Abstract
There are many antibiotics from various chemical classes available in drug armamentarium for the treatment of community-acquired infections at out-patient basis. In such cases safety and tolerability of administered treatment is of no less importance than its efficacy. Recent data suggest that adverse drug reactions associated with the use of antibiotics represent about 20% of all drug-related emergency department visits. This article reviews the most significant adverse drug reactions of antibiotics used for out-patient treatment. Special attention is devoted to those reactions which are commonly underappreciated by general practitioners. Safety information presented in this review may prove to be useful for choosing of the safest antibiotic for an individual patient.
-
1.
Budnitz D.S., Pollock D.A., Weidenbach K.N., et al. National surveillance of emergency department visits for outpatient adverse drug events. JAMA. 2006; 296:1858- 66.
-
2.
Shehab N., Patel P.R., Srinivasan A., Budnitz D.S. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis. 2008; 47:735-43.
-
3.
Lipsky B.A., Baker C.A. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis. 1999; 28:352-64.
-
4.
Stahlmann R., Lode H. Toxicity of quinolones. Drugs. 1999; 58 (suppl 2):37-42.
-
5.
Bartholow M. Top 200 Prescription Drugs of 2009. Pharmacy Times. May 11, 2010. http://www.pharmacytimes.com/issue/pharmacy/2010/May2010/ RxFocusTopDrugs-0510.
-
6.
IMS Health. IMS Health Reports U.S. Prescription Sales Grew 5.1 Percent in 2009, to $300.3 Billion. Press release. IMS Health Web site. April 1, 2010.
-
7.
White A.R., Kaye C., Poupard J., et al. Augmentin (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent. J Antimicrob Chemother. 2004; 53 (Suppl 1):i3- 20.
-
8.
Bigby M., Jick S., Jick H., et al. Drug-induced cutaneous reactions: a report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982. JAMA. 1986; 256:3358-63.
-
9.
Lazarou J., Pomeranz B.H., Corey P.N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998; 279:1200-5.
-
10.
Pirmohamed M., James S., Meakin S., et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients. BMJ. 2004; 329:15-9.
-
11.
Fiszenson-Albala F., Auzerie V., Mahe E., et al. A 6- month prospective survey of cutaneous drug reactions in a hospital setting. Br J Dermatol. 2003; 149:1018-22.
-
12.
Kerr J.R. Penicillin allergy: a study of incidence as reported by patients. Br J Clin Pract. 1994; 48:5-7.
-
13.
Ahlstedt S. Penicillin allergy: can the incidence be reduced? Allergy. 1984; 39:151-64.
-
14.
Lee C.E., Zembower T.R., Fotis M.A., et al. The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance. Arch Intern Med. 2000; 160(18):2819-22.
-
15.
Janeway C., Travers C., Walport M., et al. Immunology: The Immune System in Health and Disease. 5th ed. New York: Garland; 2001.
-
16.
Gruchalla R.S., Pirmohamed M. Clinical practice. Antibiotic allergy. N Engl J Med. 2006; 354(6):601-9.
-
17.
Pirmohamed M., Breckenridge A.M., Kitteringham N.R., et al. Adverse drug reactions. BMJ. 1998; 316:1295-8.
-
18.
Pirmohamed M., Kitteringham N.R., Park B.K. The role of active metabolites in drug toxicity. Drug Saf.1994; 11:114-44.
-
19.
Rudolph A.H., Price E.V. Penicillin reactions among patients in venereal disease clinics: a national survey. JAMA 1973; 223:499-501.
-
20.
Neu H.C., Wilson A.P.R., Gruneberg R.N. Amoxycillin/ Clavulanic Acid: a Review of its Efficacy in over 38,500 Patients from 1979 to 1992. J Chemother 1993; 5:67-93.
-
21.
Thompson J.W., Jacobs R.F. Adverse effects of newer cephalosporins. An update. Drug Saf. 1993; 9:132-42.
-
22.
Norrby S.R. Side Effects of Cephalosporins. Drugs 1995; 34 (Suppl. 2):105-20.
-
23.
Naldi L., Conforti A., Venegoni M., et al. Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions. Br J Clin Pharmacol 1999; 48:839-46.
-
24.
Mockenhaupt M., Schopf E. Progress in Allergy and Clinical Immunology, vol. 4, Cancun (Mexico): Proceedings of the XVIth International Congress of Allergology and Clinical Immunology, Cancun, Mexico, 1997. P. 352-60.
