zithromax and Pneumococcal-Infections

Mass azithromycin distribution is a core component of trachoma control programmes and could reduce mortality in children younger than 5 years in some settings. In this systematic review we synthesise evidence on the emergence of antimicrobial resistance after mass azithromycin distribution. We searched electronic databases for publications up to June 14, 2018. We included studies of any type (excluding modelling studies, surveillance reports, and review articles) on community-wide distribution of oral azithromycin for the prevention and treatment of trachoma that assessed macrolide resistance, without restrictions to the type of organism. We extracted prevalence of resistance from published reports and requested unpublished data from authors of included studies. Of 213 identified studies, 19 met inclusion criteria (12 assessed Streptococcus pneumoniae) and were used for qualitative synthesis. Macrolide resistance after azithromycin distribution was reported in three of the five organisms studied. The lack of resistance in Chlamydia trachomatis suggests that azithromycin might remain effective for trachoma programmes, but evidence is scarce. As mass azithromycin distribution for trachoma continues and is considered for other indications, ongoing monitoring of antimicrobial resistance will be required.

Topics: Administration, Oral; Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Chlamydia trachomatis; Drug Resistance, Bacterial; Female; Humans; Infant; Macrolides; Male; Pneumococcal Infections; Prevalence; Streptococcus pneumoniae; Trachoma; Treatment Outcome

Antimicrobial agents in the macrolide family have long been considered drugs of potential utility in the management of infections caused by Streptococcus pneumoniae. However, with the emergence of macrolide resistance, the clinical value of macrolides in pneumococcal infections is threatened. In part, as a consequence of the development of macrolide resistance, recently the first agent in the ketolide antimicrobial class, telithromycin, was developed and introduced into clinical practice. The ketolides are macrolide antimicrobials whose chemistry has been modified so as avoid the effects of the most common mechanisms of macrolide resistance with S pneumoniae. This discussion reviews the current state of resistance to macrolides and ketolides with S pneumoniae in North America.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Clarithromycin; Drug Resistance, Bacterial; Humans; Ketolides; Macrolides; Membrane Proteins; Pneumococcal Infections; Streptococcus pneumoniae

To determine whether treatment failures occurred more commonly with azithromycin than with beta-lactam antibiotics in children who developed invasive pneumococcal disease within 30 days of receiving prior antimicrobial therapy.. Retrospective review of medical records of children evaluated at Texas Children's Hospital between 1996 and 2002 who had received antimicrobials (azithromycin or a beta-lactam antibiotic) and developed invasive pneumococcal disease within 30 days. Treatment failure was defined as invasive pneumococcal infection that occurred while taking antimicrobials or within 3 days of stopping azithromycin treatment or 1 day of stopping beta-lactam treatment. Penicillin and azithromycin susceptibilities were determined and categorized according to National Committee for Clinical Laboratory Standards guidelines.. We identified 21 and 33 children with similar demographic features who had developed invasive pneumococcal disease within 1 month of receiving azithromycin or a beta-lactam antibiotic, respectively. Eleven (52%) children in the azithromycin group and 11 (33%) in the beta-lactam group met the definition for treatment failures (P = 0.34). Eight treatment failures while receiving azithromycin were caused by pneumococci with the macrolide-resistant (M) phenotype, 2 with the macrolide-, lincosamide- and streptogramin B-resistant (MLSB) phenotype and 1 by a macrolide-susceptible organism. In the beta-lactam group 7 had a penicillin-resistant isolate, 3 had an intermediately susceptible isolate and 1 had a susceptible isolate.. Our study suggests that treatment failures among patients who developed invasive disease within 30 days of receiving an antimicrobial occur as frequently in patients who receive beta-lactam antibiotics as in those who receive azithromycin. Furthermore macrolide resistant organisms are not more likely to be recovered after a macrolide treatment failure than a penicillin-nonsusceptible isolate being recovered after a beta-lactam treatment failure (P = 1.0).

