIC = 2 μg/mL; 111 (78.7%) MIC = 4 μg/mL; and 28 (19.9%) MIC = 8 μg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin while 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 μg/mL. Ten men had pre- and post-treatment isolates examined by WGS, 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms (SNPs)), while 8 (80%) were confirmed treatment failures (0-1 SNP). Conclusions Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment for gonorrhea in Malawi should be reassessed.

Background Chlamydia trachomatis (chlamydia) is highly prevalent and is an important sexually transmitted infection as it can lead to increased risk of HIV seroconversion; and if left untreated, can cause infertility in women. Clinical guidelines recommend treating chlamydia presumptively when presenting symptomatically; however, clinicians are now questioning this due to increasing prevalence of antimicrobial resistance. Methods To determine the accuracy of presumptive chlamydia treatment practices at a walk-in sexual health service in regional Australia, we audited all same-day screen and treat presentations prescribed azithromycin over a 6-month period in 2018. Results A total of 325 cases were included in the analysis. Over half (54%) the presentations returned negative pathology for all pathogens investigated. One quarter (25%) of presentations were positive for chlamydia, and (4%) reported a dual infection. A further one fifth (20%) were negative for chlamydia but positive for another pathogen. More symptomatic males than females returned positive pathology for chlamydia (8% vs 4%). Conclusions While presumptive treatment is recommended in the current guidelines, our findings indicate this resulted in over-treatment. Considering the increasing resistance patterns for Mycoplasma genitalium, which include azithromycin, presumptive treatments need to balance immediate client care needs against long-term community antimicrobial resistance outcomes. This internal audit provided a feedback mechanism to the walk-in sexual service, enabling modification of practices to provide more precise, individual clinical care within the bounds of current STI guidelines, while balancing wider the objectives of antimicrobial stewardship.

Objective: The objective of present study was to assess the treatment pattern in the COVID-19 patients. Methods: The present study was a hospital-based prospective observational conducted in Government Medical College Kathua (UT Jammu and Kashmir) on COVID-19 positive confirmed cases from December 2020 to January 2021. Consent was taken from patients who were willing to participate in the study. The details of presenting complaints and treatment received by them and outcome of management was recorded and evaluated from their treatment files. Results: A total 56 patients of COVID-19 were enrolled for the study. Majority of them were males (60.71%) and maximum of the patients between 18 and 60 years constituted 69.6%. COPD (28.5%), severe anemia (21.42%), and diabetes mellitus and hypertension (19.64% each) were common comorbidities. Sore throat, dry cough, and breathlessness were common presenting symptoms. Pattern of antibiotics and antivirals revealed that azithromycin was frequently prescribed (87.5%) followed by hydroxychloroquine (44.64%), linzolid (21.42%), ceftriaxone (19.64%), and remdesivir (14.28%). Majority of patients (>50%) were treated with steroids, while all patients received multivitamins and Vitamin C (100%) and nearly 40% were administered zinc therapy. Conclusions: Azithromycin, hydroxyquinine, remdesivir, and steroids were frequently prescribed in patients of COVID-19. Steroids were administered in oral, inhaler or in injection forms. Multivitamins including Vitamin C were given to all patients. Most of patients had comorbidities including COPD, diabetes mellitus type 2 and severe anemia.

Azithromycin is a macrolide antibiotic. Recent evidence has demonstrated in vitro activity against a wide variety of respiratory tract viruses, including SARS-CoV-2 responsible for the current global pandemic COVID-19. A mechanism of action acting on different phases of the viral cycle is assumed. In addition to its in vitro antiviral properties, some evidence also suggests immunomodulatory and antifibrotic activity. These properties of azithromycin could be useful in the treatment of viral respiratory tract infections such as COVID-19. However, clinical data on the antiviral efficacy of azithromycin in the treatment of respiratory tract infections are inconsistent, both when used as monotherapy and in polypharmacological combination. In addition, cases of azithromycin-induced QT long and malignant arrhythmias are reported. In this short review, we attempt to determine the role of azithromycin in the treatment of viral respiratory tract infections such as COVID-19, therapeutic efficacy, or inefficacy?

Programs to eliminate trachoma as a public health problem use prevalence of the clinical sign trachomatous inflammation—follicular (TF) in 1- to 9-year-olds in endemic districts to make decisions to begin or end mass drug administration with azithromycin. Trachomatous inflammation—follicular is used as a proxy for transmission of ocular Chlamydia trachomatis infection. Long-term monitoring of previously endemic districts for recrudescence of ocular C. trachomatis infection would benefit from a simple blood test that could be integrated with other public health programs. In this study, we evaluated multiple tests to measure antibodies against the C. trachomatis antigen Pgp3—a multiplex bead assay (MBA), an ELISA, and two versions of a lateral flow assay (LFA)—in four districts of the Amhara region of Ethiopia with varying levels of TF. Seroprevalence and seroconversion rate (SCR) results were proportional to TF prevalence by district for most tests, with the notable exception of the LFA using colloidal gold as the developing reagent. Changing the test developing reagent to black latex improved agreement between serological measures and TF prevalence and in inter-rater agreement. Seroconversion rate estimates using data derived from the LFA-gold assay were inconsistent with the shape of the age-seroprevalence curve, which did not increase in older ages. These data revealed potential complications with using SCR that will need further evaluation. Data from MBA, ELISA, and LFA with the black test line showed good agreement with each other and proportionality to TF estimates, providing further data that serology has potential utility for trachoma surveillance.