-
25.
Mahboob A., Haroon T.S. Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol 1998; 37:833-8.
-
26.
van der Klauw M.M., Wilson J.H., Stricker B.H. Drugassociated anaphylaxis: 20 years of reporting in The Netherlands (1974-1994) and review of the literature. Clin Exp Allergy 1996; 26:1355-63.
-
27.
Pedersen-Bjergaard U., Andersen M., Hansen P.B. Thrombocytopenia induced by noncytotoxic drugs in Denmark 1968-91. J Intern Med 1996; 239:509-15.
-
28.
Henry D.C., Nenad R.C., Iravani A., et al. Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women. Sparfloxacin Multicenter Uncomplicated Urinary Tract Infection Study Group. Clin Ther 1999; 21:966-81.
-
29.
Araújo L., Demoly P. Macrolides allergy. Curr Pharm Des. 2008; 14(27):.2840-62.
-
30.
Demoly P., Benahmed S., Valembois M., et al. Allergy to macrolide antibiotics. Review of the literature. Presse Med. 2000; 29(6):321-6.
-
31.
Makins R., Ballinger A. Gastrointestinal side effects of drugs. Expert Opin Drug Saf. 2003; 2 (4):421-9.
-
32.
Jaspersen D. Drug-induced oesophageal disorders: pathogenesis, incidence, prevention and management. Drug Saf. 2000; 22 (3):237-49.
-
33.
Nassar N.N., Gregg C.R. Esophageal Infections. Curr Treat Options Gastroenterol. 1998; 1 (1):56-63.
-
34.
Mahon B.E., Rosenman M.B., Kleiman M.B. Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis. J Pediatr. 2001; 139 (3):380-4.
-
35.
Owens R.C.Jr., Ambrose P.G. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis. 2005; 41 (Suppl. 2): S144-57.
-
36.
Salvo F., De Sarro A., Caputi A.P., Polimeni G. Amoxicillin and amoxicillin plus clavulanate: a safety review. Expert Opin Drug Saf. 2009; 8 (1):111-8.
-
37.
Högenauer C., Hammer H.F., Krejs G.J., Reisinger E.C. Mechanisms and management of antibiotic-associated diarrhea. Clin Infect Dis. 1998; 27 (4):702-10.
-
38.
Peeters T.L., Matthys G., Depootere I., et al. Erythromycin is a motilin receptor agonist. Am J Physiol. 1989; 257:470- 74.
-
39.
Caron F., Bouaniche M., Delatour F., et al. B. Effects of two oral erythromycin ethylsuccinate formulations on the motility of the small intestine in human beings. Antimicrob Agents Chemother 1996; 40:1796-800.
-
40.
Bartlett J.G. Antibiotic-associated diarrhea. Clin Infect Dis 1992; 15:573-81.
-
41.
Sgro C., Clinard F., Ouazir K., et al. Incidence of druginduced hepatic injuries: a French population-based study. Hepatology 2002; 36:451-55.
-
42.
Meier Y, Cavallaro M, Roos M, et al. Incidence of druginduced liver injury in medical inpatients. Eur J Clin Pharmacol 2005; 61:135-43.
-
43.
Marschall H.U., Wagner M., Zollner G., Trauner M. Clinical hepatotoxicity. Regulation and treatment with inducers of transport and cofactors. Mol Pharm 2007; 4:895-910.
-
44.
Polson J.E. Hepatotoxicity due to antibiotics. Clin Liver Dis 2007; 11:549-561vi.
-
45.
Saukkonen J.J., Cohn D.L., Jasmer R.M., et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006; 174:935-52.
-
46.
Steele M.A., Burk R.F., DesPrez R.M. Toxic hepatitis with isoniazid and rifampin. A meta-analysis. Chest 1991; 99:465-71.
-
47.
Leitner J.M., Graninger W., Thalhammer F. Hepatotoxicity of antibacterials: pathomechanisms and clinical. Infection. 2010; 38 (1):3-11.
-
48.
Chang C.Y., Schiano T.D. Review article: drug hepatotoxicity. Aliment Pharmacol Ther. 2007; 25 (10):1135-51.
-
49.
Björnsson E. Review article: drug-induced liver injury in clinical practice. Aliment Pharmacol Ther. 2010 Jul;32(1):3-13.
-
50.
