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Azithromycin
Indications
Azithromycin is a broad-spectrum macrolide antimicrobial and one of the most frequently prescribed antimicrobial drugs in the United States. Azithromycin is an erythromycin derivative with greatly enhanced activity against gram-negative bacteria (including Enterobacteriaceae) that also provides coverage against many gram-positive organisms.[1][2] As an inhibitor of bacterial protein synthesis, azithromycin is effective against many "atypical" bacteria such as chlamydiae (eg, Chlamydia trachomatis and Chlamydophila psittaci), legionella (eg, Legionella pneumophila), mycoplasma (eg, Mycoplasma pneumoniae), and mycobacteria (eg, Mycobacterium avium).[3]
FDA-Approved Indications
- Community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis [4]
- Other upper respiratory infectious processes, including acute otitis media and acute exacerbation of chronic obstructive pulmonary disease (COPD) [5]
- Pharyngitis caused by Streptococcus pyogenes (as an alternative to a β-lactam agent)
- Skin infection due to S pyogenes, Streptococcus agalactiae, or Staphylococcus aureus
- M avium complex (MAC) infection treatment and prophylaxis for patients with advanced AIDS
- Sexually transmitted infections, including chlamydia, gonococcal disease, chancroid (Haemophilus ducreyi), and Mycoplasma genitalium [6][7][8][9][10]
- Urethritis and cervicitis caused by C trachomatis or Neisseria gonorrhoeae. However, the CDC guidelines recommended azithromycin only in combination with gentamicin for uncomplicated gonococcal infections of the cervix or urethra, particularly for patients with a cephalosporin allergy.[11]
Off-Label Uses
- Salmonella typhi infection (enteric fever) [12]
- Long-term prophylaxis for bronchiolitis obliterans (BO) in patients who have undergone lung transplantation [13]
One study examined whether adding azithromycin to standard therapy could induce remission in patients with persistent uncontrolled asthma compared to placebo. Data from 335 participants over 12 months included increased rates of clinical remission and remission with lung function criteria, with some achieving complete remission. Factors such as better asthma-related quality of life predicted clinical remission. These findings suggest that azithromycin may help achieve asthma remission, highlighting its therapeutic potential. However, antimicrobial resistance should be considered.[14]
A systematic review and meta-analysis suggest that azithromycin may reduce hospitalization duration in children with acute bronchiolitis who are younger than 2 years, but it does not prevent the recurrence of wheezing. Further studies with larger sample sizes and clinically relevant outcomes are necessary.[15]
For patients 6 years and older with cystic fibrosis and persistent Pseudomonas aeruginosa infection, the Cystic Fibrosis Foundation recommends the long-term administration of azithromycin to improve lung function and reduce exacerbations. However, due to potential resistance in patients with nontuberculous mycobacterial infections, screening for nontuberculous mycobacteria is advised before initiating azithromycin and every 6 to 12 months thereafter. The committee has determined the benefit of long-term azithromycin therapy to be high for patients with P aeruginosa infection and moderate in those without, with the estimated net benefit deemed small. Meta-analyses indicates that azithromycin therapy for patients with cystic fibrosis yields modest improvements in respiratory function and reduces exacerbation risk, though long-term efficacy is uncertain. Concerns about macrolide resistance highlight the need for further research, especially for patients receiving cystic fibrosis transmembrane conductance regulator modulator therapies.[16][17]
Azithromycin also has efficacy against some protozoal organisms such as Babesia spp. (eg, B microti), Plasmodium spp. (eg, malaria), and Toxoplasma gondii. This medication is sometimes used off-label for the treatment of these parasitic diseases in combination with antiprotozoal drugs such as atovaquone.[18][19][20] According to the Infectious Diseases Society of America (IDSA), atovaquone combined with azithromycin is the preferred antimicrobial regimen for babesiosis.[21][22]
Azithromycin's role in managing viral infections, including respiratory syncytial virus and SARS-CoV-2 has not been determined.[23][24][25][26][27]
Mechanism of Action
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Mechanism of Action
Like other macrolide antimicrobials, azithromycin binds to the 23S portion of the 50S bacterial ribosomal subunit. The drug inhibits bacterial protein synthesis by preventing the transit of aminoacyl-tRNA and the growing protein through the ribosome. Azithromycin is less prone to disassociation from the gram-negative ribosome than erythromycin, which may explain its greater efficacy against gram-negative pathogens.[28] Like other macrolides and protein-synthesis inhibitors, azithromycin is primarily bacteriostatic, inhibiting bacterial growth rather than directly killing organisms. However, higher doses of azithromycin have a bactericidal effect against certain bacteria, such as streptococci and H influenzae.[29][30]
Azithromycin rapidly moves from the bloodstream into tissues and, once there, readily crosses cellular membranes, making it effective against intracellular pathogens.[28][30] In nonbacterial organisms (ie, apicomplexan parasites such as Babesia spp., Plasmodium spp., and Toxoplasma spp.), azithromycin inhibits the 50S ribosome found in the parasite apicoplast, an endosymbiosis-derived organelle with bacteria-like protein-synthesis machinery that performs critical metabolic functions.[31][32]
In addition to azithromycin’s antimicrobial activity, it is a potent immunomodulator that markedly reduces airway neutrophilia, IL-8 gene expression, and C-reactive protein levels in lung transplant recipients and cystic fibrosis.[33][34] Azithromycin has in vitro antiviral properties, which has created interest in the experimental treatment of SARS-CoV-2. By inducing the expression of retinoic acid-inducible gene I (RIG-I) like helicases, azithromycin enhanced the rhinovirus-induced expression of interferons in cultured cells of COPD patients but not in cultured cells of healthy patients in vitro.[35]
Azithromycin resistance mechanisms are primarily linked to mutations in the 23S ribosomal subunit across various bacterial species, including N gonorrhoeae, P aeruginosa, and C trachomatis. In Enterobacteriaceae, resistance is associated with 23S rRNA mutations and ribosomal protein alterations, often coupled with methylation by erm-like genes. Efflux pump overexpression is a common resistance mechanism observed in P aeruginosa, E coli, and S aureus, contributing to reduced drug accumulation.[36]
Pharmacokinetics
Absorption: The absolute bioavailability of a 250 mg dose of azithromycin is approximately 38%. When administered as an oral suspension with food, the peak plasma concentration increases by 56%, while the area under the curve (AUC) remains unchanged.