While facing potentially high morbidity from COVID-19 without known effective therapies, the off-label use of several non-specific drugs has been advocated, including re-purposed anti- viral (e.g., remdesivir or the lopinavir/ritonavir combination), biologic agents (e.g., tocilizumab), and antimalarial drugs such as chloroquine and hydroxychloroquine, in association with or without azithromycin. Data regarding the effectiveness of these drugs in treating COVID-19 has been shown in some trials and clinical settings, but further randomised controlled trials are still being carried out. One of the main concerns regarding their widespread use, however, is their possible effects on the QT interval and arrhythmogenic potential. Some of these drugs have been associated with QT prolongation and Torsades de Point, a potentially lethal ventricular arrhythmia. The review aims to highlight the magnitude of this problem, to quickly refresh clinically impacting cornerstones of QT interval and TdP pathophysiology, to summarize the available evidence regarding the QT and arrhythmia impact of drugs used in different clinical settings in COVID-19 patients, and to help the physicians dealing with the knowledge needed in the everyday clinical duties in case of doubts regarding QT-induced arrhythmias in this time of emergency.

Toussaint Rouamba,1,&ast; Houreratou Barry,2,&ast; Esperance Ouédraogo,1 Marc Christian Tahita,1 Nobila Valentin Yaméogo,3 Armel Poda,4 Arnaud Eric Diendéré,5 Abdoul-Salam Ouedraogo,4 Innocent Valea,1 Amariane M Koné,2 Cherileila Thiombiano,2 Isidore Traoré,2 Zekiba Tarnagda,1 Serge A Sawadogo,6 Zakaria Gansané,7 Yibar Kambiré,8 Idrissa Sanou,8 Fatou Barro-Traoré,8 Maxime K Drabo,1 Halidou Tinto1 On behalf of the CHLORAZ Study Group1Institut de Recherche en Sciences de la Santé (CNRST-IRSS), Nanoro, Burkina Faso; 2Institut National de Santé Publique, Centre Muraz, Bobo-Dioulasso, Burkina Faso; 3Centre Hospitalier Universitaire Yalgado Ouédraogo, Ouagadougou, Burkina Faso; 4Centre Hospitalier Universitaire Sourou Sanon, Bobo-Dioulasso, Burkina Faso; 5Centre Hospitalier Universitaire de Bogodogo, Ouagadougou, Burkina Faso; 6Centre PrïmO Nelson Mandela (Promotion de la Recherche et de l’Innovation en Immunologie Médicale de Ouagadougou), Ouagadougou, Burkina Faso; 7Clinical Monitoring in Africa-Clinical Research Organization, Ouagadougou, Burkina Faso; 8Centre Hospitalier Universitaire de Tengandogo, Ouagadougou, Burkina Faso&ast;These authors contributed equally to this workCorrespondence: Toussaint RouambaInstitut de Recherche en Sciences de la Santé (CNRST-IRSS), 528, Avenue Kumda-Yoore, BP 218 Ouagadougou CMS 11, Ouagadougou, Nanoro, Burkina FasoTel +226 666 532 04Email rouambatoussaint@gmail.comIntroduction: Though chloroquine derivatives are used in the treatment of coronavirus disease 2019 (COVID-19) in many countries worldwide, doubts remain about the safety and efficacy of these drugs, especially in African communities where published data are scarce.Methods: We conducted an observational prospective cohort study from April 24 to September 03, 2020, in Burkina Faso to assess (as primary outcome) the clinical, biological, and cardiac (electrocardiographic) safety of chloroquine or hydroxychloroquine plus azithromycin administered to COVID-19 patients. The main secondary outcomes were all-cause mortality and median time of viral clearance.Results: A total of 153 patients were enrolled and followed for 21 days. Among patients who took at least one dose of chloroquine or hydroxychloroquine (90.1% [138/153]), few clinical adverse events were reported and were mainly rash/pruritus, diarrhea, chest pain, and palpitations. No statistically significant increase in hepatic, renal, and hematological parameters or electrolyte disorders were reported. However, there was a significant increase in the QTc value without exceeding 500ms, especially in those who received chloroquine phosphate. Three adverse events of special interest classified as serious (known from chloroquine derivatives) were recorded namely pruritus, paresthesia, and drowsiness. One case of death occurred. The average onset of SARS-CoV-2 PCR negativity was estimated at 7.0 (95% CI: 5.0– 10.0) days.Conclusion: Hydroxychloroquine appeared to be well tolerated in treated COVID-19 patients in Burkina Faso. In the absence of a robust methodological approach that could generate a high level of scientific evidence, our results could at least contribute to guide health decisions that should be made based on different sources of scientific evidence including those from our study.Keywords: SARS-CoV-2, chloroquine, hydroxychloroquine, azithromycin, safety, virus shedding

