[Investigation on the rational use of antibacterial agents by Chinese pediatricians in 2016].
Zhonghua er ke za zhi = Chinese journal of pediatrics
To obtain baseline data of pediatricians' clinical use of antibacterial agents in children in China, and provide evidence for the follow-up of guidelines for the diagnosis and treatment of children's clinical medications and the development of rational drug management measures and norms. A multi-center cross-sectional study was designed to conduct a network electronic questionnaire survey of doctors with child prescription rights in hospitals of all provinces, municipalities and autonomous regions across the country through cluster sampling to understand the current status of antibacterial drugs use in 2016. The survey information of 3 494 pediatricians in tertiary hospitals was finally included. (1) Ranking of the importance of children's medication focus: 54.5% of doctors ranked first the "safety" and 43.5% ranked second the "efficacy" . (2) The most urgent antibacterial agents for children are reported as macrolides (11.9%), third-generation cephalosporins (4.8%), penicillins (4.2%), sulfonamides (2.5%), and carbapenems (2.4%). (3) The top five drugs that are urgently needed to obtain children's indications are: macrolides (26.4%), quinolones (19.9%), aminoglycosides (10.4%), and other antibacterials (9.0%) and the 3rd generation cephalosporins (5.1%). (4) For children with bacterial upper respiratory tract infections, antibacterial drugs should be used in the order of penicillins, second-generation cephalosporins, third-generation cephalosporins, azithromycin or erythromycin, medicamycin or unscented erythromycin or ester erythromycin. (5) The most important basis for empirical use of antibacterials, 42.0% of doctors chose "clinical signs and symptoms", followed by "imaging results" (41.0%). (6) 87.0% of the doctors chose" to read the drug instructions manual before using the drug" as the main way to understand the drug; for the adverse reactions of the antibacterial drugs, the top three rankings of the surveyed doctors were "allergic reactions" (93.3%). "hepatic/kidney functional side effects" (91.1%) and "myelosuppression" (48.2%). (7) The three main problems of children's drug risk selected by the surveyed doctors are "lack of indications for children's medication" (85.5%), "abuse of antimicrobials" (71.2%) and"formulations and specifications for lack of children's drugs". (69.2%). (8) The key link for children's rational drug use, the choice of the doctors to investigate is "clarifying and improving the indications for children's medication" (89.0%), "strengthening the rational use of drugs and clinical guidelines for children" (66.2%) and "developing and producing pharmaceutical dosage form for children and its specifications" (62.6%). Pediatricians are generally reasonable in the basic concepts and knowledge, attitudes and practices of rational use of antibiotics: they can put the safety of medications first, pay attention to reading the instructions before using drugs, and pay attention to the adverse reactions of children. For the drugs that result in adverse reactions in children, it is urgent to understand their indications. Pediatricians use clinical symptoms, signs and imaging findings as an empirical basis for the selection of drugs for bacterial upper respiratory tract infections and antimicrobial agents. The investigation found that macrolides, third-generation cephalosporins, penicillins and other drugs are the most urgent antibacterial drugs in pediatrics, and found that a considerable number of antibacterials lack the indications for children, lack of dosage forms and specifications for children, presence of abuse, etc. The problem is that there are hidden dangers in the use of antibiotics in children. The survey concluded that for pediatricians, the basic concepts and knowledge, attitudes and practices of the rational use of antimicrobials continue to be strengthened. It is necessary to clarify and improve the indications for children's medications, strengthen the training of rational medications and clinical guidelines, and vigorously develop and produce children's medicine dosage forms and their specifications for existing antibacterial drugs. All these are the key links for children's rational use of antibacterials.
10.3760/cma.j.issn.0578-1310.2018.12.004
Considerations for a Pediatric Biopharmaceutics Classification System (BCS): application to five drugs.