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactams; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Prospective Studies; Streptococcus pneumoniae; Treatment Failure

The rapid emergence of resistance to antimicrobial agents by Streptococcus pneumoniae in the United States has been influenced by various factors, including the clonal nature of most resistant strains and the fact that organisms with a multiresistant phenotype have become stably endemic. The ease with which transmission occurs and the fact that humans, especially children, are often colonized asymptomatically in the upper respiratory tract have contributed to the problem. Clearly, the most important factor in the emergence of antimicrobial resistance with S. pneumoniae, however, is the selective pressure of antimicrobial agents. Potency, defined as a product of both antibacterial effect and drug delivery, is a key factor. Generally speaking, the more potent an antimicrobial agent, the less likely it is to select for resistance. This is germane to comparisons of oral agents within specific antimicrobial classes (e.g., beta-lactams, macrolides, and fluoroquinolones). Within each class, potencies differ. In view of the existence of stably endemic multidrug-resistant S. pneumoniae, given comparable cost, side-effect profile, palatability, convenience of dosing, and accessibility, use of the most potent agent(s) within a particular class is advocated.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; beta-Lactam Resistance; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Pneumococcal Infections; Streptococcus pneumoniae; United States

We evaluated antibiotic resistance selection in Streptococcus pneumoniae isolates from children participating in an individually randomized trial of single-dose azithromycin versus placebo. After 14 days, the prevalence of resistance to erythromycin, oxacillin, and clindamycin was elevated in the azithromycin versus placebo group. There was no difference at 6 months.

Topics: Anti-Bacterial Agents; Azithromycin; Carrier State; Child; Clindamycin; Drug Resistance, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Nasopharynx; Pneumococcal Infections; Streptococcus pneumoniae

We have recently completed a proof-of-concept trial showing that bacterial colonization decreased in women and newborns after the administration of azithromycin during labor. Here, we aim to assess the effect of the intervention on maternal and neonatal clinical infections.. This was a double-blind, placebo-controlled randomized trial. Gambian women in labor were given either an oral dose of azithromycin (2 g) or placebo. Follow-up was conducted for 8 weeks after delivery.. From April 2013 to April 2014, we recruited 829 mothers and their 830 newborns. Sixteen infants died during the follow-up period (8 per arm). No maternal deaths or serious adverse events related to the intervention were reported. Maternal infections were lower in the azithromycin group (3.6% vs 9.2%; relative risk [RR], 0.40; 95% confidence interval [CI], 0.22-0.71; P = .002), as was the prevalence of mastitis (1.4% vs 5.1%; RR, 0.29; 95% CI, 0.12-0.70; P = .005) and fever (1.9% vs 5.8%; RR, 0.33; 95% CI, 0.15-0.74; P = .006). Among newborns, the overall prevalence of infections was also lower in the azithromycin group (18.1% vs 23.8%; RR, 0.76; 95% CI, 0.58-0.99; P = .052) and there was a marked difference in prevalence of skin infections (3.1% vs 6.4%; RR, 0.49; 95% CI, 0.25-0.93; P = .034).. Azithromycin given to women in labor decreases infections in both women and newborns during the puerperal period. Larger studies designed to evaluate the effect of the intervention on severe morbidity and mortality are warranted.

Topics: Administration, Oral; Azithromycin; Bacterial Infections; Carrier State; Developing Countries; Double-Blind Method; Female; Fever of Unknown Origin; Gambia; Humans; Infant, Newborn; Infant, Newborn, Diseases; Mastitis; Pneumococcal Infections; Pregnancy; Puerperal Infection; Skin Diseases, Bacterial; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus agalactiae

Twenty-four Ethiopian communities were randomized to receive either (1) quarterly mass azithromycin distributions for trachoma for 1 year or (2) delayed treatment. Nasopharyngeal swabs collected from separate cross-sectional population-based samples of children were processed for Streptococcus pneumoniae Mass azithromycin did not significantly alter the pneumococcal serotype distribution, and hence it would not be expected to alter vaccine coverage.

Topics: Anti-Bacterial Agents; Azithromycin; Carrier State; Child; Child, Preschool; Cross-Sectional Studies; Ethiopia; Humans; Infant; Pneumococcal Infections; Serogroup; Streptococcus pneumoniae; Trachoma