Background: Linagliptin is prescribed as a dipeptidyl peptidase-4 (DPP-4) inhibitor. Azithromycin is specified as an antibiotic that binds with 23s rRNA of the 50s ribosomal subunit, obstructing the microbial protein synthesis. Our study focuses on the drug-drug interactions of these drugs. Objective: The purpose of the study is to understand the bioavailability and physicochemical approaches of Linagliptin and Azithromycin interaction mediated through the strength and nature of the complexation. Methods: The in vitro assessment of drug interaction was conducted using Ultraviolet-visible spectroscopy (UV/VIS), Ultra-Performance Liquid Chromatography (UPLC), Fourier transform infrared spectroscopy (FT-IR), and Differential scanning calorimetry (DSC), while the Oral Glucose Tolerance Test (OGTT) was performed for the in vivo assessment of drug interaction in a mouse model. Results: Mild variation in interaction was observed at different pH values at a specific temperature by Job's and Ardon's equations. In UPLC, the drug mixture assessment showed that the area of Linagliptin was 2013793, and the area of Azithromycin was 54631 in 50 mg/l. The height of Linagliptin in the drug mixture was 579234, and that of Azithromycin was 11442. For Azithromycin, the wavelength of 731.02 cm-1, 993.34 cm-1, 1379.10 cm-1, and 1718.58 cm-1 decreased in the mixture. Also, for Linagliptin, the wavelength 1363.67 cm-1, 1473.62 cm-1, and 1718.58 cm-1 decreased in the drug mixture. The melting endotherm was 125.55°C, melting normalized energy was -3.0 W/mg, and 225.75°C with melting normalized energy of -5.5 W/mg of the drug mixture as indicated by DSC. In the OGTT test, the blood glucose level of Linagliptin decreased in the drug mixture by 13.58 % and 57.25%. Conclusion: Hence, the concomitant administration of Linagliptin and Azithromycin simultaneously might reduce the therapeutic effect of the drug complex.

The purpose of this survey is to explore changes in the management of COVID-19 during the first versus the second wave, with particular emphasis on therapies, antibiotic prescriptions, and elderly care. An internet-based questionnaire survey was distributed to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members. Therapeutic approach to patients with mild-to-moderate (PiO2/FiO2 200–350) and severe (PiO2/FiO2

Summary Background Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major health concerns globally. Increased global surveillance of gonococcal AMR is essential. We aimed to describe the 2017–18 data from WHO's global gonococcal AMR surveillance, and to discuss priorities essential for the effective management and control of gonorrhoea. Methods We did a retrospective observational study of the AMR data of gonococcal isolates reported to WHO by 73 countries in 2017–18. WHO recommends that each country collects at least 100 gonococcal isolates per year, and that quantitative methods to determine the minimum inhibitory concentration of antimicrobials, interpreted by internationally standardised resistance breakpoints, are used. Findings In 2017–18, 73 countries provided AMR data for one or more drug. Decreased susceptibility or resistance to ceftriaxone was reported by 21 (31%) of 68 reporting countries and to cefixime by 24 (47%) of 51 reporting countries. Resistance to azithromycin was reported by 51 (84%) of 61 reporting countries and to ciprofloxacin by all 70 (100%) reporting countries. The annual proportion of decreased susceptibility or resistance across countries was 0–21% to ceftriaxone and 0–22% to cefixime, and that of resistance was 0–60% to azithromycin and 0–100% to ciprofloxacin. The number of countries reporting gonococcal AMR and resistant isolates, and the number of examined isolates, have increased since 2015–16. Surveillance remains scarce in central America and the Caribbean and eastern Europe, and in the WHO African, Eastern Mediterranean, and South-East Asian regions. Interpretation In many countries, ciprofloxacin resistance was exceedingly high, azithromycin resistance was increasing, and decreased susceptibility or resistance to ceftriaxone and cefixime continued to emerge. WHO's global surveillance of gonococcal AMR needs to expand internationally to provide imperative data for national and international management guidelines and public health policies. Improved prevention, early diagnosis, treatment of index patients and partners, enhanced surveillance (eg, infection, AMR, treatment failures, and antimicrobial use or misuse), and increased knowledge on antimicrobial selection, stewardship, and pharmacokinetics or pharmacodynamics are essential. The development of rapid, accurate, and affordable point-of-care gonococcal diagnostic tests, new antimicrobials, and gonococcal vaccines is imperative. Funding None.

