Safety Of Azithromycin Research Articles

AN UPDATE ON CURRENT STATUS OF ANTIBIOTIC RESISTANCE IN SALMONELLA TYPHI: A RETROSPECTIVE ANALYSIS OF BLOOD CULTURE REPORTS FROM A TERTIARY CARE HOSPITAL

Background: Pakistan bears most of the burden of drug-resistant typhoid, challenging its healthcare systems with substantial cost. This study’s purpose is to investigate resistance in community-acquired salmonella typhi to guide its evidence-based empiric treatment. Methods: This study used retrospective data from the microbiology laboratory, Khyber Teaching Hospital, Peshawar (September 2022-March 2023). Data of routine diagnostic samples for typhoid was retrieved from the database. Kirby–Bauer disk diffusion method was employed to determine the sensitivity of S. Typhi against a panel of 21 selected antibiotic discs (not exclusively for each isolate). Results: Among 1742 suspected patients, 239 (13.92%) were positive for S. Typhi with 212/238 (89.1%), 227/233 (97.4%), and 196/239 (82.0%) isolates resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole, respectively. High resistance (88.0% to ciprofloxacin) was detected against fluoroquinolones. Third-generation cephalosporins also showed poor activity with 144/158 (91.1%) and 120/136 (88.2%) resistance towards ceftriaxone and cefixime, respectively, except for cefoperazone/sulbactam (2/123, 1.6%). Among 157 tested isolates, 3 (1.9%), 9 (5.7%), and 123 (78.3%) were labeled as non-resistant, MDR, and XDR strains, respectively. XDRs were less resistant to azithromycin (1/114), piperacillin/tazobactam (1/123), carbapenems (0/123), and tigecycline (0/123). Conclusion: XDR S. Typhi was observed as the dominant strain in Peshawar regions for which azithromycin is still the drug of choice. With emerging resistance, azithromycin safety should be ensured through antibiotic stewardship principles. An interesting finding was the enhanced activity of cefoperazone/sulbactam, suggesting future studies. Alternative options are expensive antibiotics which can be used as a last resort. Keywords: Typhoid, Antibiotic resistance, Extensive drug-resistant (XDR) S. Typhi, Pakistan.

Statistical analysis plan for the LAKANA trial: a cluster-randomized, placebo-controlled, double-blinded, parallel group, three-arm clinical trial testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1–11-month-old infants in Mali

BackgroundThe Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1–11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP).Methods/designLAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1–11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1–11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering.ConclusionThe SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results.Trial registrationClinicalTrials.gov ID NCT04424511. Registered on 11 June 2020.

Effectiveness And Safety of Azithromycin in Treatment of Covid-19: A Systematic Review

Effectiveness And Safety of Azithromycin in Treatment of Covid-19: A Systematic Review

A simple, high-throughput and validated LC-MS/MS method for the determination of azithromycin in human plasma and its application to a clinical pharmacokinetic study.

A sensitive, specific and rapid liquid chromatographic–tandem mass spectrometric (LC–MS/MS) method was developed and validated to quantify azithromycin concentrations in human plasma. Azithromycin (AZI) is the most common outpatient prescribed antibiotic in the US and clinical studies have demonstrated the efficacy and safety of AZI in many bacterial infections. To support a clinical study, we developed a high‐throughput LC–MS/MS method to process up to 250 samples per day to quantify AZI in human plasma. Samples were prepared by solid‐phase extraction. Separation was achieved with an ACE C18 column (2.1 × 100 mm, 1.7 μm) equipped with a C18 guard column. The mobile phase consisted of 0.1% formic acid and methanol–acetonitrile (1:1, v/v) at a flow rate of 0.25 ml/min. The ionization was optimized with positive electrospray source using multiple reaction monitoring transition, m/z 749.50 > 591.45 for AZI and m/z 754.50 > 596.45 for AZI‐d5. Extraction recoveries were approximately 90% for AZI. The assay was linear from 0.5 to 2,000 ng/ml and required only 100 μl of plasma with a total analysis time of 4.5 min. The method was successfully applied to pharmacokinetic studies of a weight‐based dosing protocol for AZI.