To explore the efficacy of the ketolide telithromycin compared with azithromycin in eradicating S pneumoniae from the nasopharynx of adults with acute maxillary sinusitis. The growing resistance of Streptococcus pneumoniae to penicillin and macrolides brought about the development of a new class of antibiotics-the ketolides-that are effective against resistant pneumococci.. Otolaryngology clinic.. One-hundred five patients with acute maxillary sinusitis.. Nasopharyngeal cultures were obtained before therapy and 10 to 12 days after initiation of treatment. Fifty-nine patients were treated with 500 mg of azithromycin daily for 3 days and 46 were treated with 800 mg of telithromycin daily for 5 days.. Sixty-seven potential pathogens were recovered prior to initiation of therapy in 57 patients, 32 treated with telithromycin and 25 treated with azithromycin: S pneumoniae (31 isolates), Haemophilus influenzae (non-type b) (13), Staphylococcus aureus (8), Streptococcus pyogenes (8), and Moraxella catarrhalis (7). The distribution of the pathogens was similar in both groups. The number of S pneumoniae isolates in the azithromycin group was reduced following treatment from 14 to 8 (43% reduction), and 5 of these 8 isolates were resistant to azithromycin. In contrast, the number of S pneumoniae isolates in the telithromycin group was reduced following treatment from 17 to 1 (94% reduction) (P < .01). This isolate was susceptible to azithromycin and telithromycin. No differences were noted in the eradication rate of all of the other potential pathogens, which were all susceptible to both azithromycin and telithromycin. Development of resistance to the antimicrobial agents used (defined as increase in the minimal inhibitory concentration by at least 2 tubes) was found only in 5 isolates (4 S pneumoniae and 1 H influenzae) recovered only from patients who received azithromycin (P < .05).. These data illustrate the superiority of telithromycin to azithromycin in the eradication of S pneumoniae from the nasopharynx.

Topics: Acute Disease; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Female; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged; Pneumococcal Infections; Streptococcus pneumoniae

High dose amoxicillin is recommended for the initial treatment of children with acute otitis media (AOM), particularly patients at risk for having drug-resistant Streptococcus pneumoniae. Single dose azithromycin (30 mg/kg) is considered an alternative agent for the treatment of AOM.. To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM.. This was a double blind, double dummy, multinational, clinical trial in which children (6-30 months of age) with AOM were randomized to treatment with single dose azithromycin (30 mg/kg) or high dose amoxicillin (90 mg/kg/d, in 2 divided doses) for 10 days. Tympanocentesis was performed at baseline and clinical responses were assessed at days 12-14 (end of therapy) and at days 25-28 (end of study).. The study enrolled 313 patients, and 83% of the patients were < or =2 years of age. A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients. A middle ear pathogen was detected for 212 patients (68%). Haemophilus influenzae was the most common pathogen (isolated for 96 patients), followed by S. pneumoniae (92 patients), Moraxella catarrhalis (23 patients) and Streptococcus pyogenes (23 patients). beta-Lactamase production was observed for 17% of H. influenzae isolates and 100% of M. catarrhalis isolates. Thirty-five (38%) S. pneumoniae isolates were penicillin-nonsusceptible and 24 (26%) isolates were macrolide-resistant. At the end of therapy, clinical success rates for azithromycin and amoxicillin were comparable for all patients (84 and 84%, respectively) and for children < or =2 years of age (82 and 82%, respectively). At the end of therapy and end of study, clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin (80%) and patients treated with amoxicillin (83%). The rates of treatment-related adverse events for azithromycin and amoxicillin were 20% and 29%, respectively (P = 0.064). Diarrhea was more common in the amoxicillin group than in the azithromycin group (17.5 and 8.2%, respectively) (P = 0.017). Compliance, defined as completion of > or =80% of the study medication, was higher in the azithromycin group (100%) than in the amoxicillin group (90%) (P = 0.001).. In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Moraxellaceae Infections; Otitis Media; Patient Compliance; Pneumococcal Infections; Streptococcal Infections; Streptococcus pyogenes

Community-acquired pneumonia (CAP) is associated with considerable morbidity and mortality in both developed and developing countries. Despite research into the optimal management of this condition, there remains great variation in how patients with CAP are treated. A study was performed to assess the results of CAP treatment using a clinical pathway that incorporated admission guidelines, standard treatment orders with oral levofloxacin or cefuroxime axetil plus azithromycin, and an algorithm for oxygen therapy and discharge. The study involved seven centers enrolling 7,734 patients, 55% of whom were treated as outpatients and the remainder were admitted. Overall mortality was 8%, and increasing severity of illness, as assessed by pneumonia severity risk score, was associated with early mortality (within five days of admission) and late mortality (five or more days following admission). The use of the clinical pathway was associated with a reduction in early mortality. The use of levofloxacin alone or with cefuroxime axetil plus azithromycin was associated with decreased mortality compared with the use of other antibiotics.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Anti-Infective Agents; Azithromycin; Cefuroxime; Community-Acquired Infections; Critical Pathways; Drug Therapy, Combination; Female; Humans; Levofloxacin; Longitudinal Studies; Male; Middle Aged; Ofloxacin; Oxygen Inhalation Therapy; Pneumococcal Infections; Pneumonia; Pneumonia, Bacterial; Treatment Outcome