Summary Background Mass drug administration of azithromycin to children in sub-Saharan Africa has been shown to improve survival in high-mortality settings. The period after hospital discharge is a time of elevated risk unaddressed by current interventions and might provide an opportunity for targeting empirical azithromycin administration. We aimed to assess the efficacy of azithromycin administered at hospital discharge on risk of death and rehospitalisation in Kenyan children younger than 5 years. Methods In this double-blind, placebo-controlled randomised trial, children were randomly assigned (1:1) to receive a 5-day course of azithromycin (oral suspension 10 mg/kg on day 1, followed by 5mg/kg per day on days 2–5) or identically appearing and tasting placebo at discharge from four hospitals in western Kenya. Children were eligible if they were aged 1–59 months at hospital discharge, weighed at least 2 kg, and had been admitted to hospital for any medical reason other than trauma, poisoning, or congenital anomaly. The primary outcome was death or rehospitalisation in the subsequent 6-month period in a modified intention-to-treat population, compared by randomisation group with Cox proportional hazards regression and Kaplan-Meier. Azithromycin resistance in Escherichia coli isolates from a random subset of children was compared by randomisation group with generalised estimating equations. This trial is registered with ClinicalTrials.gov , NCT02414399 . Findings Between June 28, 2016, and Nov 4, 2019, 1400 children were enrolled in the trial at discharge from hospital, with 703 (50·2%) randomly assigned to azithromycin and 697 (49·8%) to placebo. Among the 1398 children included in the modified intention-to-treat analysis (702 in the azithromycin group and 696 in the placebo group), the incidence of death or rehospitalisation was 20·4 per 100 child-years in the azithromycin group and 22·5 per 100 child-years in the placebo group (adjusted hazard ratio 0·91, 95·5% CI 0·64–1·29, p=0·58). Azithromycin resistance was common in commensal E coli isolates from enrolled children before randomisation (37·7% of 406 isolates) despite only 3·7% of children having received a macrolide antibiotic during the hospitalisation. Azithromycin resistance was slightly higher at 3 months after randomisation in the azithromycin group (26·9%) than in the placebo group (19·1%; adjusted prevalence ratio 1·41, 95% CI 0·95–2·09, p=0·088), with no difference observed at 6 months (1·17, 0·78–1·76, p=0·44). Interpretation We did not observe a significant benefit of a 5-day course of azithromycin delivered to children younger than 5 years at hospital discharge despite the overall high risk of mortality and rehospitalisation. These findings highlight the need for more research into mechanisms and interventions for prevention of morbidity and mortality in the post-discharge period. Funding Eunice Kennedy Shriver National Institute of Child Health & Human Development.

Background Antibiotic and antiviral agents may be prescribed in patients with suspected or confirmed coronavirus disease 2019 (COVID-19) infections because of in vitro evidence of cessation of viral replication, potential bacterial secondary or coinfection, and inability to distinguish COVID-19 infections from common bacterial infections. The objective of this study was to evaluate antimicrobial prescribing patterns in the outpatient setting during the initial peak of COVID-19 in New York City. Methods This single-center, retrospective chart review included patients at least 18 years old who were prescribed oral antimicrobial agents in outpatient primary care clinics between March and May 2020. Data were compared with prescribing patterns from March to May 2019. The primary outcome was the number of antimicrobial prescriptions per 1000 patient visits. Secondary outcomes included documented indication, incidence of confirmed infections, mortality, and/or hospital admission within 90 days. Descriptive statistics were used. Results The overall antimicrobial prescribing rate increased from 31.94 prescriptions per 1000 visits in 2019 to 57.48 prescriptions per 1000 visits in 2020. Agents that were more commonly prescribed during the initial peak of COVID-19 include cefpodoxime, hydroxychloroquine, doxycycline, and sulfamethoxazole-trimethoprim. COVID-19 represented 7 (6%) documented antimicrobial indications in 2020, with agents such as azithromycin, hydroxychloroquine, doxycycline, cefpodoxime, and oseltamivir prescribed. Conclusions Overall antimicrobial prescribing rates in outpatient primary care clinics increased during the first peak of COVID-19 in an area with high infection burden. This increase may have been influenced by restricted patient evaluation, changes in patient management, and a decrease in overall patient visits.

RationaleInhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa. This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV1) and greater reduction in P. aeruginosa sputum in response to tobramycin.MethodsA 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and P. aeruginosa airway infection.ResultsOver a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV1 did not statistically significantly differ between groups (azithromycin (n=56) minus placebo (n=52) difference: 3.44%; 95% CI: −0.48 to 7.35; p=0.085). Differences in secondary clinical outcomes, including patient-reported symptom scores, weight and need for additional antibiotics, did not significantly differ. Among the 29 azithromycin and 35 placebo participants providing paired sputum samples, the 6-week change in P. aeruginosa density differed in favour of the placebo group (difference: 0.75 log10 CFU/mL; 95% CI: 0.03 to 1.47; p=0.043).ConclusionsDespite having greater reduction in P. aeruginosa density in participants able to provide sputum samples, participants randomised to placebo with inhaled tobramycin did not experience significantly greater improvements in lung function or other clinical outcomes compared with those randomised to azithromycin with tobramycin.

Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Lung transplant recipients are at increased risk for acquiring nontuberculous mycobacteria (NTM), but the clinical significance of NTM isolation, particularly among patients not meeting guideline-endorsed diagnostic criteria for NTM pulmonary disease, is unclear. Methods A case-control study of lung transplant recipients with culture-positive NTM infections treated at a large transplant center during a 7-year period (2013-2019) was performed. Results Twenty-nine cases were matched 1:2 to non-NTM controls. The median time to NTM isolation was 10.7 months post transplant. Only 34.5% of all cases, and half of treated cases, met diagnostic criteria for NTM pulmonary infection. All-cause mortality at 12 months was numerically higher among NTM cases versus controls (20.7% vs 8.6%, P = 0.169); however, no deaths were attributed to NTM. No increase in the 12-month rate of acute rejection was observed (27.6% vs 36.2%, P = 0.477). Recent augmented immunosuppression was associated with increased odds of NTM isolation, while azithromycin prophylaxis was associated with reduced odds of isolation and was not associated with macrolide resistance. Both adverse events and actual or potential drug-drug interactions occurred in more than 90% of treated cases; these events included ocular toxicity, hearing loss, and supratherapeutic calcineurin inhibitor concentrations. Eight of the 14 treated cases (57.1%) required early antibiotic discontinuation due to adverse events or drug-drug interactions. Conclusion Among lung transplant recipients, most patients with NTM isolation did not meet guideline criteria for infection and had outcomes similar to non‒NTM-infected patients, which may reflect transient lung colonization by NTM rather than true disease. As adverse events are common with NTM therapy, limiting unnecessary antibiotic treatment represents an area for future antimicrobial stewardship efforts.

Objective: The objective of this study is to assess adverse drug reaction (ADR) profile of the drugs prescribed to treat Coronavirus Disease (COVID-19) positive patients and to determine whether ADRs are associated with any comorbidities. Methods: A cross-sectional study was done with Laboratory confirmed COVID-19 positive patients who experienced ADRs during their admission period at tertiary care center, Rajkot from April 2020 to March 2021. All the necessary information including ADRs information was obtained from patient’s case record file and filled in suspected ADR reporting form. Suspected ADRs were assessed for demographic parameters and causality, preventability, and severity using World Health Organization (WHO) scale and Naranjo algorithm, modified Schumock and Thornton’s criteria, and modified Hartwig’s criteria, respectively. Results: Out of the 100 patients there were 60 males. The mean age of the patients was 52.65±13.95 year. Fourty-six patients had comorbidities. The most common type of ADR was GI disorders. Among the single suspected medication, most common drug was methylprednisolone and among the two drugs, azithromycin was common. According to the WHO and Naranjo scale, Probable ADRs were 70% and 36%, respectively. The percentage for mild, moderate and severe ADRs were 44%, 39%, 17%, respectively. Eighty-six percent ADRs were definitely preventable. Fifty-one patients were recovered from adverse reactions. Conclusions: Seriousness of reactions is mainly associated with co-morbid conditions. This indicates that patients with comorbidity should be closely monitored to avoid harmful consequences. These ADRs monitoring and reporting program will help physicians to choose their therapy sensibly and decrease chances of mortality in this pandemic era.

Non-tuberculous Mycobacterium (NTM) infections following knee surgery are rarely reported in the literature. One month after arthroscopic lysis of adhesions from anterior cruciate ligament (ACL) reconstruction, a 67-year-old male patient presented with symptoms suggesting septic arthritis. Empiric antibiotics were initiated. Intraoperative cultures were positive for Mycobacterium abscessus. Organism-specific antimicrobial therapy with azithromycin, amikacin, and imipenem were started. Four months later the patient was switched to oral outpatient treatment with azithromycin, clofazimine and bedaquiline. Mycobacterium infections following ACL reconstruction are exceedingly rare in the United States. Successful management of Mycobacterium abscessus infection is exceptionally challenging for both orthopedists and infection disease specialists.

Objective To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women. Methods We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate. Results From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection. Conclusion A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings. Clinical trial registration ClinicalTrials.gov, NCT03248297. Funding source Merck for Mothers Investigator Studies Program grant.