The efficacy and safety of azithromycin in treatment for childhood asthma: A systematic review and meta-analysis.

Azithromycin (AZI) is increasingly used for childhood asthma despite limited and inconsistent data. We aimed to evaluate the efficacy and safety of AZI in childhood asthma. We searched seven databases to include randomized controlled trials (RCTs) of AZI in the treatment of childhood asthma. Four reviewers independently screened the records. Risk of Bias 2 was used to assess the quality of RCTs. Risk ratioswith 95% confidence interval (CI) from dichotomous outcomes, and mean difference (MD) with 95% CI from continuous outcomes were pooled. We included 19 eligible reports from 17 studies. The prevalence of exacerbations in AZI + budesonide (BUD) + β2 agonist (BA) group was lower than BUD + BA group (four [13%] vs. 19 [63%], p < 0.05) in 6- 14 years old children with chronic persistent asthma. AZI plus antiasthma drugs (AADs) could improve the posttreatment childhood asthma control test score (MD = 2.97; 95% CI, 2.39-3.54) compared to AADs alone in children with chronic persistent asthma. AZI plus AADs could improve posttreatmentforced expiratory volume in 1 s of predicted value/forced vital capacity % (MD = 10.24%; 95% CI, 6.44%-14.03%) and posttreatment peak expiratory flow % of predicted value (MD = 7.00%; 95% CI, 2.53%-11.47%) compared to AADs alone in children with chronic persistent asthma. The most common adverse reactions of AZI combined with other drugs were gastrointestinal reactions. AZI may be beneficial in improving some clinical symptoms and lung functions in older asthma children (over 6 years old) with persistent asthma. But it still requires further research.

Efficacy and safety of azithromycin in Covid-19 patients: A systematic review and meta-analysis of randomized clinical trials.

SummaryAzithromycin (AZM) is commonly used in Covid‐19 patients based on low‐quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta‐analysis investigated the safety and efficacy of AZM in treating Covid‐19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random‐effects model was used to pool estimates using the Paule–Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as ‘low’ for five of the seven mortality results and as ‘some concerns’ and ‘high’ in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid‐19 patients (OR = 0.96, 95% CI 0.88–1.05, p = 0.317 based on the random‐effect meta‐analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49–1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI −2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid‐19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.

Efficacy and safety of azithromycin and amoxicillin/clavulanate for otitis media in children: a systematic review and meta-analysis of randomized controlled trials

BackgroundResistance, prolonged therapy, and more adverse reactions made amoxicillin less preferred for treating otitis media. This study aimed to compare the efficacy and safety of azithromycin and amoxicillin/clavulanate for the treatment of otitis media in children.MethodologyThis study was a systematic review and meta-analysis. PubMed, Cochrane library, and Google scholar databases were searched. Comparative randomized clinical trial studies between azithromycin and amoxicillin/clavulanate to treat otitis media in children published up to 30 September 2019 were included. The risk of bias was assessed and Data was extracted by the first author and checked by the second author. Meta-analysis was performed by STATA software version 16, and Mantel–Haenszel statistical method with effect measure odds ratio was employed for analysis.Result751 records were identified and 14 studies were eligible for analysis. In 12 studies azithromycin had equivalent clinical efficacy and 2 had less to amoxicillin/clavulanate. Meta-analysis results showed no statistically significant difference in efficacy in favor of amoxicillin/clavulanate after completion of treatment OR 0.75, 95% CI (0.62–0.91). On subgroup analysis for children less than 2 years (OR 0.96 95% CI (0.49–2.29), and greater than 2 years (OR 1.40 95% CI (0.93–2.11) and also efficacy on follow up (OR 0.97 95% CI (0.83–1.15) there is no statistically significant difference. The clinical adverse events are more in the amoxicillin/clavulanate group than in the azithromycin with a statistical significant difference OR 0.46 95% CI (0.43–0.56).ConclusionAzithromycin is comparable to amoxicillin/clavulanate to treat otitis media in children, and it is safer and more tolerable.

