Effect of erythromycin on myocardial repolarization in patients with community-acquired pneumonia

BACKGROUND: Erythromycin has been associated with prolongation of myocardial repolarization and torsades de pointes (TdP). METHODS: To determine the frequency, dose-response, and risk factors for erythromycin-associated prolongation of myocardial repolarization, we observed data of patients admitted to our hospital with pneumonia who were treated with erythromycin. RESULTS: In 35 women and 28 men enrolled in this study, the QTc increased from 434 +/- 4 milliseconds at baseline to 464 +/- 5 milliseconds after receiving a cumulative dose of 3.2 +/- 0.2 g of erythromycin. Neither age, sex, presence of preexistent congestive heart failure/coronary artery disease, electrolyte values, nor cumulative dose of erythromycin was associated with QTc prolongation. In 27 patients who received intravenous erythromycin for 3 days, the QTc increased from 427 +/- 5 milliseconds before to 461 +/- 8 milliseconds at 24 hours but did not increase further by day 3 (457 +/- 10 milliseconds). No patient in this cohort had TdP. CONCLUSIONS: Erythromycin therapy is associated with prolongation of myocardial repolarization that manifests after the first few doses in a majority of patients.     

Electrophysiologic characterization of the antipsychotic drug sertindole in a rabbit heart model of torsade de pointes: low torsadogenic potential despite QT prolongation.

There is growing concern that antipsychotic drugs that prolong the QT interval almost always increase the risk for patients to develop life-threatening ventricular tachyarrhythmias (VTs) of the torsade de pointes type. We therefore sought to compare the electrophysiologic effects of the psychotropic agent sertindole, which prolongs cardiac repolarization by inhibiting the rapid component of the delayed rectifier potassium current (I(Kr)) but has a low torsadogenic potential to the antiarrhythmic agent dl-sotalol. In 18 Langendorff-perfused rabbit hearts, sotalol (10 microM, n = 8) and sertindole (0.5, 1.0, and 1.5 microM; n = 10) led to significant and comparable QT prolongation. In the presence of sotalol, torsade de pointes reproducibly occurred in atrioventricular node-blocked hearts after lowering the potassium concentration to 1.5 mM. High doses of sertindole (1.5 microM) only caused monomorphic VT (n = 4) and nonsustained polymorphic VT (n = 2) in the presence of QRS prolongation. Multiple simultaneous epi- and endocardial monophasic action potentials and a volume-conducted ECG demonstrated widening of the T/U wave, early afterdepolarizations, and increased dispersion of repolarization in the presence of dl-sotalol. In contrast to sotalol, QT and monophasic action potential prolongation were cycle length-independent in the presence of sertindole. Sertindole had no significant effect on transmural or interventricular dispersion of repolarization. Early afterdepolarizations did not occur. Despite comparable QT prolongation, sertindole did not display the proarrhythmic profile typical of other blockers of I(Kr) such as dl-sotalol. It is likely that a different mode of interaction between sertindole and the channel and/or additional pharmacological effects of sertindole, e.g., its ability to inhibit I(Na) and/or its ability to block alpha(1)-receptors, play a role.     

Brady Cardie-Dependent Early Afterdepolarizations in a Patient with QTU Prolongation and Torsade de Pointes in Association with Marked Bradycardia and Hypokalemia

Endocardial monophasic action potentials (MAPs) were recorded at the right ventricular apex in a patient with QTU prolongation and torsade de pointes (TdP) in association with marked bradycardia and hypokalemia. There was a distinct hump on phase 3 repolarization of the MAPs characteristic of early afterdepolarizations (EADs), which was associated with marked prolongation of the QTU interval on the surface electrocardiogram. EAD amplitude was bradycardia dependent, and there was a strong correlation (r = 0.91) between the preceding RR interval and the amplitude of the EAD (percent of MAP amplitude). Intravenous administration of lidocaine or right ventricular pacing suppressed the ventricular premature complexes and TdP in association with the suppression of the EADs on the MAPs. Furthermore, these EADs were not recorded on the MAPs 1 month later when the QTU prolongation and TdP had disappeared. These findings suggest that the TU abnormality and QTU prolongation responsible for TdP were due to bradycardia-dependent EADs.     