Distribution: Azithromycin demonstrates excellent tissue penetration and intracellular accumulation. Azithromycin exhibits variable serum protein binding, decreasing from 51% at a concentration of 0.02 µg/mL to 7% at 2 µg/mL. Azithromycin penetrates various human tissues, including the skin, bones, lungs, tonsils, cervix, prostate, ovaries, uterus, stomach, liver, and gallbladder. Azithromycin is highly concentrated in phagocytes, with an intracellular-to-extracellular concentration ratio exceeding 30 after 1 hour. This accumulation in phagocytes likely enhances drug distribution to inflamed tissues.
Metabolism: Azithromycin is metabolized primarily in the liver. After administering single 500 mg oral or intravenous doses of azithromycin, plasma concentrations decrease in a polyphasic manner, leading to an average terminal half-life of about 68 hours.[37] The long half-life and extensive tissue and intracellular distribution permit once-daily dosing and a shorter course of treatment than other antimicrobials. For example, a chlamydia infection may be treated with a single 1 g dose of azithromycin versus 100 mg of doxycycline twice daily for 7 days.
Elimination: Biliary excretion is the primary route for eliminating unchanged medication following oral administration.[38]
Administration
Available Dosage Forms and Strengths
- Oral formulations include tablets (250 mg, 500 mg), packets (1 gram dissolved in ¼ cup or 60 mL of water), and suspension for reconstitution (100 mg/5 mL, 200 mg/5 mL). These formulations can be administered with or without food.
- Intravenous (IV) azithromycin is available in a 500 mg preservative-free solution for reconstitution. IV azithromycin should be infused over at least 60 minutes. Azithromycin should not be administered via intramuscular injection or IV bolus.
- Ophthalmic azithromycin solution (1%) for bacterial conjunctivitis is available in a 2.5 mL bottle.
- The extended-release formulation of azithromycin has been discontinued.
Adult Dosage
The standard dose is 250 or 500 mg, once daily, for 3 to 5 days. Higher doses are typically reserved for severe infections. A single 1 g dose may be given for adults with chlamydia.
Acute otitis media: For patients 6 months and older, azithromycin may be given in a single 30 mg/kg dose, or 10 mg/kg once daily for 3 days, or 10 mg/kg on Day 1, followed by 5 mg/kg/d for the next 4 days.
Community-acquired pneumonia: For patients 6 months and older with an infection due to C pneumoniae, H influenzae, M pneumoniae, or S pneumoniae, the recommended dosage is 10 mg/kg orally as a single dose on Day 1, followed by 5 mg/kg/d orally for the next 4 days. Azithromycin is usually combined with third-generation cephalosporins, such as ceftriaxone.[39]
Acute bacterial sinusitis: The azithromycin dosage is 10 mg/kg orally once daily for 3 days.
Pharyngitis/tonsillitis: For patients 2 years and older with pharyngitis or tonsillitis caused by S pyogenes, azithromycin is given at 12 mg/kg orally once daily for 5 days, with a maximum daily dose of 500 mg.
Specific Patient Populations
Hepatic impairment: The pharmacokinetics of azithromycin in hepatic impairment have not been determined, so it should be prescribed cautiously in this population.
Renal impairment: Azithromycin may be administered to patients with renal disease or failure without regard for creatinine clearance. Dose adjustments are usually not necessary.[37]
Pregnancy considerations: According to the American College of Obstetricians and Gynecologists guidelines, azithromycin may be included in a combination regimen for managing preterm rupture of membranes and can serve as an adjunctive prophylactic antibiotic for patients undergoing emergent cesarean delivery. Additionally, azithromycin may be indicated in specific scenarios before vaginal delivery for patients at high risk of endocarditis.[40][41][42]
Breastfeeding considerations: Azithromycin is concentrated minimally in breast milk, making adverse effects in breastfed infants unlikely; monitoring for gastrointestinal effects, including vomiting, diarrhea, and candidiasis, is recommended. One study demonstrated that a single dose of azithromycin administered to women who were nasal carriers of pathogenic Staphylococcus and Streptococcus during labor reduced bacterial counts in breast milk but increased the prevalence of azithromycin-resistant E coli and K pneumoniae. The use of azithromycin eye drops by breastfeeding mothers poses negligible risk to the infant, and applying pressure over the tear duct for 1 minute after administration can further reduce drug transfer to breast milk.[43]
Pediatric patients: Azithromycin is indicated for patients 6 months or older with community-acquired pneumonia due to C pneumoniae, H influenzae, M pneumoniae, or S pneumoniae. Azithromycin is also FDA-approved for patients 6 months or older with acute otitis media caused by H influenzae, M catarrhalis, or S pneumoniae. Azithromycin is also indicated for patients 6 months or older with acute bacterial sinusitis caused by H influenzae, M catarrhalis, or S pneumoniae. For patients 2 years or older with pharyngitis or tonsillitis caused by S pyogenes, azithromycin is an alternative therapy for individuals who cannot tolerate first-line treatment.
Older patients: No significant differences in safety or effectiveness have been observed between older and younger patients. However, greater sensitivity among some older patients cannot be ruled out based on reported clinical experiences.
Adverse Effects
Azithromycin is considered a safe antimicrobial agent, and only a few patients discontinue it due to adverse effects.[44] This medication is also associated with fewer adverse cardiac effects than other macrolides (eg, erythromycin, clarithromycin).