Short-Course Azithromycin for Lower Respiratory Tract Infection in Adults

Abstract Azithromycin, a macrolide antibiotic, has been shown to be effective in community-acquired pneumonia (CAP). The long half-life of azithromycin allows for a shortened treatment course, whereas the drug level is sufficiently maintained in the blood. The objective of this study is to review the body of evidence on the efficacy and safety of azithromycin in CAP treatment given as a regimen of 500 mg daily for 3 days. An English-language literature search was completed through PubMed (1980–2019). Full-text studies conducted in humans to compare a 5-day azithromycin course with a 3-day azithromycin course or azithromycin with other antibiotics for CAP treatment were included. Although the standard recommended CAP treatment regimen of azithromycin is 1500 mg in a total dose divided for 5 days, the efficacy of 1500 mg in a total dose divided for 3 days has been shown to be as effective as the 5-day course and comparable to longer durations of clarithromycin or amoxicillin/clavulanate for CAP treatment in an outpatient setting. Meanwhile, the evidence is less supportive of the use of 3-day azithromycin in patients who require hospitalization. The risk of cardiac death is low and not greater than the risk with other antibiotics.

Resumption/efficacy and safety of an azithromycin-containing regimen against Mycobacterium avium complex lung disease in patients who experienced adverse effects with a clarithromycin-containing regimen.

Antibiotic therapy, including clarithromycin (CLR), has been widely used for the management of Mycobacterium avium complex (MAC) lung disease in clinical settings. When patients develop adverse events (AEs) during CLR-based treatment, the treatment regimen is modified or chemotherapy itself is discontinued. The need for alternative macrolide treatment strategies is emphasized due to the high rate of AEs possibly caused by CLR. Thus, the current study aimed to examine the efficacy and safety of azithromycin (AZM) in patients with MAC lung disease whose treatment was switched from CLR to AZM. We performed a retrospective study of patients with MAC lung disease. The inclusion criteria were as follows: (1) patients who experienced AEs during treatment with antibiotics, including CLR, between December 2012 and November 2017, and (2) those who had antimicrobial therapy that was switched from CLR to AZM. The efficacy and safety of AZM during the clinical course of the disease after switching the regimen from CLR to AZM were investigated. Antibiotic therapy was switched in 31 patients who presented with AEs including drug-induced fever, rash, dysgeusia, liver dysfunction, and neutropenia during treatment with CLR-containing regimens. After switching to AZM, the median duration of treatment was 1286 (364-4615) days. During follow-up, 13 patients had a negative conversion of sputum culture. AZM may be safe and effective for patients with MAC lung disease who have difficulty tolerating CLR. In patients who experienced AEs possibly caused by CLR, switching from CLR to AZM might be an appropriate strategy.

Effectiveness and safety of azithromycin 1.5% eye drops for mass treatment of active trachoma in a highly endemic district in Cameroon

ObjectiveTo evaluate the effectiveness and safety of azithromycin 1.5% eye drops under field conditions to reduce active trachoma in a highly endemic district in Cameroon. This is a follow-up of...

Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial

BackgroundThe efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19.MethodsWe did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278.Findings447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94–1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups.InterpretationIn patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19.FundingCOALITION COVID-19 Brazil and EMS.