Drug-induced arrhythmias

Drug-induced arrhythmias are commonly described as proarrhythmia, arrhythmogenesis or aggravation of arrhythmias. A variety of drugs including cardiotonic drugs (antiarrhythmics, digitalis, cathecholamines), psychiatric drugs(phenothiazines, antidepressants), and macrolide antibiotics would worsen or induce arrhythmias. Among them are bradyarrhythmias and tachyarrhythmias, especially torsade de pointes(TdP) resulting from QT prolongation. There exist some predisposing factors which could potentiate proarrhythmic effect of drugs. They include age, congestive heart failure, ischemic heart disease, renal or hepatic dysfunction, electrolyte disturbance and previous history of proarrhythmia. It should be, therefore, very cautious when drugs with potentially proarrhythmic effect are given to subjects with predisposing factors. Correction of these factors and prevention of bradycardia are important in the management of proarrhythmia and TdP can be treated by infusion of magnesium.     

Comparative in vitro activities of clarithromycin, azithromycin, and erythromycin against Borrelia burgdorferi.

The in vitro activities of the macrolide antibiotics clarithromycin, 14-hydroxy-clarithromycin, azithromycin, and erythromycin against 19 isolates of Borrelia burgdorferi were investigated. MICs ranged from 0.003 to 0.03 microgram of clarithromycin per ml, 0.007 to 0.03 microgram of 14-hydroxyclarithromycin per ml, 0.003 to 0.03 microgram of azithromycin per ml, and 0.007 to 0.06 microgram of erythromycin per ml. Time-kill studies using the B31 strain of B. burgdorferi demonstrated a > or = 3-log10-unit killing after 72 h with each of the macrolide antibiotics tested in concentrations representing twice the respective MICs.     

The new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin.

OBJECTIVE: To review the chemistry, antimicrobial spectrum, pharmacokinetics, clinical trials, adverse effects, and drug interactions of four new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin. DATA SOURCES: Information was obtained from comparative clinical trials, abstracts, conference proceedings, and review articles. Indexing terms included azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, and macrolide antibiotics. STUDY SELECTION: Emphasis was placed on comparative clinical trials involving the new macrolide antibiotics. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were assessed by sample size, macrolide dosage regimen, and therapeutic response. DATA SYNTHESIS: The erythromycins have gained widespread use in treating a variety of infections. Although they are effective, limitations include the need to administer four times a day and the intolerable adverse gastrointestinal effects. Four of the more extensively studied agents, azithromycin, clarithromycin, dirithromycin, and roxithromycin, are currently being studied in patients. Based on the studies to date, the newer macrolides may offer several advantages over erythromycin, including: (1) greater antimicrobial activity against certain organisms; (2) longer elimination half-life, thus allowing less frequent administration; and (3) lower incidence of adverse gastrointestinal effects. CONCLUSIONS: The new macrolide antibiotics appear to offer an improvement over erythromycin. Definitive conclusions about the role of these drugs should await completion of ongoing clinical studies.     

TU Alternans, Long QTU, and Torsade de Pointes: Clinical and Experimental Observations

T or U wave alternans in association with long QTU and torsade de pointes (TdP) is uncommon and its mechanism(s) is unknown. We studied three patients with TU alternans, long QTU, and TdP: patient 1 was a newborn with congenital long QTU; patient 2 had marked hypokalemia and hypomagnesemia; and patient 3 was receiving procainamide. In the three patients, TU alternans was tachycardia dependent and preceded the onset of TdP. In the patient on procainamide, TU alternans and TdP occurred at long cardiac cycles. In this patient, endocardial monophasic action potential (MAP) recordings showed that TU alternans was associated with alternation of the duration of the plateau. A deflection consistent with early afterdepolarization (EAD) arose at a constant time interval from phase 0 but alternated from high and low levels of phase 3. The first ectopic beat of TdP arose on the descending limb of the EAD. TU alternans was investigated by MAP recordings in six normal dogs, following the administration of anthopleurin-A (AP-A), a drug shown to delay sodium inactivation and to induce bradycardia dependent long QTU, EADs, and TdP. In two dogs TU alternans was associated with 2:1 recordings of EAD and nearly constant plateau duration. In three dogs, TU alternans was associated with EAD that occurred in consecutive beats at constant time intervals from phase 0, but alternated from high and low phase 3 because of alternation of the duration of the plateau. In one dog, alternation of EAD and plateau duration occurred. In 36 separate episodes of TdP that were analyzed in the six dogs, 32 were bradycardia dependent but four developed on abrupt shortening of the cardiac cycle associated with alternation of action potential duration. Our results suggest: (1) TU alternans may be due to 2:1 propagation of an EAD or to alternation of the recovery kinetics of a repolarization current; (2) The constant occurrence of EAD in relation to phase 0 in spite of alternation of plateau duration suggests an ionic mechanism synchronized to depolarization; (3) Tachycardia dependent TdP in clinical and experimental examples of long QTU seems to be characteristically associated with TU alternans. Dispersion of repolarization may underlie the increased ventricular electrical instability in these cases.     