De Valle M.B., Av Klinteberg V., Alem N., et al. Druginduced liver injury in a Swedish University hospital out-patient hepatology clinic. Aliment Pharmacol Ther. 2006; 24 (8):1187-95.
-
51.
Andrade R.J., Lucena M.I., Fernandez M.C., et al. Druginduced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005; 129:512-21.
-
52.
Galan M.V., Potts J.A., Silverman A.L., Gordon S.C. The burden of acute nonfulminant drug-induced hepatitis in a United States tertiary referral center [corrected]. J Clin Gastroenterol 2005; 39:64-7.
-
53.
Björnsson E., Jerlstad P., Bergqvist A., Olsson R. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol. 2005; 40 (9):1095-101.
-
54.
de Abajo F.J., Montero D., Madurga M., García Rodríguez L.A. Acute and clinically relevant drug-induced liver injury: a population based case-control study. Br J Clin Pharmacol. 2004; 58 (1):71-80.
-
55.
Russo M.W., Galanko J.A., Shrestha R., et al. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl 2004; 10:1018-23.
-
56.
Larrey D., Vial T., Micaleff A., et al. Hepatitis associated with amoxycillin/clavulanic acid combination report of 15 cases. Gut 1992; 33:368-71.
-
57.
Hussaini S.H., O’Brien C.S., Despott E.J., Dalton H.R. Antibiotic therapy: a major cause of drug-induced jaundice in southwest England. Eur J Gastroenterol Hepatol 2007; 19:15-20.
-
58.
Lucena M.I., Andrade R.J., Fernandez M.C., et al. Determinants of the clinical expression of amoxicillinclavulanate hepatotoxicity: a prospective series from Spain. Hepatology 2006; 44:850-6.
-
59.
Richardet J.P., Mallat A., Zafrani E.S., et al. Prolonged cholestasis with ductopenia after administration of amoxicillin/clavulanic acid. Dig Dis Sci 1999; 44:1997- 2000.
-
60.
Hautekeete M.L., Horsmans Y., Van Waeyenberge C., et al. HLA association of amoxicillin-clavulanate-induced hepatitis. Gastroenterology 1999; 117:1181-6.
-
61.
Gresser U. Amoxicillin-clavulanic acid therapy may be associated with severe side effects – review of the literature. Eur J Med Res 2001; 6:139-49.
-
62.
García Rodríguez L.A., Stricker B.H., Zimmerman H.J. Risk of acute liver injury associated with the combination of amoxicillin and clavulanic acid. Arch Intern Med 1996; 156:1327-32.
-
63.
Salvo F., Polimeni G., Moretti U., et al. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. J Antimicrob Chemother 2007; 60:121-6.
-
64.
Brinker A.D., Wassel R.T., Lyndly J., et al. Telithromycinassociated hepatotoxicity: clinical spectrum and causality assessment of 42 cases. Hepatology 2009; 49:250-7.
-
65.
Ross D.B. The FDA and the case of Ketek. N Engl J Med 2007; 356:1601-4.
-
66.
Sloan B., Scheinfeld N. The use and safety of doxycycline hyclate and other second-generation tetracyclines. Expert Opin Drug Saf. 2008; 7 (5):571-7.
-
67.
Carson J.L., Strom B.L., Duff A., et al. Acute liver disease associated with erythromycins, sulfonamides, and tetracyclines. Ann Intern Med 1993; 119:576-83.
-
68.
Drug Committee of the German Medical Association: hepatotoxicity of fluoroquinolones. Deutsches Ärzteblatt 2002; A 3490.
-
69.
Avelox 400 mg film-coated tablets. Summary of Product Characteristics. http://www.medicines.org.uk/emc/medicine/11841/SPC/Avelox400mgfilm-coatedtablets/.
-
70.
Guo X., Nzerue C. How to prevent, recognize, and treat drug-induced nephrotoxicity. Cleve Clin J Med. 2002; 69 (4):289-90.
-
71.
Abouesh A., Stone C., Hobbs W.R. Antimicrobialinduced mania (antibiomania): a review of spontaneous reports. J Clin Psychopharmacol. 2002; 22 (1):71-81.
-
72.
Meyer F.P., Geller J.C. QT-Intervall-Verlangerung durch Pharmaka. Rardiotoxizitat von Arzneimitteln. Monatsschr Kinderheilkd, 2004.
-
73.