Background: The lack of effective medications for coronavirus disease 2019 (COVID-19) has led to a trend of drug repurposing such as the case of azithromycin which shows immunomodulatory and anti-viral effect. Several clinical trials have shown conflicting results. It is currently unclear whether the available evidence is in favor or against the use of azithromycin in COVID-19 patients. Thus, the aim of this study was to investigate the efficacy and safety of azithromycin in COVID-19 patients. Methods: Four independent reviewers selected relevant studies from PubMed, ScienceDirect, EBSCO, and ProQuest published prior to March 2021. The protocol used in this study has been registered in PROSPERO (CRD42020224967). Results: We included 17 studies and found that the mortality rate (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.76–1.19), need of respiratory support (OR, 1.30; 95% CI, 0.98–1.73), hospitalization rate (standardized mean difference, 0.12; 95% CI, –0.02 to 0.27), and intensive care unit transfer (OR, 1.21; 95% CI, 0.79–1.86) of azithromycin-treated group did not differ significantly (p>0.05) from those of the control group. Azithromycin treatment did not significantly increase the risk of getting secondary infection (OR, 1.23; 95% CI, 0.83–1.82), hypoglycemia (OR, 0.73; 95% CI, 0.38–1.40), gastrointestinal problems (OR, 1.03; 95% CI, 0.73–1.45) or electrocardiogram abnormalities (OR, 1.16; 95% CI, 0.94–1.42). The overall quality of evidence ranged from low to very low. Conclusion: Azithromycin did not result in a superior clinical improvement in COVID-19 patients, although it was well-tolerated and safe to use.

SUMMARY OBJECTIVE: With the coronavirus disease 2019 (COVID-19) continuing to spread all over the world, although there is no specific treatment until now, hydroxychloroquine and azithromycin have been reported to be effective in recent studies. Although long-term use of hydroxychloroquine and azithromycin has been reported to cause QT prolongation and malign arrhythmia, there is not enough data about the effect of short-term use on arrhythmia. Therefore, this study aims to assess the effect of hydroxychloroquine alone and hydroxychloroquine + azithromycin on corrected QT (QTc). METHODS: A baseline electrocardiogram and on-treatment baseline electrocardiogram were retrospectively collected in COVID-19 patients who received hydroxychloroquine and/or azithromycin. The QTc interval was calculated, and the baseline and peak QTc intervals were compared. In addition, the peak QTc intervals of monotherapy and combination therapy were compared. RESULTS: Of the 155 patients included, 102 (65.8%) patients were using hydroxychloroquine, and 53 (34.2%) patients were using hydroxychloroquine + azithromycin combination. The use of both hydroxychloroquine alone and hydroxychloroquine + azithromycin combined therapy significantly prolonged the QTc, and the QTc interval was significantly longer in patients receiving combination therapy. QTc prolongation caused early termination in both groups, 5 (4.9%) patients in the monotherapy group and 6 (11.3%) patients in the combination therapy group. CONCLUSION: In this study, patients who received hydroxychloroquine for the treatment of COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc.

Background The lack of medication standards is a serious problem in paediatrics mainly because of age-related differences in organ development and physiological functions in children. Consequently, dosage measurement becomes inaccurate. For this reason, methods for evaluating and monitoring rational paediatric medications should be developed. Drug use indicators, such as those similar to the drug utilisation index (DUI) based on the Anatomical Therapeutic Chemical/Defined Daily Dose (DDD) and widely used for the assessment of appropriate dosage in adults, should be explored in terms of their applicability to children. Methods A total of 5,538 prescriptions of antibiotics selected from a general teaching hospital were included. Drug, dose, frequency and treatment duration were obtained from each prescription. The prescription daily dose (PDD) of each antibiotic drug was calculated as the average of the daily doses. Underdose and overdose were determined in terms of the PDD/DDD ratio for each prescription. Children’s DUI (cDUI) was explored in terms of the appropriate dosage for children as follows: the meaning of children’s DDD (cDDD) and the evaluation of paediatric drug dosage. Results The top five antibiotics and their utilisation rates were as follows: cefmetazole sodium injection (18.47 %), erythromycin lactobionate injection (15.07 %), amoxicillin/clavulanate potassium injection (10.72 %), ceftriaxone sodium injection (9.50 %) and azithromycin dry suspension (8.02 %). The ratio of cDUI and PDD/cDDD was mostly not close to 1. Conclusions The establishment of a cDUI system is an effective means of paediatric dosage evaluation. In addition to DDDs, cDUI and PDD/cDDD should be used to analyse the utilisation of antibiotics in children.