Macrolide antibiotics inhibit 50S ribosomal subunit assembly in Bacillus subtilis and Staphylococcus aureus.

Macrolide antibiotics are clinically important antibiotics which are effective inhibitors of protein biosynthesis in bacterial cells. We have recently shown that some of these compounds also inhibit 50S ribosomal subunit formation in Escherichia coli. Now we show that certain macrolides have the same effect in two gram-positive organisms, Bacillus subtilis and Staphylococcus aureus. Assembly in B. subtilis was prevented by erythromycin, clarithromycin, and azithromycin but not by oleandomycin. 50S subunit formation in S. aureus was prevented by each of seven structurally related 14-membered macrolides but not by lincomycin or two streptogramin antibiotics. Erythromycin treatment did not stimulate the breakdown of performed 50S subunits in either organism. The formation of the 30S ribosomal subunit was also unaffected by these compounds. Assembly was also inhibited in a B. subtilis strain carrying a plasmid with the ermC gene that confers macrolide resistance by rRNA methylation. These results suggest that ribosomes contain an additional site for the inhibitory functions of macrolide antibiotics.     

Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics

Quinolones are clinically important antibiotic drugs. One quinolone antibiotic, sparfloxacin (SPX), has been recently reported to increase the QT interval, and another quinolone, grepafloxacin (GRX), was withdrawn because it induced torsade de pointes (TdP), a polymorphic ventricular tachycardia (VT) linked to excessive QT interval prolongation. To determine whether SPX, GRX, and other recently developed quinolones, gatifloxacin (GAT) and moxifloxacin (MOX), have similar, potentially deleterious, properties we compared these agents in two ways. First, we measured their relative antagonist potency against the rapid component of the delayed rectifier K(+) current (I(Kr)), and second we determined the QT interval prolongation and inducibility of VT and TdP using a well established in vivo rabbit arrhythmia model. All of these agents are I(Kr) antagonists with the following IC(50) values (mean +/- S.E.) for I(Kr) block: SPX, 0.23 +/- 0.07 microM; MOX, 0.75 +/- 0.31 microM; GAT, 26.5 +/- 13.4 microM; and GRX, 27.2 +/- 11.6 microM. All agents also increased the maximum QT interval (mean +/- S.E.) from baseline (241 +/- 10 ms): SPX, 370 +/- 30 ms; MOX, 270 +/- 30 ms; GRX, 280 +/- 25 ms; and GAT, 255 +/- 23 ms. No agents caused TdP during a standard 30-min observation period, but SPX-treated animals developed nonsustained VT (three of six) and TdP (one of six) during an extended 60-min observation period. These findings show that I(Kr) block may be a common feature of many quinolone antibiotics, and that the proarrhythmic consequences vary according to I(Kr) antagonist potency, but are also influenced by additional, unidentified factors.     

Evidences of the gender-related differences in cardiac repolarization and the underlying mechanisms in different animal species and human

Clinical and experimental studies have shown that gender differences exist in cardiac repolarization in various animal species and human, as is evidenced by significantly longer QT, JT intervals and action potential duration in females than in males due to a reduced repolarization reserve in females. The latter is shown by the relatively greater increase in ventricular repolarization and higher incidence of torsades de pointes (TdP) in preparations from females by drugs blocking repolarizing K(+) currents. These results can be modulated by gonadectomy, suggesting that gonadal steroids are important determinants of gender difference in repolarization. In human subjects, QT and JT intervals are longer in women, whereas QT dispersion and Tp-e interval (the interval from the peak to the end of T wave) are longer in men. At slow heart rates greater prolongation in QT and increase in transmural repolarization heterogeneity (i.e. increase in Tp-e) may predispose to TdP tachycardias in women. In healthy postmenopausal women, hormone replacement therapy with estrogen alone usually produced a prolongation of QT interval, while estrogen plus progesterone had no significant effects on QT interval but reduced QT dispersion. Along with these, there are still conflicting data reported. Further work is needed before the elucidation of the basis of gender differences in ventricular repolarization.     