Poluzzi E., Raschi E., Motola D., Moretti U., De Ponti F. Antimicrobials and the risk of torsades de pointes: the contribution from data mining of the US FDA Adverse Event Reporting System. Drug Saf. 2010 Apr 1;33(4):303-14.
-
74.
Simkó J., Csilek A., Karászi J., Lorincz I. Proarrhythmic potential of antimicrobial agents. Infection. 2008 Jun;36(3):194-206.
-
75.
Iannini P. Prolongation of QT interval is probably a class effect of fluoroquinolones. BMJ, 2001; 322:46.
-
76.
Ball P., Mandell L., Niki Y., Tillotson G. Comparative tolerability of the newer fluoroquinolone antibacterials. Drug Saf, 1999; 21:407-21.
-
77.
Ball P. Quinolone induced QT interval prolongation: a not unexpected class effect. J Antimicrob Chemother, 2000; 45:557-9.
-
78.
Conder M.L., Lawrence J.H., Levesque P.C., Blanar M.A. Inhibition of the HERG potassium ion channel by fluoroquinolone antibiotics: correlation with the risk for clinically significant QT interval prolongation (abstr.). Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Ontario, Canada, September 17–20, 2000. Washington, DC : American Society for Microbiology, 2000:474.
-
79.
Ohtani H., Taninaka C., Hanada E., et al. Comparative pharmacodynamic analysis of QT interval prolongation induced by the macrolides clarithromycin, roxithromycin, and azithromycin. Chemotherapy 2000; 44:2630-7.
-
80.
Strle F., Maraspin V. Is azithromycin treatment associated with prolongation of the Q-Tc interval? Wien Klin Wochenschr. 2002; 114(10-11):396-9.
-
81.
Santos N., Oliveira M., Galrinho A., et al. QT interval prolongation and extreme bradycardia after a single dose of azithromycin. Rev Port Cardiol. 2010; 29(1):139-42.
-
82.
Huang B.H., Wu C.H., Hsia C.P., Yin Chen C. Azithromycin-induced torsade de pointes. Pacing Clin Electrophysiol. 2007; 30(12):1579-82.
-
83.
Kezerashvili A., Khattak H., Barsky A., et al. Azithromycin as a cause of QT-interval prolongation and torsade de pointes in the absence of other known precipitating factors. J Interv Card Electrophysiol. 2007; 18(3):243-6.
-
84.
Russo V., Puzio G., Siniscalchi N. Azithromycin-induced QT prolongation in elderly patient. Acta Biomed. 2006; 77(1):30-2.
-
85.
Matsunaga N., Oki Y., Prigollini A. A case of QT-interval prolongation precipitated by azithromycin. N Z Med J. 2003; 116(1185):U666.
-
86.
Tilelli J.A., Smith K.M., Pettignano R. Life-threatening bradyarrhythmia after massive azithromycin overdose. Pharmacotherapy. 2006; 26(1):147-50.
-
87.
Patton W.N., Duffull S.B. Idiosyncratic drug-induced haematological abnormalities. Incidence, pathogenesis, management and avoidance. Drug Saf 1994; 11(6):445-62.
-
88.
Huerta C., García Rodríguez L.A. Risk of clinical blood dyscrasia in a cohort of antibiotic users. Pharmacotherapy. 2002; 22 (5):630-6.
-
89.
Rawson N.S., Harding S.R., Malcom E., Lueck L. Hospitalization for aplastic anemia and agranulocytosis in Saskatchewan: incidence and association with antecedent prescription drug use. J Clin Epidemiol 1998; 51 (12):1343-55.
-
90.
Фокин А.А. Оптимизация мониторинга потребления антимикробных препаратов для системного применения на региональном уровне. Автореф. дисс. канд. мед. наук. Смоленск, 2010. http://www.antibiotic.ru/files/pdf/aref/aref-fokin.pdf
-
91.
Turck D., Bernet J.P., Marx J., et al. Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population. J Pediatr Gastroenterol Nutr. 2003; 37:22-6.
-
92.
Mitropoulos I.F., Rotschafer J.C., Rodvold K.A. Adverse events associated with the use of oral cephalosporins/ cephems. Diagn Microbiol Infect Dis. 2007; 57(suppl 3):67S-76S.
-
93.
Fekety F.R. Safety of parenteral third-generation cephalosporins. Am J Med. 1990; 88:38S-44S.
-
94.
Neu H.C. Third generation cephalosporins: safety profiles after 10 years of clinical use. J Clin Pharmacol. 1990; 30:396-403.