- Like other macrolides, azithromycin can cause QTc prolongation, which can result in torsades de pointes or polymorphic ventricular tachycardia. In a large retrospective cohort study, azithromycin use correlated with a small but significant absolute increase in cardiovascular death as well as an increased risk of cardiovascular death relative to amoxicillin. These results were most pronounced among patients with the highest baseline cardiovascular risk.[45] However, another large cohort study failed to detect an increased risk of death from cardiovascular causes in young and middle-aged adults.[46]
- Azithromycin is rarely associated with hepatotoxicity, which primarily manifests as hepatocellular injury within 3 weeks of initiating therapy. Clinical features of hepatotoxicity include cholestatic jaundice and elevated transaminase concentrations.[47]
- Like other macrolides, azithromycin is associated with gastrointestinal adverse effects such as nausea and diarrhea. All macrolides exhibit dose-dependent activation of intestinal motilin receptors, stimulating gastric motility. Clinicians widely prescribe erythromycin for treating gastroparesis due to this mechanism.[48]
- Life-threatening hypersensitivity reactions to azithromycin, such as anaphylaxis and Stevens-Johnson syndrome (SJS), are rare.[49][50]
- Macrolides are also associated with the development of Clostridioides difficile infection but to a lesser degree than other common antimicrobial classes (eg, clindamycin, fluoroquinolones, and cephalosporins).[51][52][53]
- A retrospective cohort study found that outpatient azithromycin use was associated with a higher risk of cardiovascular and noncardiovascular death. However, causality cannot be established due to potential residual confounding.[54]
Drug-Drug Interactions
- Azithromycin should be avoided in patients taking the first-generation antipsychotic pimozide. Macrolide antimicrobials inhibit CYP3A4, the same cytochrome that metabolizes pimozide; concomitant use of azithromycin with pimozide can cause dangerous plasma concentrations of pimozide, leading to QTc prolongation and, potentially, lethal arrhythmias. While azithromycin is a poor inhibitor of CYP3A4 relative to other macrolides, avoiding this interaction is still advisable.[55][56]
- Azithromycin is an inhibitor of p-glycoprotein/ABCB1, a cell membrane glycoprotein transporter. Drugs that are substrates of P-glycoprotein, particularly those that are also substrates of CYP3A4, represent a relative contraindication to azithromycin administration. Examples include colchicine and small-molecule calcitonin gene-related peptide (CGRP) antagonists.[57][58]
- Intravesical Bacillus Calmette-Guérin (BCG) instillations are prescribed as a treatment for bladder cancer. While product labeling advises suspending BCG therapy during antibiotic treatment due to potential interference with clinical response, antibiotics may still be necessary during this interval. A recent study of 126 patients found no significant impact of antibiotics on recurrence-free or progression-free survival during BCG induction. Prolonged antibiotic treatment did extend the duration of BCG therapy, but overall, antibiotics did not adversely affect oncological outcomes or adverse effects; a thorough risk-benefit evaluation is required.[59]
Contraindications
Azithromycin is contraindicated for patients with a history of severe hypersensitivity (eg, anaphylaxis or SJS) to azithromycin or another macrolide antimicrobial. Azithromycin is also contraindicated for patients with a history of cholestatic jaundice or hepatic dysfunction related to prior use of the drug.
Warning and Precautions
- Azithromycin effectively preserves FEV and ameliorates bronchiolitis obliterans (BO) with no effect on overall survival in lung transplant patients; however, a study comparing azithromycin with placebo for the prevention of BO in hematopoietic stem cell transplant (HSCT) recipients demonstrated decreased BO-free and overall survival with azithromycin.[60] Hence, long-term azithromycin prophylaxis in HSCT recipients is inadvisable.
- Clinicians should be cautious regarding the concomitant use of azithromycin and other medications that prolong the QTc interval, such as antipsychotics.
- According to the KIDs list (Key Potentially Inappropriate Drugs in Pediatrics), azithromycin should be avoided in neonates due to the risk of hypertrophic pyloric stenosis.[61]
Monitoring
Most courses of treatment with azithromycin are short, and adverse effects requiring therapy adjustment or discontinuation of azithromycin are rare.[44] Azithromycin should be immediately discontinued if signs of hepatotoxicity develop (eg, jaundice or elevated transaminases). For patients receiving long-term azithromycin prophylaxis (eg, AIDS patients for MAC prophylaxis or lung transplant recipients for BO prophylaxis), many patients experience gastrointestinal adverse effects, especially at higher doses (ie, 600 or 1200 mg). Reducing the dose or twice-daily dosing may be considered for these patients.[62][63]
Toxicity
Signs and Symptoms of Overdose
Azithromycin, like other macrolides, is associated with QTc prolongation. Azithromycin administration can result in potentially lethal arrhythmias such as torsades de pointes. This is particularly true for patients with a history of QTc interval perturbation, cardiac arrhythmia, or concomitant use of other medications associated with QTc prolongation. In animal studies, although azithromycin was associated with similar QTc prolongation compared to other macrolides, it seemed to have a negligible proarrhythmic effect.[64] While significant hepatoxicity resulting from azithromycin is relatively rare, macrolides are known to cause mixed hepatocellular/cholestatic drug-induced liver injury. With prompt discontinuation of azithromycin, liver injury is almost always reversible with minimal residual impairment. Often, azithromycin-induced hepatotoxicity has associated immunoallergenic features such as rash, fever, and eosinophilia. Severe reactions, such as anaphylaxis, SJS, and drug reaction with eosinophilia and systemic symptoms (DRESS), are rare.[65] Gastrointestinal toxicity is common but typically mild, and most patients can complete the prescribed course of azithromycin. This toxicity is the result of azithromycin’s activation of pro-motility receptors in the gastrointestinal tract.
Management of Overdose
There is no antidote for azithromycin overdose. General symptomatic and supportive measures should be instituted as necessary.