Safety of azithromycin in pediatrics: a systematic review and meta-analysis

PurposeTo evaluate the toxicity of azithromycin in neonates, infants, and children.MethodsA systematic review was performed for relevant studies using Medline (Ovid), PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and International Pharmaceutical s. We calculated the pooled incidence of adverse drug reactions (ADRs) associated with azithromycin based on prospective studies (RCTs and prospective cohort studies) and analyzed the risk difference (RD) of ADRs between azithromycin and placebo or other antibiotics using meta-analysis of RCTs.ResultsWe included 133 studies with 4243 ADRs reported in 197,675 neonates, infants, and children who received azithromycin. The safety of azithromycin as MDA in pediatrics was poorly monitored. The main ADRs were diarrhea and vomiting. In prospective non-MDA studies, the most common toxicity was gastrointestinal ADRs (938/1967; 47.7%). The most serious toxicities were cardiac (prolonged QT or irregular heart beat) and idiopathic hypertrophic pyloric stenosis (IHPS). Compared with placebo, azithromycin did not show increased risk ADRs based on RCTs (risk difference − 0.17 to 0.07). The incidence of QT prolonged was higher in the medium-dosage group (10–30 mg/kg/day) than that of low-dosage group (≤ 10 mg/kg/day) (82.0% vs 1.2%).ConclusionThe safety of azithromycin as MDA needs further evaluation. The most common ADRs are diarrhea and vomiting. The risk of the most serious uncommon ADRs (cardiac-prolonged QT and IHPS) is unknown.

Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19

Aims: The challenge regarding COVID-19 is to prevent complications and fatal evolution. Azithromycin (AZM) and hydroxychloroquine (HCQ) have proven their antiviral effect in vitro. We aimed to assess the efficacy and safety of AZM alone or combined to HCQ, prescribed, at an early stage, in patients with Covid-19, in a primary care setting.&#x0D; Study Design: Retrospective observational study.&#x0D; Place and Duration of Study: Patients have been followed by private practitioners in France, between March and April 2020.&#x0D; Methodology: Eighty-eight patients received either no or a symptomatic treatment (NST) (n=34) or AZM alone (n=34) or AZM+HCQ (n=20). The efficacy end point was the time to clinical recovery and the safety end point was the occurrence of cardiovascular events. To improve the evidence level, a case-control analysis was performed on a sample of 57 patients (19/group) matched for age, sex and BMI.&#x0D; Results: The mean (SD) times to achieve clinical recovery were respectively 25.8 days (11.1), 12.9 days (13.4) and 9.2 days (9.3), showing a statistically significant difference between NST and AZM alone (p&lt;0.0001) or AZM+HCQ (p&lt;0.0001). The statistical difference between NST and AZM was confirmed (p=0.0149) as well as the difference with AZM+HCQ (p=0.0002). No cardiac toxicity was recorded in any patient. No statistical difference was shown between AZM and AZM+HCQ groups, although the dual therapy tended to be more effective in patients over 50 years, based on an analysis using the cox model.&#x0D; Conclusion: AZM and AZM+HCQ favourably impacted the course of the disease. We need trials, ideally prospective/double blind, to show if a statistical difference can be evidenced with a broader group, and clarify the indications of each treatment depending on initial clinical presentation.

The efficacy and safety of azithromycin in chronic respiratory diseases related cough.

Azithromycin is potential for preventing exacerbations in chronic respiratory diseases. However, rare attention was paid to the cough symptom of such airway diseases by azithromycin intervention. We summarized the efficacy and safety of azithromycin in chronic respiratory diseases related cough. We searched 4 electronic databases (PubMed, EMBASE, Cochrane, and Web of Science) to identify randomized controlled trials (RCTs) comparing the change of Leicester Cough Questionnaire (LCQ) score, cough visual analogue scale (VAS) and side effects of azithromycin in patients of chronic respiratory diseases with cough. We identified 5 RCTs (n=879 patients) in pooled analyses. Compared to placebo, azithromycin intervention had no effect in reducing cough [mean difference (MD) 0.73; 95% CI: -0.78 to 2.24; P=0.34] with significant heterogeneity (P=0.03, I2 =71%). However, heterogeneity is caused by one study. After removal of this study, azithromycin administration had shown clinically important improvement in LCQ score (MD 1.30; 95% CI: 1.15-1.46; P<0.00001; I2 =0%). In addition, no significant difference was detected in adverse events and azithromycin administration probably had less central nervous system side effects for chronic respiratory diseases with cough. The addition of oral azithromycin may result in significant benefit for chronic respiratory diseases related cough. Azithromycin was safe for those patients with cough.