Gandhi Shivani V,Rodriguez William,Khan Mansoor,Polli James E
AAPS PharmSciTech
It has been advocated that biopharmaceutic risk assessment should be conducted early in pediatric product development and synchronized with the adult product development program. However, we are unaware of efforts to classify drugs into a Biopharmaceutics Classification System (BCS) framework for pediatric patients. The objective was to classify five drugs into a potential BCS. These five drugs were selected since both oral and intravenous pharmacokinetic data were available for each drug, and covered the four BCS classes in adults. Literature searches for each drug were conducted using Medline and applied to classify drugs with respect to solubility and permeability in pediatric subpopulations. Four pediatric subpopulations were considered: neonates, infants, children, and adolescents. Regarding solubility, dose numbers were calculated using a volume for each subpopulation based on body surface area (BSA) relative to 250 ml for a 1.73 m(2) adult. Dose numbers spanned a range of values, depending upon the pediatric dose formula and subpopulation. Regarding permeability, pharmacokinetic literature data required assumptions and decisions about data collection. Using a devised pediatric BCS framework, there was agreement in adult and pediatric BCS class for two drugs, azithromycin (class 3) and ciprofloxacin (class 4). There was discordance for the three drugs that have high adult permeability since all pediatric permeabilities were low: dolasetron (class 3 in pediatric), ketoprofen (class 4 in pediatric), and voriconazole (class 4 in pediatric). A main contribution of this work is the identification of critical factors required for a pediatric BCS.
10.1208/s12249-014-0084-0
Safety of azithromycin in pediatric infectious diseases: a clinical systematic review and meta-analysis.
Translational pediatrics
BACKGROUND:Azithromycin is a second-generation macrolide antibiotic which can be used in the treatment of diseases caused by sensitive bacterial infections. This article aimed to investigate the safety of azithromycin in the treatment of infectious diseases in children by meta-analysis. METHODS:PubMed, Embase, and Cochrane were selected as the search database platforms. Randomized controlled trials (RCTs) published after 2010 were searched using the following keywords: "azithromycin", "children", "adverse event", "intravenous event", and "oral". Included studies were all clinical trials of azithromycin in the treatment of pediatric diseases. After inclusion/exclusion criteria screening and bias risk assessment, data were extracted from the included studies. RevMan 5.3.5 software was used for statistical analysis to obtain both forest and funnel plots. RESULTS:A total of nine articles involving 3,597 pediatric patients were included in this study. The results of meta-analysis showed that the nine articles exhibited statistical heterogeneity (I=70%; P=0.001), and thus, a random-effects model was used. The obtained statistic was [odds ratio (OR) =0.65; 95% confidence interval (CI): (0.43, 0.97)], the statistical effect value was Z=2.10, P=0.04, and the difference was statistically significant. After excluding one article, the remaining eight articles showed homogeneity (I=12%; P=0.34). So, using fixed-effects model analysis, the statistic was [OR =0.79; 95% CI: (0.67, 0.94)], and the effect size value was Z=2.73, P=0.006. DISCUSSION:Compared with other antibiotics, the clinical safety of azithromycin is relatively good, but care should be taken when the dosage is high in treating some disease.
10.21037/tp-21-444
Pharmacokinetics of intravenously administered azithromycin in pediatric patients.
Jacobs Richard F,Maples Holly D,Aranda Jacob V,Espinoza Gabriela M,Knirsch Charles,Chandra Richa,Fisher Jeannine M,Kearns Gregory L
The Pediatric infectious disease journal
BACKGROUND:The objective of this study was to characterize the pharmacokinetics and tolerance of a single intravenous (IV) azithromycin dose in children. METHODS:Subjects were stratified into 4 age groups: 0.5-2 years; >2-<6 years; 6-<12 years; and 12-<16 years. Each subject received a single 10 mg/kg dose (500 mg maximum) infused in 1 hour. Serial venous blood samples were obtained for a 168-hour period, and laboratory safety evaluations were performed immediately preceding azithromycin administration and at the conclusion of the study. Serum azithromycin concentrations were quantified with a validated high performance liquid chromatography method with mass spectrometric detection. Pharmacokinetic indices were calculated for each subject by noncompartmental techniques. RESULTS:Thirty-two subjects (6.7 +/- 5.0 years, 11 boys) participated. Mean serum concentration-time data were comparable for the 4 age groups. For all subjects with evaluable data, the mean area under the curve from 0 to 72 hours (AUC0-72) was 8.2 microg . h/mL (n = 26), the maximum concentration (Cmax) was 2.4 microg/mL and the elimination half-life (t1/2) was 65.2 hours (n = 25). The AUC0-72 and Cmax were not associated with age. The dose was well-tolerated with no serious adverse events. CONCLUSION:The disposition of azithromycin after a single 10-mg/kg IV dose (maximum labeled adult dose of 500 mg) is comparable in pediatric patients between 0.5 and 16 years of age. These pharmacokinetic data can be used to guide dose selection for future therapeutic trials of IV azithromycin in pediatric patients.