Enhancing Healthcare Team Outcomes
Although azithromycin is a well-tolerated and effective antimicrobial agent with many clinical indications, it is often inappropriately prescribed, particularly in the primary care setting. Several large retrospective cohort studies involving high levels of inappropriate antimicrobial prescribing overall singled out azithromycin as the most frequently misused drug.[66][67][68][69] Azithromycin is frequently prescribed when there is no clinical indication for antimicrobials, and in many instances, azithromycin is not first-line therapy (e.g., acute otitis media).[66][70] Azithromycin is frequently prescribed when a narrow-spectrum β-lactam (eg, amoxicillin) is the indicated first-line therapy.[66] Increasing resistance to azithromycin, particularly among S pneumoniae isolates, makes the widespread use of azithromycin for upper respiratory illness particularly concerning.[71][72] Broad-spectrum antimicrobial therapy for upper respiratory infection is also associated with increased rates of adverse effects compared with narrow-spectrum agents.[73][74]
One possible association with high rates of azithromycin prescription is patient-reported penicillin allergy.[75] Macrolides, particularly azithromycin, are preferred to β-lactam drugs for many clinical indications. Researchers found 12.8% of patients in an extensive electronic medical records database have a penicillin allergy listed in 1 large cohort.[76] Patients with a reported penicillin allergy are as much as 4 times more likely to be prescribed a macrolide antimicrobial.[75] However, a detailed history of a patient’s adverse reactions to penicillin, paying close attention to features suggestive of IgE-mediated hypersensitivity (eg, urticaria, anaphylaxis), is often sufficient to clarify and possibly remove a listing of penicillin allergy.[77] Patients with more concerning histories may be administered allergy testing or referred to an allergy specialist. Lastly, providers should know the low cross-reactivity rates with cephalosporins (especially third and later-generation agents) and other β-lactams in penicillin allergy.[78]
Through antimicrobial stewardship, healthcare professionals can ensure appropriate antimicrobial administration, including azithromycin. Adhering to evidence-based guidelines and educating patients reduce resistance and optimize treatment outcomes. Clinicians should prescribe azithromycin judiciously and adhere to IDSA guidelines. Clinicians working with or supervising non-physician prescribers should ensure that all prescriptions accord with evidence and guideline-based practice.[68] Additionally, patients requesting antimicrobial therapy when it is not necessary or sharing concerns about drug allergies should be provided with education and appropriate follow-up. Nurses can address patient questions and facilitate continuity of care. Pharmacists are an invaluable resource for helping providers select the most appropriate antimicrobial agent, dosing, and duration of treatment. They can also help providers and patients avoid interactions between azithromycin and other drugs that affect the QTc interval. While azithromycin is a safe and effective antimicrobial drug, practitioners must prescribe it appropriately. The appropriate choice of antibiotic enhances treatment, supports public health, and avoids placing patients at unnecessary risk of adverse effects. An interprofessional team approach and communication among clinicians, pharmacists, and nurses are crucial to decreasing potential adverse effects, improving disease course, and improving outcomes for patients receiving azithromycin.
References
Girard AE, Girard D, English AR, Gootz TD, Cimochowski CR, Faiella JA, Haskell SL, Retsema JA. Pharmacokinetic and in vivo studies with azithromycin (CP-62,993), a new macrolide with an extended half-life and excellent tissue distribution. Antimicrobial agents and chemotherapy. 1987 Dec:31(12):1948-54 [PubMed PMID: 2830841]
Level 3 (low-level) evidenceRetsema J, Girard A, Schelkly W, Manousos M, Anderson M, Bright G, Borovoy R, Brennan L, Mason R. Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against gram-negative organisms. Antimicrobial agents and chemotherapy. 1987 Dec:31(12):1939-47 [PubMed PMID: 2449865]
Bakheit AH, Al-Hadiya BM, Abd-Elgalil AA. Azithromycin. Profiles of drug substances, excipients, and related methodology. 2014:39():1-40. doi: 10.1016/B978-0-12-800173-8.00001-5. Epub [PubMed PMID: 24794904]
Level 3 (low-level) evidenceDekate PS, Mathew JL, Jayashree M, Singhi SC. Acute community acquired pneumonia in emergency room. Indian journal of pediatrics. 2011 Sep:78(9):1127-35. doi: 10.1007/s12098-011-0412-2. Epub 2011 May 4 [PubMed PMID: 21541648]
Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacology & therapeutics. 2014 Aug:143(2):225-45. doi: 10.1016/j.pharmthera.2014.03.003. Epub 2014 Mar 11 [PubMed PMID: 24631273]
Pacifico L, Scopetti F, Ranucci A, Pataracchia M, Savignoni F, Chiesa C. Comparative efficacy and safety of 3-day azithromycin and 10-day penicillin V treatment of group A beta-hemolytic streptococcal pharyngitis in children. Antimicrobial agents and chemotherapy. 1996 Apr:40(4):1005-8 [PubMed PMID: 8849215]