Comparative Study of the Effects of Erythromycin and Roxithromycin on Action Potential Duration and Potassium Currents in Canine Purkinje Fibers and Rabbit Myocardium

BACKGROUND: Erythromycin and roxithromycin are macrolide antibiotics in common clinical use. Erythromycin occasionally produces life-threatening arrhythmias (torsades de pointes) by blocking the outward potassium current responsible for repolarization of the cardiac action potential. METHODS AND RESULTS: We used standard cellular electrophysiological and whole-cell patch-clamping techniques to compare the relative efficacy of erythromycin and roxithromycin in prolonging cardiac action potential in canine Purkinje fibers and in blocking individual outward potassium currents in isolated rabbit ventricular myocytes. We demonstrated significant prolongation of action potential duration in canine Purkinje fibers by erythromycin but not roxithromycin at a concentration of 100 μM. The delayed rectifier, the outward potassium current thought to be most sensitive to modulation by drugs, was significantly depressed by both agents at concentrations of >/=30 μM in isolated rabbit ventricular myocytes. Both drugs had similar potencies (26% and 21% reduction by 30 μM erythromycin and roxithromycin, respectively, and 50% and 36% reduction by 100 μM erythromycin and roxithromycin). Neither agent significantly blocked other potassium currents (including the transient outward current). CONCLUSIONS: Taking into account normally observed peak blood concentrations of these agents in clinical use and the fact that roxithromycin is not normally administered intravenously, we conclude that the risk of proarrhythmia during normal clinical use of oral roxithromycin is extremely remote.     

Activities of various macrolide antibiotics against Mycobacterium leprae infection in mice.

We evaluated the activities of several macrolide antibiotics against M. leprae infections in mouse footpads. Erythromycin and azithromycin were inactive, while both roxithromycin and clarithromycin were found to be consistently active and, in fact, bactericidal. By both methods, clarithromycin was found to be superior to roxithromycin, a finding which, at least in part, may be a consequence of the higher levels of clarithromycin at the site of infection.     

Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes

A number of non-cardiovascular drugs have been withdrawn from clinical use due to unacceptable adverse cardiac side-effects involving drug-induced Torsades de Pointes (TdP)--a rare, life-threatening polymorphic ventricular tachycardia associated with prolongation of the action potential duration of ventricular myocytes and, hence, prolongation of the QT interval, of the electrocardiogram (ECG), which measures the total time for activation of the ventricles and their recovery to the resting state. Research has suggested that women are more prone to develop TdP than men during administration of medicines that share the potential to prolong the QT interval, with 65-75% of drug-induced TdP occurring in women. Clinical and experimental studies show that female sex demonstrate differences in the electrocardiographic pattern of ventricular repolarization in human and other animal species and is associated with a longer rate-corrected QT (QTc) interval at baseline than males. Reports of a similar propensity towards drug-induced TdP in both premenopausal and postmenopausal women support factors in addition to those of female sex hormones eliciting sex-based differences in ventricular repolarization. However, conflicting evidence suggests sex hormones may have a role in increasing the susceptibility of women or ultimately reducing the susceptibility of men to TdP. Cyclical variations in hormone levels during the menstrual cycle have been associated with an increased and reduced risk of TdP. In contradiction to this finding, the male sex hormone is thought to be beneficial. Modulation of the ventricular repolarization by testosterone may explain why the QTc interval shortens at puberty, and might account for the tendency towards an age-dependent reduction in the incidence of drug-induced TdP in men. Mechanisms underlying these differences are not fully understood but a case for the involvement of gonadal steroids is obviously strong. Therefore, further non-clinical/clinical investigations ought to be a necessary step to elucidate any sex differences in cardiac repolarization characteristics, QT interval prolongation and susceptibility to cardiac arrhythmias. This may have implications for the development of the safest medicinal products and for the clinical management of cardiac arrhythmias.     