The efficacy and safety of azithromycin prophylaxis of community-acquired pneumonia (CAP) in young adults in a military training centre of the Ministry of Defence of the Russian Federation located in the Central European Region of Russia were studied. Two prophylactic regimens with azithromycin vs. the control were evaluated: azithromycin, 500 mg/w for 8 weeks (R1), azithromycin, 1500 mg once upon the enrolment (R2) and no drugs (R3). Nasopharyngeal carriage of Streptococcuspneumoniae and its susceptibility to antibacterials were estimated thrice: before the exposure, after the exposure within the 9th week and after the exposure within the 20th week. The MLS(B) phenotype was suspected when the isolates were resistant to erythromycin and clindamycin. During the observation period of 22 weeks CAP was diagnosed in 20.2% of 678 subjects in group R3, 8.6% of 508 subjects in group R1 (Risk Ratio =0.4, 95% Cl = 0.3-0.6) and 10.3% of 507 subjects in group R2 (Risk Ratio = 0.5, 95% Cl = 0.4-0.7). The S.pneumoniae carriage rate at visit 0 was 34-35%, within the 9th week it was 75, 66 and 50% (p<0.05) in groups R1, R2 and R3 respectively, and within the 20th week it was 69, 57 and 36% in the same groups (p<0.05). At visit 0 no macrolide resistance was detected in any of the 40 isolates tested. The background level of intermediate penicillin resistance was revealed in 0-14% of the isolates. Dramatic growth of macrolide resistance was observed within the 9th week in group R1 (95.7%, 44 resistant strains, Azithro+Clinda resistance in 37% of them) and in group R2 (89.5%, 34 resistant strains, Azithro+Clinda resistance in 11.9% of them). By the 20th week the resistance rate decreased up to 40 % (16 resistant strains, Azithro+Clinda resistance in 10% of them) in group R1 and up to 22.6% (7 resistant strains, Azithro+Clinda resistance in 5.4% of them) in group R2. As for penicillin resistance, no unfavourable shifts were detected. The study demonstrated the effectiveness of the azithromycin prophylaxis of CAP in healthy young men at high transient risk of the disease, as well as the possible risk for selection of resistant endemic pathogens.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Carrier State; Clindamycin; Community-Acquired Infections; Drug Resistance, Bacterial; Erythromycin; Humans; Microbial Sensitivity Tests; Military Personnel; Nasopharyngeal Diseases; Penicillins; Pneumococcal Infections; Respiratory Tract Infections; Russia; Streptococcus pneumoniae