Temporomandibular disorders (TMD) are conditions clinically characterized by pain and dysfunction in the masticatory muscles, temporomandibular joints (TMJs), and adjacent structures.The goal of treatment for TMDs is elimination or reduction of pain and maintain normal temporomandibular joint function, preventing further joint damage, and reducing disease-related morbidities. Immediate postoperative intra-articular drugs injections are currently being combined with arthrocentesis to treat both pain and the inflammatory disease process and improve outcomes. The aim of this study was to assess the efficacy of intra-articular injection of macrolides versus corticosteroids in improving outcomes after temporomandibular joint (TMJ) arthrocentesis in internal derangement (ID) of the joint due to anteriorly non reducing disc displacement.The study included 24 patients with internal derangement of the temporomandibular joint who did not respond to conservative treatment for 3 months. Patients were randomly divided into 2 equal groups according to the intra-articular drug injected after arthrocentesis. In group I, a corticosteroid is injected and in group II a macrolide with a known anti-inflammatory effect is used. Pain, mouth opening and analysis of Tumor Necrosis Factor-α (TNF-α) concentration were used as indicators of symptoms alleviation and patients improvement.In both groups, the median pain scores and MMO measurements after three months showed statistically significant lower values compared to pre-operative ones. In Conclusion, intra-articular injection of Azithromycin is comparable to corticosteroids injection as an effective method for treatment of the underlying disease process of internal derangement of the TMJ and alleviation of disease associated symptoms, such as pain and limitation of mouth opening. K

We here described a ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone (YL201) with moderate-level resistance to azithromycin in Shenzhen, South China in 2020. The NG-STAR type of YL201 is ST2238, containing a mosaic penA-60.001 allele, which is a typical characteristic of FC428 clone. YL201 harbours four copies of the 23S rRNA C2611T mutation, conferring moderate-level resistance to azithromycin. The MLST type is ST1600, identical with two N. gonorrhoeae FC428 clones identified in Hangzhou. Genome-wide phylogeny analysis demonstrates that YL201 is clustered with other FC428 clones from Hangzhou (South-east China) and Chengdu (South-west China). Isolates within this cluster have relatively higher MIC for ceftriaxone and display closely related MLST STs (ST1600 and ST7363) but are different from the ST of typical FC428 clone (ST1903). As ST1600 and ST7363 are common STs in Shenzhen, the further spread of FC428 clones may increase the severity of gonococcal resistance. In summary, identifying a multidrug-resistant (MDR) N. gonorrhoeae isolate in Shenzhen showed FC428 clones have undergone further transmission in China and presented more extensive and concerning antimicrobial resistance (AMR) characteristics during the spread.

According to the World Health Organisation, pneumonia and other lower respiratory tract infections are one of the leading causes of death all over the world. Simultaneous treatment of pneumonia with antibacterial drugs and concomitant medicines may result in adverse drug reactions (ADRs). The aim of the study was to analyse ADRs resulting from drug-drug interactions in different empiric antibiotic treatment regimens used for mild community-acquired pneumonia (CAP), taking into account the concomitant symptomatic non-antibacterial treatment and chronic disease treatment. Materials and methods: the authors analysed spontaneous reports in the VigiBase global database (starting from the date the database was created and until 15 February 2021) on ADRs resulting from interactions of medicinal products included in the Russian clinical guidelines for CAP. Results: the authors compiled a list of antibacterial drugs (amoxicillin+clavulanic acid, amoxicillin, ampicillin, azithromycin, clarithromycin, levofloxacin, moxifloxacin, cefotaxime, ceftriaxone, linezolid), as well as lists of medicinal products for symptomatic and concomitant treatment, based on the approved guidelines for management of CAP and frequent comorbid chronic diseases. They searched VigiBase for ADRs that may have resulted from drug-drug interactions involving these medicinal products. Conclusions: the analysis of adverse reactions used for mild CAP treatment demonstrated that the largest number of ADRs were associated with drug-drug interactions involving azithromycin, while the smallest number of ADRs were associated with cefotaxime and ceftriaxone. Further study of drug-drug interactions will help to prevent potential ADRs, identify rational drug combinations, and improve the existing patient management strategies.

Case Presentation A 30-year-old woman was referred with increasing shortness of breath and cough in the setting of GATA2 deficiency. She initially presented 9 years previously with recurrent episodes of pneumonia and sinusitis. Genetic testing revealed a heterozygous GATA2 mutation (c.988C>T). She has since had multiple infections that have included necrotizing fasciitis of the right thumb, recurrent pilonidal infections (which required 23 procedures), esophageal candidiasis, and human papillomavirus-positive high-grade squamous intraepithelial lesion of the cervix. Serial bone marrow biopsy specimens showed persistent hypocellularity (20% to 60%) with intermittent erythroid atypia and variable detection of trisomy 8, which were concerning for evolving myelodysplastic syndrome. One year before the current admission, she was diagnosed with disseminated Mycobacterium avium complex and was treated with rifabutin, ethambutol, and azithromycin. She was taking voriconazole, acyclovir, and trimethoprim-sulfamethoxazole prophylaxis.