Azithromycin and the risk of cardiovascular complications.
Maisch Nicole M,Kochupurackal Jenny G,Sin Jonathan
Journal of pharmacy practice
The purpose of this review was to evaluate the literature to assess the incidence and true clinical relevance of recent Food and Drug Administration warnings regarding QT prolongation with azithromycin, given its widespread use, with over 40 million US outpatient prescriptions written in 2011. A literature search of MEDLINE (1946 to May 2013) and International Pharmaceutical Abstracts (1970 to May 2013) was conducted using the terms azithromycin, QT prolongation, torsades de pointes, arrhythmia, and cardiovascular death. A bibliographic search was also performed. Several relevant studies and case reports were identified and reviewed. One cohort study revealed an increased risk of cardiovascular death with azithromycin compared to no antibiotic, especially in those with higher cardiovascular risk. Another cohort study comparing azithromycin, penicillin V, and no antibiotic in a younger Danish population with less cardiac risk found no increased cardiovascular death associated with azithromycin use. The majority of case reports involved ill and/or elderly patients with multiple comorbidities and concomitant medications who were already at a higher risk of cardiovascular events. Although there is evidence that azithromycin may induce QT prolongation and adverse cardiac events, the incidence is fairly limited to patients with high baseline risk, including those with preexisting cardiovascular conditions and concomitant use of other QT-prolonging drugs.
10.1177/0897190013516503
Cardiac Arrest in Pediatric Patients Receiving Azithromycin.
Valdés Santiago O,Kim Jeffrey J,Niu Mary C,de la Uz Caridad M,Miyake Christina Y,Moffett Brady S
The Journal of pediatrics
OBJECTIVE:To compare outcomes of pediatric patients treated with azithromycin compared with penicillin or cephalosporin. We hypothesized that azithromycin use would not be associated with increased cardiac mortality in the pediatric population. STUDY DESIGN:Retrospective cohort study from the Pediatric Health Information System database between 2008 and 2012. Patients <19 years of age with a principal diagnosis of community-acquired pneumonia who received an antibiotic were included. Primary outcomes were cardiopulmonary resuscitation (CPR) and mortality. Secondary outcomes were ventricular arrhythmias incidences and readmission for ventricular arrhythmia. Statistical analysis was performed with the χ test. Multivariable analysis was performed to control for potential confounders among patient, event, and treatment characteristics. RESULTS:A total of 82 982 patients (54.3% males) met study criteria. Median age was 2.6 years (IQR 1.2-5.9 years) and median length of stay was 2 days (IQR 2-4 days). Azithromycin was used in 5039 (6.1%); penicillin or cephalosporin was used in 77 943 (93.9%). Overall prevalence of antibiotic-associated CPR was 0.14%. Patients receiving a macrolide antibiotic had a lower prevalence of CPR compared with patients receiving a penicillin or cephalosporin (0.04% vs 0.14%, P = .04), and there was no difference in mortality. Multivariable analysis did not find an association between macrolide use and CPR. CONCLUSIONS:In contrast to recent adult studies, among children hospitalized for community-acquired pneumonia, azithromycin use was not associated with a greater prevalence of cardiac arrest compared with penicillin or cephalosporin use.
10.1016/j.jpeds.2016.11.012
Azithromycin Causes a Novel Proarrhythmic Syndrome.