Antibiotic-resistant pneumococci are difficult to eradicate from middle ear fluid (MEF) and the nasopharynx (NP). Bacteriologic eradication from the NP and MEF during acute otitis media (AOM) by 3 common antibiotic drugs was prospectively evaluated. In 19 (16%) of 119 MEF culture-positive patients, an organism susceptible to the treatment drug (Haemophilus influenzae, Streptococcus pneumoniae, or both) was isolated from the initial MEF, whereas resistant S. pneumoniae was present in the NP; in 9 (47%) patients, the initial resistant NP organism (identified by serotyping, resistance to the administered drug, and pulsed-field gel electrophoresis) replaced the susceptible MEF organism within only a few days after initiation of treatment. In regions where resistant pneumococci are prevalent, antibiotics may not only fail to eradicate the organisms, but they may often induce MEF superinfection with resistant pneumococci initially carried in the NP. This is an important mechanism by which, in recently treated patients, AOM infections often become refractory to treatment.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Drug Resistance, Microbial; Drug Therapy, Combination; Ear, Middle; Female; Humans; Male; Nasopharynx; Otitis Media; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; Superinfection; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Invasive group A streptococcal (GAS) infections are a cause of serious morbidity and high mortality. There is a need for a simple, effective antimicrobial regimen that could be used to prevent invasive GAS disease in high risk situations. To assess azithromycin as a chemoprophylactic agent, we evaluated its efficacy for eradication of oropharyngeal (OP) GAS and its impact on the nasopharyngeal (NP) colonization rate of macrolide-resistant Streptococcus pneumoniae.. We obtained OP and NP swabs for GAS and pneumococcus culture, respectively, from 300 schoolmates of a child with an invasive GAS infection. GAS culture-positive students were treated with daily azithromycin (12 mg/kg/day) for 5 days. We obtained follow-up OP and NP swabs at 9 (Day 17) and 24 (Day 32) days post-treatment from those students identified as GAS carriers on Day 0 and determined macrolide susceptibility of GAS and pneumococcal isolates.. Of the 300 students swabbed 152 (50%) carried GAS in their oropharynx. On Day 17, efficacy of azithromycin for GAS eradication was 95% (140 of 147) for all students. NP colonization rates for pneumococci decreased from 46% (67 of 146) to 12% (17 of 144; P < 0.001) by Day 17 and to 20% (27 of 137; P < 0.001) by Day 32. The prevalence of erythromycin-resistant pneumococcal isolates increased from 2% (3 of 146) to 4% (6 of 144) by Day 17 and to 8% (11 of 137; P = 0.04) by Day 32.. Azithromycin is an effective short course regimen for eradication of oropharyngeal GAS. However, azithromycin selected for macrolide-resistant strains of pneumococci. These findings highlight the importance of determining the appropriate circumstances for antimicrobial prophylaxis to prevent invasive GAS infections.

Topics: Anti-Bacterial Agents; Azithromycin; Carrier State; Chi-Square Distribution; Child; Colony Count, Microbial; Confidence Intervals; Drug Administration Schedule; Drug Resistance, Microbial; Female; Humans; Male; Nasopharynx; Oropharynx; Pneumococcal Infections; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes; Treatment Outcome

The effect of antibiotic therapy on nasopharyngeal colonization by Streptococcus pneumoniae and Haemophilus influenzae was evaluated in children diagnosed with acute otitis media. Children were randomly assigned to receive either amoxicillin/clavulanate or azithromycin therapy, and nasopharyngeal swabs were obtained for culture before and after starting therapy. Amoxicillin/clavulanate therapy eradicated or suppressed all strains of S. pneumoniae susceptible to penicillin, 75% of strains with intermediate resistance, and 40% of strains resistant to penicillin. Azithromycin therapy cleared two-thirds of azithromycin-susceptible strains of S. pneumoniae but none of azithromycin-nonsusceptible strains. Selection for antibiotic-resistant strains in individual children was not observed in children who received amoxicillin/clavulanate therapy but was observed in 2 children who received azithromycin therapy. Carriage of H. influenzae was also reduced by antimicrobial therapy but more so by amoxicillin/clavulanate. Antibiotic therapy does not directly increase the number of resistant strains in the population but, by eradicating susceptible strains, allows greater opportunity for carriage and spread of resistant strains.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Carrier State; Child; Child, Preschool; Clavulanic Acid; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Nasopharynx; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

A prospective assessment of the pharyngeal colonization prevalence rates for Streptococcus pyogenes and Streptococcus pneumoniae before and after an azithromycin chemoprophylaxis intervention clinical trial in a cohort of US Marine Corps trainees. In addition, the minimum inhibitory concentrations (MICs) for all streptococcal isolates, for azithromycin, penicillin, erythromycin and cefotaxime are reported.. Between November 1994 and March 1995, 1108 asymptomatic male US Marine Corps trainees, located in Southern California, were randomly assigned to one of three intervention groups: (1) weekly oral azithromycin, 500 mg (n = 362); (2) 1.2 MU benzathine penicillin G, intramuscularly once (n = 374); or (3) no chemoprophylaxis (n = 372). Subjects provided both a pre- and post-training pharyngeal culture and microbial analysis was conducted to determine the colonization status of each study subject.. The pretraining colonization prevalence was 1.2% for S. pneumoniae and 2.4% for S. pyogenes. There was no statistical difference in pretraining prevalence between the three treatment groups for either organism. Post-training pharyngeal cultures revealed an overall prevalence of 1.1% with no difference between treatment arms. However, the overall post-training prevalence of S. pyogenes colonization increased to 4.8%, with the azithromycin group having significant evidence of protection (0.7%) in comparison with the no-treatment group (8.2%). The Etest method demonstrated no significant difference in the MIC50, MIC90, and MIC ranges between pre- and post-training isolates for any of the tested drugs.. The use of azithromycin as a chemoprophylactic agent to reduce the colonization and subsequent infection of streptococcal respiratory disease among healthy adult male military recruits may be beneficial.