-
95.
Suprax [prescribing information]. Baltimore, MD: Lupin Pharmaceuticals Inc; 2003.
-
96.
Klein J.O. History of macrolide use in pediatrics. Pediatr Infect Dis J. 1997; 16:427-31.
-
97.
Yanagihara K., Izumikawa K., Higa F., et al. Efficacy of azithromycin in the treatment of community-acquired pneumonia, including patients with macrolide-resistant Streptococcus pneumoniae infection. Intern Med. 2009; 48:527-35.
-
98.
Paris R., Confalonieri M., Dal Negro R., et al. Efficacy and safety of azithromycin 1 g once daily for 3 days in the treatment of community-acquired pneumonia: an openlabel randomised comparison with amoxicillin-clavulanate 875/125 mg twice daily for 7 days. J Chemother. 2008; 20:77-86.
-
99.
Kuzman I., Dakovic-Rode O., Oremus M., et al. Clinical efficacy and safety of a short regimen of azithromycin sequential therapy vs standard cefuroxime sequential therapy in the treatment of community-acquired pneumonia: an international, randomized, openlabel study. J Chemother. 2005; 17:636-42.
-
100.
Snyman J.R., Schoeman H.S., Grobusch M.P., et al. Generic versus non-generic formulation of extendedrelease clarithromycin in patients with communityacquired respiratory tract infections: a prospective, randomized, comparative, investigator-blind, multicentre study. Clin Drug Investig. 2009; 29:265-74.
-
101.
Lee P.I., Wu M.H., Huang L.M., et al. An open, randomized, comparative study of clarithromycin and erythromycin in the treatment of children with communityacquired pneumonia. J Microbiol Immunol Infect. 2008; 41:54-61.
-
102.
Bonvehi P., Weber K., Busman T., et al. Comparison of clarithromycin and amoxicillin/clavulanic acid for community-acquired pneumonia in an era of drug-resistant Streptococcus pneumoniae. Clin Drug Investig. 2003; 23:491-501.
-
103.
Tellier G., Niederman M.S., Nusrat R., et al. Clinical and bacteriological efficacy and safety of 5 and 7 day regimens of telithromycin once daily compared with a 10 day regimen of clarithromycin twice daily in patients with mild to moderate communityacquired pneumonia. J Antimicrob Chemother. 2004; 54:515-23.
-
104.
Hopkins S. Clinical toleration and safety of azithromycin. Am J Med. 1991; 91:40S-45S.
-
105.
Whitman M.S., Tunkel A.R. Azithromycin and clarithromycin: overview and comparison with erythromycin. Infect Control Hosp Epidemiol. 1992; 13:357-68.
-
106.
Guay D.R., Patterson D.R., Seipman N., et al. Overview of the tolerability profile of clarithromycin in preclinical and clinical trials. Drug Saf. 1993; 8:350-64.
-
107.
Lode H. Safety and tolerability of commonly prescribed oral antibiotics for the treatment of respiratory tract infections. Am J Med. 2010; 123(4 Suppl):S26-38.
-
108.
Khaliq Y., Zhanel G.G. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis. 2003; 36:1404-10.
-
109.
Graumlich J.F., Habis S., Avelino R.R., et al. Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case-control study. Pharmacotherapy. 2005; 25:1296-302.
-
110.
Park-Wyllie L.Y., Juurlink D.N., Kopp A., et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med. 2006; 354:1352-61.
-
111.
Zambon A., Polo F.H., Contiero P., Corrao G. Effect of macrolide andfluoroquinolone antibacterials on the risk of ventricular arrhythmia and cardiac arrest: an observational study in Italy using case-control, case-crossover and case-time-control designs. Drug Saf. 2009; 32:159-67.
-
112.
Morganroth J., Dimarco J.P., Anzueto A., et al. A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia. Chest. 2005; 128:3398-406.
-
113.
Samaha F.F. QTc interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin. Am J Med. 1999; 107:528-9.
-
114.
Akita M., Shibazaki Y., Izumi M., et al. Comparative assessment of prurifloxacin, sparfloxacin, gatifloxacin and levofloxacin in the rabbit model of proarrhythmia. J Toxicol Sci. 2004; 29:63-71.
-
115.
Schmuck G., Schurmann A., Schluter G. Determination of the excitatory potencies of fluoroquinolones in the central nervous system by an in vitro model. Antimicrob Agents Chemother. 1998; 42:1831-6.