Level 1 (high-level) evidenceAmaya-Tapia G, Aguirre-Avalos G, Andrade-Villanueva J, Peredo-González G, Morfín-Otero R, Esparza-Ahumada S, Rodríguez-Noriega E. Once-daily azithromycin in the treatment of adult skin and skin-structure infections. The Journal of antimicrobial chemotherapy. 1993 Jun:31 Suppl E():129-35 [PubMed PMID: 8396084]
Level 1 (high-level) evidenceDaley CL. Mycobacterium avium Complex Disease. Microbiology spectrum. 2017 Apr:5(2):. doi: 10.1128/microbiolspec.TNMI7-0045-2017. Epub [PubMed PMID: 28429679]
Waugh MA. Azithromycin in gonorrhoea. International journal of STD & AIDS. 1996:7 Suppl 1():2-4 [PubMed PMID: 8652723]
Jensen JS, Cusini M, Gomberg M, Moi H. 2016 European guideline on Mycoplasma genitalium infections. Journal of the European Academy of Dermatology and Venereology : JEADV. 2016 Oct:30(10):1650-1656. doi: 10.1111/jdv.13849. Epub 2016 Aug 9 [PubMed PMID: 27505296]
Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, Reno H, Zenilman JM, Bolan GA. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2021 Jul 23:70(4):1-187. doi: 10.15585/mmwr.rr7004a1. Epub 2021 Jul 23 [PubMed PMID: 34292926]
Carey ME, Dyson ZA, Ingle DJ, Amir A, Aworh MK, Chattaway MA, Chew KL, Crump JA, Feasey NA, Howden BP, Keddy KH, Maes M, Parry CM, Van Puyvelde S, Webb HE, Afolayan AO, Alexander AP, Anandan S, Andrews JR, Ashton PM, Basnyat B, Bavdekar A, Bogoch II, Clemens JD, da Silva KE, De A, de Ligt J, Diaz Guevara PL, Dolecek C, Dutta S, Ehlers MM, Francois Watkins L, Garrett DO, Godbole G, Gordon MA, Greenhill AR, Griffin C, Gupta M, Hendriksen RS, Heyderman RS, Hooda Y, Hormazabal JC, Ikhimiukor OO, Iqbal J, Jacob JJ, Jenkins C, Jinka DR, John J, Kang G, Kanteh A, Kapil A, Karkey A, Kariuki S, Kingsley RA, Koshy RM, Lauer AC, Levine MM, Lingegowda RK, Luby SP, Mackenzie GA, Mashe T, Msefula C, Mutreja A, Nagaraj G, Nagaraj S, Nair S, Naseri TK, Nimarota-Brown S, Njamkepo E, Okeke IN, Perumal SPB, Pollard AJ, Pragasam AK, Qadri F, Qamar FN, Rahman SIA, Rambocus SD, Rasko DA, Ray P, Robins-Browne R, Rongsen-Chandola T, Rutanga JP, Saha SK, Saha S, Saigal K, Sajib MSI, Seidman JC, Shakya J, Shamanna V, Shastri J, Shrestha R, Sia S, Sikorski MJ, Singh A, Smith AM, Tagg KA, Tamrakar D, Tanmoy AM, Thomas M, Thomas MS, Thomsen R, Thomson NR, Tupua S, Vaidya K, Valcanis M, Veeraraghavan B, Weill FX, Wright J, Dougan G, Argimón S, Keane JA, Aanensen DM, Baker S, Holt KE, Global Typhoid Genomics Consortium Group Authorship. Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes. eLife. 2023 Sep 12:12():. doi: 10.7554/eLife.85867. Epub 2023 Sep 12 [PubMed PMID: 37697804]
Level 1 (high-level) evidenceVos R, Vanaudenaerde BM, Verleden SE, De Vleeschauwer SI, Willems-Widyastuti A, Van Raemdonck DE, Schoonis A, Nawrot TS, Dupont LJ, Verleden GM. A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation. The European respiratory journal. 2011 Jan:37(1):164-72. doi: 10.1183/09031936.00068310. Epub 2010 Jun 18 [PubMed PMID: 20562124]
Level 1 (high-level) evidenceThomas D, McDonald VM, Stevens S, Baraket M, Hodge S, James A, Jenkins C, Marks GB, Peters M, Reynolds PN, Upham JW, Yang IA, Gibson PG. Effect of Azithromycin on Asthma Remission in Adults With Persistent Uncontrolled Asthma: A Secondary Analysis of a Randomized, Double-Anonymized, Placebo-Controlled Trial. Chest. 2024 Aug:166(2):262-270. doi: 10.1016/j.chest.2024.02.048. Epub 2024 Feb 29 [PubMed PMID: 38431051]
Level 1 (high-level) evidenceUkkonen RM, Renko M, Kuitunen I. Azithromycin for acute bronchiolitis and wheezing episodes in children - a systematic review with meta-analysis. Pediatric research. 2024 May:95(6):1441-1447. doi: 10.1038/s41390-023-02953-z. Epub 2023 Dec 8 [PubMed PMID: 38066246]
Level 1 (high-level) evidenceSouthern KW, Solis-Moya A, Kurz D, Smith S. Macrolide antibiotics (including azithromycin) for cystic fibrosis. The Cochrane database of systematic reviews. 2024 Feb 27:2(2):CD002203. doi: 10.1002/14651858.CD002203.pub5. Epub 2024 Feb 27 [PubMed PMID: 38411248]
Level 1 (high-level) evidenceMogayzel PJ Jr, Naureckas ET, Robinson KA, Mueller G, Hadjiliadis D, Hoag JB, Lubsch L, Hazle L, Sabadosa K, Marshall B, Pulmonary Clinical Practice Guidelines Committee. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. American journal of respiratory and critical care medicine. 2013 Apr 1:187(7):680-9 [PubMed PMID: 23540878]
Level 1 (high-level) evidenceKrause PJ, Lepore T, Sikand VK, Gadbaw J Jr, Burke G, Telford SR 3rd, Brassard P, Pearl D, Azlanzadeh J, Christianson D, McGrath D, Spielman A. Atovaquone and azithromycin for the treatment of babesiosis. The New England journal of medicine. 2000 Nov 16:343(20):1454-8 [PubMed PMID: 11078770]
Level 3 (low-level) evidenceDunne MW, Singh N, Shukla M, Valecha N, Bhattacharyya PC, Dev V, Patel K, Mohapatra MK, Lakhani J, Benner R, Lele C, Patki K. A multicenter study of azithromycin, alone and in combination with chloroquine, for the treatment of acute uncomplicated Plasmodium falciparum malaria in India. The Journal of infectious diseases. 2005 May 15:191(10):1582-8 [PubMed PMID: 15838784]
Level 1 (high-level) evidenceShiojiri D, Kinai E, Teruya K, Kikuchi Y, Oka S. Combination of Clindamycin and Azithromycin as Alternative Treatment for Toxoplasma gondii Encephalitis. Emerging infectious diseases. 2019 Apr:25(4):841-843. doi: 10.3201/eid2504.181689. Epub [PubMed PMID: 30882331]