Chloroquine or Hydroxychloroquine for COVID-19: Is Cardiotoxicity a Concern?

Chloroquine or Hydroxychloroquine for COVID-19: Is Cardiotoxicity a Concern?

Should azithromycin be used to treat COVID-19? A rapid review.

BackgroundThere are no established effective treatments for COVID-19. While novel drugs are being developed, azithromycin has been identified as a candidate treatment in the interim.AimTo review the evidence for the effectiveness and safety of azithromycin in treating COVID-19.Design & settingA rapid review of the literature was conducted.MethodElectronic searches were conducted on 16 April 2020 of PubMed, TRIP, EPPI COVID Living Map, MedRxiv, GoogleScholar, and Google. In vivo and in vitro studies were included assessing the safety and effectiveness of azithromycin for treatment of COVID-19, and/or the activity of azithromycin against SARS-CoV-2. In vivo studies needed to include a comparator group.ResultsThree studies were identified, two in vitro and one in vivo, which were suitable for inclusion. All three were published as pre-prints. The in vitro studies revealed conflicting results, with one finding anti-SARS-CoV-2 activity for azithromycin alone, while the other found activity against SARS-CoV-2 only when azithromycin was combined with hydroxychloroquine. A small trial of 36 patients, with high risk of bias, found superior viral clearance in patients with COVID-19 treated with azithromycin and hydroxychloroquine combined, compared with hydroxychloroquine alone.ConclusionThere is no evidence to support the use of azithromycin for the treatment of COVID-19 outside of the context of clinical trials, unless it is used to treat bacterial super-infection. There is extremely limited evidence of a possible synergy between azithromycin and hydroxychloroquine. The adverse events profile of azithromycin in the context of COVID-19 has not yet been established. Well-conducted clinical trials are urgently needed in this area.

The efficacy and safety of long-term add-on treatment of azithromycin in asthma: A systematic review and meta-analysis.

Aim:Effects of azithromycin on asthma reported in clinical trials are less consistent. We aimed to further clarify the efficacy and safety of azithromycin in treatment of asthma.Methods:The protocol registration number was CRD42017074318 (http://www.crd.york.ac.uk/Prospero). We searched PubMed, EMBASE, Cochrane databases, China National Knowledge Internet (CNKI), and Wanfang databases for the randomized controlled trials (RCTs) with prolonged treatment of azithromycin for more than 3 weeks. Random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference (MD) for dichotomous and continuous data respectively.Results:A total of eight studies were included for analysis. The pooled result of adjunctive azithromycin therapy in asthma showed a small, but statistically significant increase in forced expiratory volume in one second (FEV1) (MD = 0.06, 95% confidence interval [CI]: 0.01–0.12, P = .02), but no significant differences in exacerbation frequency (MD = −0.42, 95%CI: −1.13 to 0.30, P = .25) and peak expiratory flow (PEF) (MD = 0.20, 95% CI: −0.05 to 0.44, P = .12), fractional exhaled nitric oxide (FeNO) (MD = 4.12, 95% CI: −2.06 to 10.30, P = .19), asthma quality of life questionnaire (AQLQ) (MD: 0.05, 95% CI: −0.17 to 0.28, P = .65), asthma control questionnaire (ACQ) (MD: −0.03, 95% CI: −0.21 to 0.15, P = .75). The subgroup analysis revealed that azithromycin could decrease FeNO among Asian asthma (MD = 15.04, 95% CI: 6.18–23.90, P = .0009).Conclusions:Add-on therapy of azithromycin in asthma patients could improve the FEV1, but failed to improve asthma exacerbations, PEF, ACQ, AQLQ, and FeNO. Subgroup analysis indicated that azithromycin could improve FeNO in Asian group asthmatics.