Yang Zhenjiang,Prinsen Joseph K,Bersell Kevin R,Shen Wangzhen,Yermalitskaya Liudmila,Sidorova Tatiana,Luis Paula B,Hall Lynn,Zhang Wei,Du Liping,Milne Ginger,Tucker Patrick,George Alfred L,Campbell Courtney M,Pickett Robert A,Shaffer Christian M,Chopra Nagesh,Yang Tao,Knollmann Bjorn C,Roden Dan M,Murray Katherine T
Circulation. Arrhythmia and electrophysiology
BACKGROUND:The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells. METHODS AND RESULTS:In conscious telemetered mice, acute intraperitoneal and oral administration of azithromycin caused effects consistent with multi-ion channel block, with significant sinus slowing and increased PR, QRS, QT, and QTc intervals, as seen with azithromycin overdose. Similarly, in HL-1 cardiomyocytes, the drug slowed sinus automaticity, reduced phase 0 upstroke slope, and prolonged action potential duration. Acute exposure to azithromycin reduced peak SCN5A currents in HEK cells (IC=110±3 μmol/L) and Na current in mouse ventricular myocytes. However, with chronic (24 hour) exposure, azithromycin caused a ≈2-fold increase in both peak and late SCN5A currents, with findings confirmed for I in cardiomyocytes. Mild block occurred for K currents representing I (CHO cells expressing hERG; IC=219±21 μmol/L) and I (CHO cells expressing KCNQ1+KCNE1; IC=184±12 μmol/L), whereas azithromycin suppressed L-type Ca currents (rabbit ventricular myocytes, IC=66.5±4 μmol/L) and I (HEK cells expressing Kir2.1, IC=44±3 μmol/L). CONCLUSIONS:Chronic exposure to azithromycin increases cardiac Na current to promote intracellular Na loading, providing a potential mechanistic basis for the novel form of proarrhythmia seen with this macrolide antibiotic.
10.1161/CIRCEP.115.003560
Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death.
Rao Gowtham A,Mann Joshua R,Shoaibi Azza,Bennett Charles Lee,Nahhas Georges,Sutton S Scott,Jacob Sony,Strayer Scott M
Annals of family medicine
PURPOSE:Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin. METHODS:We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days. RESULTS:During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20-2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56-3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32-2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09-2.82). CONCLUSIONS:Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.
10.1370/afm.1601
Risks of cardiac arrhythmia and mortality among patients using new-generation macrolides, fluoroquinolones, and β-lactam/β-lactamase inhibitors: a Taiwanese nationwide study.
Chou Hsu-Wen,Wang Jiun-Ling,Chang Chia-Hsuin,Lai Chao-Lun,Lai Mei-Shu,Chan K Arnold
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:Previous studies have demonstrated increased cardiovascular mortality related to azithromycin and levofloxacin. Risks associated with alternative drugs in the same class, including clarithromycin and moxifloxacin, were unknown. We used the Taiwan National Health Insurance Database to perform a nationwide, population-based study comparing the risks of ventricular arrhythmia and cardiovascular death among patients using these antibiotics. METHODS:Between January 2001 and November 2011, a total of 10 684 100 patients were prescribed oral azithromycin, clarithromycin, moxifloxacin, levofloxacin, ciprofloxacin, or amoxicillin-clavulanate at outpatient visits. A logistic regression model adjusted for propensity score was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for adverse cardiac outcomes occurring within 7 days after the initiation of antibiotic treatment. RESULTS:Compared with amoxicillin-clavulanate treatment, the use of azithromycin and moxifloxacin was associated with significant increases in the risks of ventricular arrhythmia and cardiovascular death. The adjusted ORs for ventricular arrhythmia were 4.32 (95% CI, 2.95-6.33) for azithromycin, 3.30 (95% CI, 2.07-5.25) for moxifloxacin, and 1.41 (95% CI, .91-2.18) for levofloxacin. For cardiovascular death, the adjusted ORs for azithromycin, moxifloxacin, and levofloxacin were 2.62 (95% CI, 1.69-4.06), 2.31 (95% CI, 1.39-3.84), and 1.77 (95% CI, 1.22-2.59), respectively. No association was noted between clarithromycin or ciprofloxacin and adverse cardiac outcomes. CONCLUSIONS:Healthcare professionals should consider the small but significant increased risk of ventricular arrhythmia and cardiovascular death when prescribing azithromycin and moxifloxacin. Additional research is needed to determine whether the increased risk of mortality is caused by the drugs or related to the severity of infection or the pathogens themselves.
10.1093/cid/ciu914
Use of azithromycin and risk of ventricular arrhythmia.