. Corrigendum to: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021 Jul 1:73(1):172-173. doi: 10.1093/cid/ciab275. Epub [PubMed PMID: 33960362]
Level 1 (high-level) evidenceKrause PJ, Auwaerter PG, Bannuru RR, Branda JA, Falck-Ytter YT, Lantos PM, Lavergne V, Meissner HC, Osani MC, Rips JG, Sood SK, Vannier E, Vaysbrot EE, Wormser GP. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021 Jan 27:72(2):e49-e64. doi: 10.1093/cid/ciaa1216. Epub [PubMed PMID: 33252652]
Level 1 (high-level) evidenceGautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International journal of antimicrobial agents. 2020 Jul:56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20 [PubMed PMID: 32205204]
Level 2 (mid-level) evidenceGautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Sevestre J, Mailhe M, Doudier B, Aubry C, Amrane S, Seng P, Hocquart M, Eldin C, Finance J, Vieira VE, Tissot-Dupont HT, Honoré S, Stein A, Million M, Colson P, La Scola B, Veit V, Jacquier A, Deharo JC, Drancourt M, Fournier PE, Rolain JM, Brouqui P, Raoult D. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel medicine and infectious disease. 2020 Mar-Apr:34():101663. doi: 10.1016/j.tmaid.2020.101663. Epub 2020 Apr 11 [PubMed PMID: 32289548]
Level 2 (mid-level) evidenceArabi YM, Deeb AM, Al-Hameed F, Mandourah Y, Almekhlafi GA, Sindi AA, Al-Omari A, Shalhoub S, Mady A, Alraddadi B, Almotairi A, Al Khatib K, Abdulmomen A, Qushmaq I, Solaiman O, Al-Aithan AM, Al-Raddadi R, Ragab A, Al Harthy A, Kharaba A, Jose J, Dabbagh T, Fowler RA, Balkhy HH, Merson L, Hayden FG, Saudi Critical Care Trials group. Macrolides in critically ill patients with Middle East Respiratory Syndrome. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2019 Apr:81():184-190. doi: 10.1016/j.ijid.2019.01.041. Epub 2019 Jan 25 [PubMed PMID: 30690213]
Pinto LA, Pitrez PM, Luisi F, de Mello PP, Gerhardt M, Ferlini R, Barbosa DC, Daros I, Jones MH, Stein RT, Marostica PJ. Azithromycin therapy in hospitalized infants with acute bronchiolitis is not associated with better clinical outcomes: a randomized, double-blinded, and placebo-controlled clinical trial. The Journal of pediatrics. 2012 Dec:161(6):1104-8. doi: 10.1016/j.jpeds.2012.05.053. Epub 2012 Jun 28 [PubMed PMID: 22748516]
Level 1 (high-level) evidenceEcheverría-Esnal D, Martin-Ontiyuelo C, Navarrete-Rouco ME, De-Antonio Cuscó M, Ferrández O, Horcajada JP, Grau S. Azithromycin in the treatment of COVID-19: a review. Expert review of anti-infective therapy. 2021 Feb:19(2):147-163. doi: 10.1080/14787210.2020.1813024. Epub 2020 Oct 6 [PubMed PMID: 32853038]
Goldman RC, Fesik SW, Doran CC. Role of protonated and neutral forms of macrolides in binding to ribosomes from gram-positive and gram-negative bacteria. Antimicrobial agents and chemotherapy. 1990 Mar:34(3):426-31 [PubMed PMID: 2159256]
Jelić D, Antolović R. From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials. Antibiotics (Basel, Switzerland). 2016 Sep 1:5(3):. doi: 10.3390/antibiotics5030029. Epub 2016 Sep 1 [PubMed PMID: 27598215]
Neu HC. Clinical microbiology of azithromycin. The American journal of medicine. 1991 Sep 12:91(3A):12S-18S [PubMed PMID: 1656736]
Level 3 (low-level) evidenceSidhu AB, Sun Q, Nkrumah LJ, Dunne MW, Sacchettini JC, Fidock DA. In vitro efficacy, resistance selection, and structural modeling studies implicate the malarial parasite apicoplast as the target of azithromycin. The Journal of biological chemistry. 2007 Jan 26:282(4):2494-504 [PubMed PMID: 17110371]
Level 3 (low-level) evidenceBiddau M, Sheiner L. Targeting the apicoplast in malaria. Biochemical Society transactions. 2019 Aug 30:47(4):973-983. doi: 10.1042/BST20170563. Epub 2019 Aug 5 [PubMed PMID: 31383817]
Verleden GM, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE. Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. American journal of respiratory and critical care medicine. 2006 Sep 1:174(5):566-70 [PubMed PMID: 16741151]
Tarique AA, Tuladhar N, Kelk D, Begum N, Lucas RM, Luo L, Stow JL, Wainwright CE, Bell SC, Sly PD, Fantino E. Azithromycin Augments Bacterial Uptake and Anti-Inflammatory Macrophage Polarization in Cystic Fibrosis. Cells. 2024 Jan 16:13(2):. doi: 10.3390/cells13020166. Epub 2024 Jan 16 [PubMed PMID: 38247856]
Menzel M, Akbarshahi H, Bjermer L, Uller L. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients. Scientific reports. 2016 Jun 28:6():28698. doi: 10.1038/srep28698. Epub 2016 Jun 28 [PubMed PMID: 27350308]
Heidary M, Ebrahimi Samangani A, Kargari A, Kiani Nejad A, Yashmi I, Motahar M, Taki E, Khoshnood S. Mechanism of action, resistance, synergism, and clinical implications of azithromycin. Journal of clinical laboratory analysis. 2022 Jun:36(6):e24427. doi: 10.1002/jcla.24427. Epub 2022 Apr 21 [PubMed PMID: 35447019]
Höffler D, Koeppe P, Paeske B. Pharmacokinetics of azithromycin in normal and impaired renal function. Infection. 1995 Nov-Dec:23(6):356-61 [PubMed PMID: 8655206]
Drew RH, Gallis HA. Azithromycin--spectrum of activity, pharmacokinetics, and clinical applications. Pharmacotherapy. 1992:12(3):161-73 [PubMed PMID: 1319048]
Vaughn VM, Dickson RP, Horowitz JK, Flanders SA. Community-Acquired Pneumonia: A Review. JAMA. 2024 Oct 15:332(15):1282-1295. doi: 10.1001/jama.2024.14796. Epub [PubMed PMID: 39283629]
Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 199: Use of Prophylactic Antibiotics in Labor and Delivery. Obstetrics and gynecology. 2018 Sep:132(3):e103-e119. doi: 10.1097/AOG.0000000000002833. Epub [PubMed PMID: 30134425]
. ACOG Practice Bulletin No. 135: Second-trimester abortion. Obstetrics and gynecology. 2013 Jun:121(6):1394-1406. doi: 10.1097/01.AOG.0000431056.79334.cc. Epub [PubMed PMID: 23812485]
. Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstetrics and gynecology. 2020 Mar:135(3):e80-e97. doi: 10.1097/AOG.0000000000003700. Epub [PubMed PMID: 32080050]
. Azithromycin. Drugs and Lactation Database (LactMed®). 2006:(): [PubMed PMID: 30000259]
Ioannidis JP, Contopoulos-Ioannidis DG, Chew P, Lau J. Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for upper respiratory tract infections. The Journal of antimicrobial chemotherapy. 2001 Nov:48(5):677-89 [PubMed PMID: 11679557]
Level 1 (high-level) evidenceRay WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. The New England journal of medicine. 2012 May 17:366(20):1881-90. doi: 10.1056/NEJMoa1003833. Epub [PubMed PMID: 22591294]
Level 2 (mid-level) evidenceSvanström H, Pasternak B, Hviid A. Use of azithromycin and death from cardiovascular causes. The New England journal of medicine. 2013 May 2:368(18):1704-12. doi: 10.1056/NEJMoa1300799. Epub [PubMed PMID: 23635050]
Level 2 (mid-level) evidenceMartinez MA, Vuppalanchi R, Fontana RJ, Stolz A, Kleiner DE, Hayashi PH, Gu J, Hoofnagle JH, Chalasani N. Clinical and histologic features of azithromycin-induced liver injury. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2015 Feb:13(2):369-376.e3. doi: 10.1016/j.cgh.2014.07.054. Epub 2014 Aug 9 [PubMed PMID: 25111234]
Barboza JL, Okun MS, Moshiree B. The treatment of gastroparesis, constipation and small intestinal bacterial overgrowth syndrome in patients with Parkinson's disease. Expert opinion on pharmacotherapy. 2015:16(16):2449-64. doi: 10.1517/14656566.2015.1086747. Epub 2015 Sep 16 [PubMed PMID: 26374094]
Level 3 (low-level) evidenceNappe TM, Goren-Garcia SL, Jacoby JL. Stevens-Johnson syndrome after treatment with azithromycin: an uncommon culprit. The American journal of emergency medicine. 2016 Mar:34(3):676.e1-3. doi: 10.1016/j.ajem.2015.06.039. Epub 2015 Jun 19 [PubMed PMID: 26194400]
Mori F, Pecorari L, Pantano S, Rossi ME, Pucci N, De Martino M, Novembre E. Azithromycin anaphylaxis in children. International journal of immunopathology and pharmacology. 2014 Jan-Mar:27(1):121-6 [PubMed PMID: 24674687]
Level 3 (low-level) evidenceDial S, Kezouh A, Dascal A, Barkun A, Suissa S. Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2008 Oct 7:179(8):767-72. doi: 10.1503/cmaj.071812. Epub [PubMed PMID: 18838451]
Level 2 (mid-level) evidenceKuntz JL, Chrischilles EA, Pendergast JF, Herwaldt LA, Polgreen PM. Incidence of and risk factors for community-associated Clostridium difficile infection: a nested case-control study. BMC infectious diseases. 2011 Jul 15:11():194. doi: 10.1186/1471-2334-11-194. Epub 2011 Jul 15 [PubMed PMID: 21762504]
Level 2 (mid-level) evidenceDeshpande A, Pasupuleti V, Thota P, Pant C, Rolston DD, Sferra TJ, Hernandez AV, Donskey CJ. Community-associated Clostridium difficile infection and antibiotics: a meta-analysis. The Journal of antimicrobial chemotherapy. 2013 Sep:68(9):1951-61. doi: 10.1093/jac/dkt129. Epub 2013 Apr 25 [PubMed PMID: 23620467]
Level 1 (high-level) evidenceZaroff JG, Cheetham TC, Palmetto N, Almers L, Quesenberry C, Schneider J, Gatto N, Corley DA. Association of Azithromycin Use With Cardiovascular Mortality. JAMA network open. 2020 Jun 1:3(6):e208199. doi: 10.1001/jamanetworkopen.2020.8199. Epub 2020 Jun 1 [PubMed PMID: 32585019]
Westphal JF. Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. British journal of clinical pharmacology. 2000 Oct:50(4):285-95 [PubMed PMID: 11012550]
Flockhart DA, Drici MD, Kerbusch T, Soukhova N, Richard E, Pearle PL, Mahal SK, Babb VJ. Studies on the mechanism of a fatal clarithromycin-pimozide interaction in a patient with Tourette syndrome. Journal of clinical psychopharmacology. 2000 Jun:20(3):317-24 [PubMed PMID: 10831018]
Level 3 (low-level) evidenceBouquié R, Deslandes G, Renaud C, Dailly E, Haloun A, Jolliet P. Colchicine-induced rhabdomyolysis in a heart/lung transplant patient with concurrent use of cyclosporin, pravastatin, and azithromycin. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases. 2011 Jan:17(1):28-30. doi: 10.1097/RHU.0b013e3182056042. Epub [PubMed PMID: 21169852]
Level 3 (low-level) evidenceTerkeltaub RA, Furst DE, Digiacinto JL, Kook KA, Davis MW. Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors. Arthritis and rheumatism. 2011 Aug:63(8):2226-37. doi: 10.1002/art.30389. Epub [PubMed PMID: 21480191]
Aubert C, Culty T, Zidane M, Bigot P, Lebdai S. Antibiotic therapy impact on intravesical BCG therapy efficacy for high-risk localized bladder cancer treatment. Frontiers in oncology. 2023:13():1240378. doi: 10.3389/fonc.2023.1240378. Epub 2024 Mar 8 [PubMed PMID: 38525411]
Bergeron A, Chevret S, Granata A, Chevallier P, Vincent L, Huynh A, Tabrizi R, Labussiere-Wallet H, Bernard M, Chantepie S, Bay JO, Thiebaut-Bertrand A, Thepot S, Contentin N, Fornecker LM, Maillard N, Risso K, Berceanu A, Blaise D, Peffault de La Tour R, Chien JW, Coiteux V, Socié G, ALLOZITHRO Study Investigators. Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial. JAMA. 2017 Aug 8:318(6):557-566. doi: 10.1001/jama.2017.9938. Epub [PubMed PMID: 28787506]