A randomized controlled trial of azithromycin and sulphadoxine–pyrimethamine as prophylaxis against malaria in pregnancy among human immunodeficiency virus–positive women

Malaria and human immunodeficiency virus (HIV) infections in pregnancy are important and major contributing factors to maternal morbidity and mortality in sub-Saharan Africa. Prevention of malaria in HIV-positive pregnant woman will reduce the burden of malaria-HIV comorbidity. The objective of this study was to compare effects and safety of azithromycin (AZ) with sulphadoxine-pyrimethamine (SP) for intermittent preventive therapy for malaria in HIV-positive pregnant women. We performed a randomized, controlled, open-label pregnancy trial of 140 HIV-positive pregnant patients attending antenatal clinics at the University College Hospital and Adeoyo Maternity Teaching Hospital, Ibadan, Nigeria. Participants were enrolled from a gestational age of 16 weeks and randomized to receive AZ or SP. The primary outcome was peripheral parasitaemia at delivery. Secondary outcomes were drug tolerability, foetal outcome and birthweight. The χ2 test (or Fisher's exact test, as appropriate) and Student's t test were used in the per-protocol analysis. The level of statistical significance was p<0.05. A total of 123 participants (87.9%) completed the study: 60 participants received AZ and 63 received SP. The incidence of malaria parasitaemia at delivery in the AZ group was 6 (10.0%), compared with 7 (11.1%) in the SP group (relative risk 0.89 [95% confidence interval 0.28 to 2.82], p=0.84). Placental parasitization was demonstrated in 1 (1.6%) participant in the SP group compared with 3 (5.0%) in the AZ group (p=0.36). The findings suggest that AZ is comparable to SP in malaria prevention and safety in HIV-positive pregnant women.

Efficacy and Safety of Azithromycin and Ofloxacin in Uncomplicated Typhoid Fever, in Tertiary Care Hospital at S.K.M.C.H., Muzaffarpur, Bihar

Efficacy and Safety of Azithromycin and Ofloxacin in Uncomplicated Typhoid Fever, in Tertiary Care Hospital at S.K.M.C.H., Muzaffarpur, Bihar

Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies

Lacking protective antibodies, patients with primary antibody deficiencies (PADs) experience frequent respiratory tract infections, leading to chronic pulmonary damage. Macrolide prophylaxis has proved effective in patients with chronic respiratory diseases. We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs. We designed a 3-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250mg administered once daily 3 times a week for 2years) would reduce respiratory exacerbations in patients with PADs and chronic infection-related pulmonary diseases. The primary end point was the number of annual respiratory exacerbations. Secondary end points included time to first exacerbation, additional antibiotic courses, number of hospitalizations, and safety. Eighty-nine patients received azithromycin (n=44) or placebo (n=45). The number of exacerbations was 3.6 (95% CI, 2.5-4.7) per patient-year in the azithromycin arm and 5.2 (95% CI, 4.1-6.4) per patient-year in the placebo arm (P=.02). In the azithromycin group the hazard risk for having an acute exacerbation was 0.5 (95% CI, 0.3-0.9; P=.03), and the hazard risk for hospitalization was 0.5 (95% CI, 0.2-1.1; P=.04). The rate of additional antibiotic treatment per patient-year was 2.3 (95% CI, 2.1-3.4) in the intervention group and 3.6 (95% CI, 2.9-4.3) in the placebo group (P=.004). Haemophilus influenzae and Streptococcus pneumoniae were the prevalent isolates, and they were not susceptible to macrolides in 25% of patients of both arms. Azithromycin's safety profile was comparable with that of placebo. The study reached the main outcome centered on the reduction of exacerbation episodes per patient-year, with a consequent reduction in additional courses of antibiotics and risk of hospitalization.