Trifirò Gianluca,de Ridder Maria,Sultana Janet,Oteri Alessandro,Rijnbeek Peter,Pecchioli Serena,Mazzaglia Giampiero,Bezemer Irene,Garbe Edeltraut,Schink Tania,Poluzzi Elisabetta,Frøslev Trine,Molokhia Mariam,Diemberger Igor,Sturkenboom Miriam C J M
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne
BACKGROUND:There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia. METHODS:We conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders. RESULTS:We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis. INTERPRETATION:Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.
10.1503/cmaj.160355
Electrophysiologic Studies on the Risks and Potential Mechanism Underlying the Proarrhythmic Nature of Azithromycin.
Zhang Mengdan,Xie Ming,Li Sha,Gao Ying,Xue Shuyin,Huang Huili,Chen Kesu,Liu Fuming,Chen Long
Cardiovascular toxicology
The mechanisms underlying arrhythmia induced by the clinical use of azithromycin are poorly understood. We aimed to investigate the proarrhythmic effects of azithromycin using electrocardiogram (ECG) and ion channel models. In vivo and in vitro guinea pig ECG and current and voltage clamp recordings were carried out. Azithromycin at 114.6 mg/kg (three times the clinically relevant dose) reduced heart rate (HR) and prolonged the PR, QRS and rate-corrected QT (QTc) intervals of guinea pig ECG in vivo. In vitro technique revealed that azithromycin at 207.5 and 415 mg/L [five and ten times clinically relevant concentration (CRC)] reduced HR and prolonged the PR, QRS and QTc intervals in the isolated guinea pig heart ECG. Both arrhythmias presented bradyarrhythmic features, mainly with reduced HR and prolonged PR interval. Action potential analysis from the guinea pig cardiomyocytes indicated that azithromycin at 830 mg/L (20 times CRC) significantly prolonged the action potential durations at 50% (APD) and 90% (APD) of full repolarization levels with a rectangular pattern. Azithromycin significantly suppressed the L-type Ca and Na currents from the left ventricular myocytes of guinea pig at 50% inhibiting concentrations (IC) of 942.5 ± 68.4 mg/L (22.7 times CRC) and 1123.0 ± 87.7 mg/L (27.1 times CRC), respectively. However, azithromycin at 50 times CRC (2075 mg/L) inhibited I current at an inhibition rate of 30.99 ± 5.23% with an undetectable IC. Azithromycin caused bradyarrhythmia primarily by inhibiting L-type Ca and Na currents.
10.1007/s12012-017-9401-7
Prevalence of Cardiac Risk Factors in Patients Prescribed Azithromycin before and after the 2012 FDA Warning on the Risk of Potentially Fatal Heart Rhythms.
Patel Haridarshan,Calip Gregory Sampang,DiDomenico Robert J,Schumock Glen T,Suda Katie J,Lee Todd A
Pharmacotherapy
STUDY OBJECTIVE:To measure the prevalence of cardiac risk factors among patients prescribed azithromycin before and after the United States Food and Drug Administration (FDA) issued a warning on May 17, 2012, on the risk of potentially fatal heart rhythms associated with the drug. DESIGN:Retrospective cohort study using administrative claims data. DATA SOURCE:Truven Health Analytics MarketScan database. PATIENTS:A total of 12,971,078 unique patients with 23,749,652 azithromycin prescriptions dispensed between January 2009 and June 2015 were included. Patients had to be continuously enrolled in a health plan for at least 365 days (baseline) before the date of azithromycin dispensing (index date). Cohorts were assigned based on the index dates of the azithromycin prescriptions, either before (January 1, 2009-May 1, 2012) or after (June 1, 2012-June 30, 2015) the FDA warning was issued. MEASUREMENTS AND MAIN RESULTS:A cardiac risk factor included either a cardiac condition (heart failure or dysrhythmias) or concurrent use of drugs that prolong the QT interval. The unit of analysis was each prescription of azithromycin. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the prevalence of cardiac risk factors. Mean age of the patients was 40.1 ± 21.3 years old, with 60.8% females. Prior to the FDA warning, 11,596,022 (48.8%) azithromycin prescriptions were identified, and 12,153,630 (51.2%) were identified after the warning. The prevalence of a preexisting cardiac condition was 7.3% versus 7.9% (p<0.0001) before and after the FDA warning, respectively. Concurrent use of a QT-interval-prolonging drug was 23.3% versus 24.2% (p<0.0001) before and after the FDA warning, respectively. After controlling for confounders, the odds of having a cardiac risk factor after the FDA warning were significantly lower (odds ratio 0.938, 95% CI 0.936-0.940) compared with before the FDA warning. CONCLUSION:Despite the 2012 FDA warning, a nontrivial number of azithromycin prescriptions was prescribed concurrently in patients with preexisting a cardiac condition (1 of 12 azithromycin prescriptions) and in those using a QT-interval-prolonging drug (1 of 5 azithromycin prescriptions). After adjusting for confounders, the odds of cardiac risk factors being present in patients prescribed azithromycin were modestly lower after the warning; however, the prevalence remained essentially unchanged before and after the FDA warning was issued.