Level 1 (high-level) evidenceMeyers RS, Thackray J, Matson KL, McPherson C, Lubsch L, Hellinga RC, Hoff DS. Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG. 2020:25(3):175-191. doi: 10.5863/1551-6776-25.3.175. Epub [PubMed PMID: 32265601]
Brown BA, Griffith DE, Girard W, Levin J, Wallace RJ Jr. Relationship of adverse events to serum drug levels in patients receiving high-dose azithromycin for mycobacterial lung disease. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1997 May:24(5):958-64 [PubMed PMID: 9142801]
Koletar SL, Berry AJ, Cynamon MH, Jacobson J, Currier JS, MacGregor RR, Dunne MW, Williams DJ. Azithromycin as treatment for disseminated Mycobacterium avium complex in AIDS patients. Antimicrobial agents and chemotherapy. 1999 Dec:43(12):2869-72 [PubMed PMID: 10582873]
Level 1 (high-level) evidenceMilberg P, Eckardt L, Bruns HJ, Biertz J, Ramtin S, Reinsch N, Fleischer D, Kirchhof P, Fabritz L, Breithardt G, Haverkamp W. Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes. The Journal of pharmacology and experimental therapeutics. 2002 Oct:303(1):218-25 [PubMed PMID: 12235254]
Level 3 (low-level) evidenceHoofnagle JH, Björnsson ES. Drug-Induced Liver Injury - Types and Phenotypes. The New England journal of medicine. 2019 Jul 18:381(3):264-273. doi: 10.1056/NEJMra1816149. Epub [PubMed PMID: 31314970]
Fleming-Dutra KE, Demirjian A, Bartoces M, Roberts RM, Taylor TH Jr, Hicks LA. Variations in Antibiotic and Azithromycin Prescribing for Children by Geography and Specialty-United States, 2013. The Pediatric infectious disease journal. 2018 Jan:37(1):52-58. doi: 10.1097/INF.0000000000001708. Epub [PubMed PMID: 28746259]
Chua KP, Fischer MA, Linder JA. Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study. BMJ (Clinical research ed.). 2019 Jan 16:364():k5092. doi: 10.1136/bmj.k5092. Epub 2019 Jan 16 [PubMed PMID: 30651273]
Shively NR, Buehrle DJ, Clancy CJ, Decker BK. Prevalence of Inappropriate Antibiotic Prescribing in Primary Care Clinics within a Veterans Affairs Health Care System. Antimicrobial agents and chemotherapy. 2018 Aug:62(8):. doi: 10.1128/AAC.00337-18. Epub 2018 Jul 27 [PubMed PMID: 29967028]
White AT, Clark CM, Sellick JA, Mergenhagen KA. Antibiotic stewardship targets in the outpatient setting. American journal of infection control. 2019 Aug:47(8):858-863. doi: 10.1016/j.ajic.2019.01.027. Epub 2019 Mar 9 [PubMed PMID: 30862373]
Havers FP, Hicks LA, Chung JR, Gaglani M, Murthy K, Zimmerman RK, Jackson LA, Petrie JG, McLean HQ, Nowalk MP, Jackson ML, Monto AS, Belongia EA, Flannery B, Fry AM. Outpatient Antibiotic Prescribing for Acute Respiratory Infections During Influenza Seasons. JAMA network open. 2018 Jun 1:1(2):e180243. doi: 10.1001/jamanetworkopen.2018.0243. Epub 2018 Jun 1 [PubMed PMID: 30646067]
Critchley IA, Jacobs MR, Brown SD, Traczewski MM, Tillotson GS, Janjic N. Prevalence of serotype 19A Streptococcus pneumoniae among isolates from U.S. children in 2005-2006 and activity of faropenem. Antimicrobial agents and chemotherapy. 2008 Jul:52(7):2639-43. doi: 10.1128/AAC.00310-08. Epub 2008 Apr 28 [PubMed PMID: 18443117]
Karlowsky JA, Thornsberry C, Critchley IA, Jones ME, Evangelista AT, Noel GJ, Sahm DF. Susceptibilities to levofloxacin in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis clinical isolates from children: results from 2000-2001 and 2001-2002 TRUST studies in the United States. Antimicrobial agents and chemotherapy. 2003 Jun:47(6):1790-7 [PubMed PMID: 12760850]
Gerber JS, Ross RK, Bryan M, Localio AR, Szymczak JE, Wasserman R, Barkman D, Odeniyi F, Conaboy K, Bell L, Zaoutis TE, Fiks AG. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections. JAMA. 2017 Dec 19:318(23):2325-2336. doi: 10.1001/jama.2017.18715. Epub [PubMed PMID: 29260224]
Level 2 (mid-level) evidencePai L, Patil S, Liu S, Wen F. A growing battlefield in the war against biofilm-induced antimicrobial resistance: insights from reviews on antibiotic resistance. Frontiers in cellular and infection microbiology. 2023:13():1327069. doi: 10.3389/fcimb.2023.1327069. Epub 2023 Dec 19 [PubMed PMID: 38188636]
Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK. Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ (Clinical research ed.). 2018 Jun 27:361():k2400. doi: 10.1136/bmj.k2400. Epub 2018 Jun 27 [PubMed PMID: 29950489]
Zhou L, Dhopeshwarkar N, Blumenthal KG, Goss F, Topaz M, Slight SP, Bates DW. Drug allergies documented in electronic health records of a large healthcare system. Allergy. 2016 Sep:71(9):1305-13. doi: 10.1111/all.12881. Epub 2016 Apr 6 [PubMed PMID: 26970431]
Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019 Jan 15:321(2):188-199. doi: 10.1001/jama.2018.19283. Epub [PubMed PMID: 30644987]
Romano A, Valluzzi RL, Caruso C, Maggioletti M, Quaratino D, Gaeta F. Cross-Reactivity and Tolerability of Cephalosporins in Patients with IgE-Mediated Hypersensitivity to Penicillins. The journal of allergy and clinical immunology. In practice. 2018 Sep-Oct:6(5):1662-1672. doi: 10.1016/j.jaip.2018.01.020. Epub 2018 Feb 3 [PubMed PMID: 29408440]