Electrophysiological safety of sertindole in dogs with normal and remodeled hearts

Inhibition of the potassium current IKr and QT prolongation are associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. We investigated the cardiac electrophysiological effects of sertindole, an antipsychotic drug reported to prolong the QT interval in schizophrenic patients. In cell cultures, sertindole seemed to be a selective blocker of IHERG over other ion currents. For IHERG, the IC50 value was 64 +/- 7 nM, whereas ISCN5A, ICa,L, ICa,T, IKCNQ1/KCNE1, and IKv4.3 were blocked in the micromolar range. In canine ventricular myocytes, the IC50 value for IKr inhibition by sertindole was 107 +/- 21 nM. Action potentials in these cells prolonged in a reverse rate- and concentration-dependent manner at 10 to 300 nM sertindole. In vivo, sertindole was administered to anesthetized dogs at clinically relevant (0.05-0.20 mg/kg) and high doses (1.0-2.0 mg/kg) i.v. At 0.05 to 0.20 mg/kg sertindole (plasma concentrations 30-157 nM), QTc was prolonged by 1 to 5% in normal dogs and by 9 to 20% in dogs with remodeled hearts due to chronic atrioventricular block (CAVB). TdP was not induced at these doses in normal dogs or in CAVB dogs with reproducible induction of TdP by dofetilide in previous experiments. At 1.0 to 2.0 mg/kg sertindole (plasma concentrations 0.5-3.1 microM), QTc prolonged by 6 to 11% in normal dogs and by 22% in dofetilide-sensitive CAVB dogs. TdP occurred in three of five animals in the latter group. Thus, at high i.v. doses sertindole can pose a serious proarrhythmic risk when electrical remodeling of the ventricles is present. At clinically relevant doses, however, sertindole does not cause TdP in anesthetized dogs with normal or remodeled hearts.     

Clarithromycin reduces Isus and Ito currents in human atrial myocytes with minor repercussions on action potential duration

The macrolide antibacterial agent clarithromycin has been shown to cause QT interval prolongation on the electrocardiogram. In rabbit heart preparations clarithromycin (concentration dependently) lengthened the action potential duration and blocked the delayed rectifier current. The aim of the present study was to investigate the clarithromycin effects: (i) on the Ca2+ L-type and the main K+ repolarizing currents on human atrial myocytes, using whole-cell patch clamp recordings and (ii) on action potentials recorded from human atrial and ventricular myocardium using conventional microelectrodes. It has been found that (i) 10-30 microM clarithromycin reduced the sustained current Isus significantly and that a 100 microM concentration was needed to cause a significant reduction in the transient outward current Ito, whereas clarithomycin did not affect the calcium current and (ii) clarithromycin (10-100 microM) prolonged the action potential duration in atrial preparations but did not alter the different parameters of the ventricular action potential. It is concluded that clarithromycin exerts direct cardiac electrophysiological effects that may contribute to pro-arrythmic potential.     

Anti-inflammatory activity of macrolide antibiotics

The effect of four macrolide antibiotics (roxithromycin, clarithromycin, erythromycin, and azithromycin) on the generation of some mediators and cytokines involved in the inflammatory process has been studied both in vivo and in vitro. Rat carrageenin pleurisy was used as a model of acute inflammation, and the macrolides were administered (10, 20, and 40 mg/kg p.o.) 1 h before the carrageenin challenge. Exudate volume and leukocyte accumulation were both dose-dependently reduced by roxithromycin, clarithromycin and erythromycin in either normal or adrenalectomized animals. Furthermore, in normal rats, prostaglandin (PG)E(2), nitrate plus nitrite, and tumor necrosis factor-alpha levels in pleural exudate were significantly reduced by these macrolides. Roxithromycin appeared more effective than erythromycin and clarithromycin, whereas azithromycin only slightly affected the inflammatory reaction. None of the macrolides were able to modify leukotriene B(4) exudate levels. In vitro experiments have shown that the four macrolides (5-80 microM) reduced in a concentration-dependent manner the production of 6-keto-PGF(1alpha), NO(2)(-), tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by lipopolysaccharide-stimulated J774 macrophages. In J774 cells, the inhibition of 6-keto-PGF(1alpha) and NO(2)(-) production by roxithromycin and erythromycin was not dependent on direct inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activity because it appears to be related to the inhibition of cyclooxygenase-2 and inducible nitric oxide synthase protein expression. In conclusion, the present study shows that macrolide antibiotics have anti-inflammatory activity, which likely depends on their ability to prevent the production of proinflammatory mediators and cytokines, and suggest that these agents, particularly roxithromycin, can exert therapeutic effects independently of their antibacterial activity.     