10.1002/phar.2355
Possible Azithromycin-Induced Life-Threatening Arrhythmia Requiring Extracorporeal Membrane Oxygenation Support: A Case Report.
Al-Jazairi Abdulrazaq S,Alotaibi Haifa S
The American journal of case reports
BACKGROUND Azithromycin is a commonly prescribed antibiotic due to several advantages, including the broad range of indications, spectrum of activity, favorable drug interaction profile, and convenience of dosing. Although azithromycin carries a black-box warning for QTc prolongation and ventricular arrhythmias, these are considered rare adverse effects. CASE REPORT We present the case of a 37-year-old woman who received azithromycin (500 mg) for follicular tonsillitis and was admitted for worsening of symptoms. On the same day of admission to a secondary hospital, she became unresponsive and had cardiac arrest, for which cardiopulmonary resuscitation (CPR) was performed for 26 min. As per the input from the secondary hospital, she had multiple ventricular tachycardia (VT) and ventricular fibrillation, and needed to be transferred to a tertiary care hospital for further management. Veno-arterial extracorporeal membrane oxygenation (ECMO) support was inserted to support her hemodynamics, and serial ECGs showed significant QT interval prolongation up to 600 msec. The QT prolongation resolved over 10 days and she was successfully weaned-off ECMO. CONCLUSIONS Although azithromycin has a relatively safe profile, it is also associated with life-threatening cardiac arrhythmias that may require surgical intervention to stabilize the patient hemodynamically.
10.12659/AJCR.926951
Risk of cardiac events with azithromycin-A prediction model.
Patel Haridarshan,DiDomenico Robert J,Suda Katie J,Schumock Glen T,Calip Gregory S,Lee Todd A
PloS one
Previous studies have suggested an increased risk of cardiac events with azithromycin, but the predictors of such events are unknown. We sought to develop and validate two prediction models to identify such predictors. We used data from Truven Marketscan Database (01/2009 to 06/2015). Using a split-sample approach, we developed two prediction models, which included baseline demographics, clinical conditions (Model 1), concurrent use of any drug (Model 1) and therapeutic class (Model 2) with a risk of QT-prolongation (CQT-Rx). Patients enrolled in a health plan for 365 days before and five days after dispensing of azithromycin (episodes). Cardiac events included syncope, palpitations, ventricular arrhythmias, cardiac arrest as a primary diagnosis for hospitalization including death. For each model, a backward elimination of predictors using logistic regression was applied to identify predictors in 100 random samples of the training cohort. Predictors prevalent in >50% of the models were included in the final model. A score for the Assessment of Cardiac Risk with Azithromycin (ACRA) was generated using the training cohort then tested in the validation cohort. A cohort of 20,134,659 episodes with 0.03% cardiac events were included. Over 60% included females with mean age of 40.1±21.3 years. Age, sex, history of syncope, cardiac dysrhythmias, non-specific chest pain, and presence of a CQT-Rx were included as predictors for Model-1 (c-statistic = 0.68). For Model-2 (c-statistic = 0.64), predictors included age, sex, anti-arrhythmic agents, anti-emetics, antidepressants, loop diuretics, and ACE inhibitors. ACRA score is available online (bit.ly/ACRA_2020). The ACRA score may help identify patients who are at higher risk of cardiac events following treatment with azithromycin. Providers should assess the risk-benefit of using azithromycin and consider alternative antibiotics among high-risk patients.
10.1371/journal.pone.0240379