A 74-year-old man with diabetic nephropathy undergoing dialysis after total knee arthroplasty presented to our hospital with dyspnea and abnormal behavior such as wearing his pants on his head. The patient was in shock with ventricular tachycardia. Urine and blood cultures showed MAM with sterile pyuria. We administered amikacin and imipenem cilastatin, but repeated cultures were persistently positive. Although we initially chose not to administer azithromycin because of a higher risk of fatal arrhythmia, we had no choice but to administer azithromycin because of treatment failure. Upon close monitoring, we observed no arrhythmia, and the blood cultures became negative. The patient was discharged on day 106 without any symptoms. However, 2 months after discontinuation of antibiotics, he was readmitted and diagnosed with prosthetic joint infection due to MAM. He could not undergo total knee arthroplasty resection because of his low tolerance to surgery. We re-administered same antibiotics, and repeated draining and cleaning of his left knee for several weeks. The inflammation in the knee joint gradually improved, and the patient was discharged while treatment with azithromycin and amikacin was continued. After being discharged, the patient did not experience recurrent disease for at least 6 months. Our case suggests that MAM can cause sterile pyuria and infection in a patient with diabetic nephropathy. The macrolide agent is a key drug for MAM infection, and repeated joint lavage in addition to administering antibiotics may be an alternative treatment for prosthetic joint infection in patients with intolerance to surgery.

Background: Although the burden of bronchiectasis is recognized globally, pediatric data are limited, particularly on trends over the years. Also, no published data exists regarding whether vitamin D deficiency or insufficiency and human T-cell lymphotropic virus type 1 (HTLV-1) infection, both found to be related to severe bronchiectasis in First Nations adults, also are important in children with bronchiectasis. Research Question: Among children with bronchiectasis, (1) have the clinical and BAL profiles changed between two 5-year periods (period 1, 2007-2011; period 2, 2012-2016) and (b) are vitamin D deficiency or insufficiency, HTLV-1 infection, or both associated with radiologic severity of bronchiectasis? Study Design and Methods: We analyzed the data from children with bronchiectasis prospectively enrolled at Royal Darwin Hospital, Australia, at the first diagnosis; that is, no child was included in both periods. Data collected include demographics, BAL, routine investigation bloods, and high-resolution CT scan of the chest evaluated using the Bhalla and modified Bhalla scores. Results: The median age of the 299 children was 2.2 years (interquartile range, 1.5-3.7 years). One hundred sixty-eight (56%) were male and most were First Nations (92%). Overall, bronchiectasis was high over time, particularly among First Nations children. In the later period, numbers of non-First Nations children more than tripled, but did not reach statistical significance. In period 2 compared with period 1, fewer First Nations children demonstrated chronic cough (period 1, 61%; period 2, 47%; P =.03), and were younger, First Nations children were less likely to have received azithromycin (period 1, 42%; period 2, 21%; P

Purpose This study set out to determine the antimicrobial resistance trends of Haemophilus influenzae isolates from pediatric hospitals in Mainland China, which would provide basis for clinical treatment. Methods The Infectious Disease Surveillance of Pediatrics (ISPED) collaboration group conducted this study. H. influenzae strains isolated from nine pediatric hospitals in Mainland China were included. Disk diffusion method was used for antimicrobial susceptibility test. Cefinase disc was used for detection of β-lactamase. Results In total, 13810 H. influenzae isolates were included during 2017–2019: 93.17% of which were from respiratory tract specimens, 4.63% from vaginal swabs, 1.10% from secretion, and 1.10% from others. Of all strains, 63.32% isolates produced β-lactamase; 8.22% isolates were β-lactamase-negative and ampicillin-resistant (BLNAR). The resistance to sulfamethoxazole-trimethoprim was 70.98%, followed by resistance to ampicillin (69.37%), cefuroxime (51.35%), ampicillin-sulbactam (38.82%), azithromycin (38.21%), amoxicillin-clavulanate (35.28%). More than 90% of H. influenzae isolates were susceptible to ceftriaxone, cefotaxime, meropenem, levofloxacin and chloramphenicol. The resistance rate of ampicillin and azithromycin in H. influenzae showed an increasing trend through the years. Statistically significant differences in antibiotic-resistance rates of all the antibiotics except chloramphenicol were found in different regions. The major Multi-Drug Resistance pattern was resistant to β-lactams, macrolides, and sulfonamides. Conclusions There is a rising trend of resistance rate of ampicillin and azithromycin in H. influenzae. Antimicrobial resistance of H. influenzae deserves our ongoing attention. Third-generation cephalosporin could be the preferred treatment option of infections caused by ampicillin-resistant H. influenzae.