Erythromycin shortens neutrophil survival by accelerating apoptosis.

Erythromycin is reported to have an anti-inflammatory action, which may account for its clinical effectiveness in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To evaluate the anti-inflammatory action of erythromycin, we examined the survival of isolated neutrophils with and without erythromycin. Erythromycin shortened neutrophil survival in a dose-dependent fashion, with a maximum effect at 10 micrograms/ml [corrected] and above. Survival at 24 h was 63.4% in medium with 10 micrograms of erythromycin per ml compared with 82.7% in control medium (P < 0.01). This shortening of survival was brought about by acceleration of apoptosis, as evidenced by transmission electron microscopy. In a manner similar to that of erythromycin, other macrolide antibiotics, i.e., clarithromycin, roxithromycin, and midecamycin, also shortened neutrophil survival, but neither the beta-lactams ampicillin and cefazolin nor the aminoglycoside gentamicin affected their survival. Erythromycin increased intracellular levels of cyclic AMP (cAMP) to 150% of control levels in neutrophils. Forskolin, rolipram, and dibutyryl-cAMP, which are known to increase intracellular cAMP levels, also shortened neutrophil survival. H-89, an inhibitor of cAMP-dependent protein kinase A, partially blocked the survival-shortening effect of erythromycin. Our findings suggest that erythromycin shortens neutrophil survival at least in part through elevation of intracellular cAMP levels.     

New macrolide antibiotics: clarithromycin and azithromycin.

Clarithromycin and azithromycin are new semisynthetic macrolide antibiotics structurally related to erythromycin. They are well absorbed and widely distributed, with excellent cellular and tissue penetration. Both have a broader spectrum of activity and fewer gastrointestinal side effects than erythromycin. Currently, clarithromycin and azithromycin are approved by the U.S. Food and Drug Administration for respiratory tract infections and skin infections, but they may also have use in mycobacterial and Toxoplasma infections in patients with acquired immunodeficiency syndrome.     

Phenotypes of macrolide resistance of group A streptococci isolated from outpatients in Bavaria and susceptibility to 16 antibiotics

The purpose of the present study was to determine the antimicrobial resistance among Streptococcus pyogenes in Bavaria, Germany. Five hundred and forty isolates of S. pyogenes were collected from patients with tonsillopharyngitis. Of these, 425 isolates were obtained from children and 115 from adult patients. All isolates were tested for susceptibility to macrolides, clindamycin, penicillin and 10 other commonly prescribed antimicrobial agents, using broth microdilution tests. All isolates were fully susceptible to penicillin, amoxicillin and cephalosporins; 16.1% of the isolates were resistant to tetracycline. MIC(90) values of erythromycin, clarithromycin, azithromycin and josamycin were 16, 4, 16 and 0.5 mg/L. The overall resistance rate of S. pyogenes to erythromycin, clarithromycin and azithromycin was 13.3%. All isolates resistant to erythromycin were also resistant to clarithromycin and azithromycin, and vice versa. Erythromycin resistance rates were higher in adult patients (19.1%) than in children (11.8%). The resistance rate to josamycin was only 1.5%, a value similar to that of clindamycin (1.1%). Among the 72 erythromycin-resistant isolates the M phenotype of macrolide resistance predominated (78%), while percentages of cMLS(B) (8%) and iMLS(B) (14%) phenotypes were low. Of the iMLS(B) strains (n = 10), the majority were of the subtype C (n = 8). The M phenotype was associated with a low, and the iMLS(B)-C phenotype with a high, rate of resistance to tetracycline. Conclusively, present data point to rising macrolide resistance among S. pyogenes in Bavaria.