Topics: Anti-Bacterial Agents; Azithromycin; Cohort Studies; Humans; Male; Microbial Sensitivity Tests; Penicillins; Pharynx; Pneumococcal Infections; Prevalence; Prospective Studies; Respiratory Tract Infections; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

In February 1995, single-dose azithromycin was given to children with trachoma and their household contacts who were children. For children with trachoma, rates of carriage of pneumococci immediately before treatment with azithromycin and 2-3 weeks, 2 months, and 6 months after treatment were 68% (54 of 79), 29% (11 of 38), 78% (29 of 37), and 87% (34 of 39), respectively. The proportion of carriage-positive children with azithromycin-resistant Streptococcus pneumoniae strains was 1 of 54 (1.9%) before treatment and then 6 of 11 (54.5%), 10 of 29 (34.5%), and 2 of 34 (5.9%) at follow-up visits. The profile of pneumococcal serotypes changed after azithromycin treatment. Azithromycin-resistant strains (serotypes 10F, 23A, and 45) were isolated from 1 (1.3%) of 79 pretreatment swab specimens, from 16 (21.3%) of 75 swab specimens collected up to 2 months after treatment, and from 2 (6%) of 32 obtained 6 months after treatment. Mathematical modeling showed a more rapid appearance of azithromycin-resistant pneumococcal strains in previously colonized children than in previously noncolonized children. Thus, it appears that the selective effect of azithromycin allowed the growth and transmission of preexisting azithromycin-resistant strains. More research is needed to clarify the clinical relevance and implications of azithromycin use.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Carrier State; Child; Child, Preschool; Drug Resistance, Microbial; Erythromycin; Humans; Longitudinal Studies; Nasopharynx; Native Hawaiian or Other Pacific Islander; Northern Territory; Pneumococcal Infections; Prospective Studies; Streptococcus pneumoniae; Trachoma

In this multicenter, open label trial the investigators evaluated the efficacy and safety of azithromycin suspension administered once daily for 5 days for the treatment of clinically and bacteriologically established acute otitis media.. Two hundred eligible children with acute otitis media from 10 US centers were treated with 10 mg/kg of azithromycin oral suspension on Day 1, followed by 5 mg/kg once daily for the next 4 days. Tympanocentesis and subsequent culture of middle ear effusion were performed at baseline. Clinical efficacy was evaluated on Days 6, 11 and 30.. Analysis of clinical efficacy in evaluable patients 11 days after the initiation of therapy showed that the rate of satisfactory responses (cured or improved) ranged from 79.6 to 82.4% in patients infected with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. Satisfactory clinical response at Day 30 was reported in 70% of evaluable patients, and eradication of S. pneumoniae, H. influenzae and M. catarrhalis was presumed in 64 to 73%. Relapses occurred in 14% of the evaluable patients. Among the treated patients 8.5% reported mild or moderate side effects.. Azithromycin is an effective, safe and well-tolerated treatment for children with acute otitis media.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Administration Schedule; Female; Haemophilus Infections; Humans; Male; Moraxella catarrhalis; Neisseriaceae Infections; Otitis Media; Pneumococcal Infections

Topics: Azithromycin; Carrier State; Child, Preschool; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Pharynx; Pneumococcal Infections; Streptococcus pneumoniae; Tetracycline; Trachoma

The efficacy and safety of a three-day regimen of azithromycin (500 mg od) and a ten-day regimen of co-amoxiclav (625 mg tid) were compared in a single-blind study in 99 patients with acute lower respiratory tract infections. Of these, 70 (71%) suffered an infective exacerbation of their chronic obstructive pulmonary disease. Nine patients had pneumonia and 19 purulent bronchitis. Treatment success, defined as cure or improvement, occurred in 43 of 48 (90%) patients in the azithromycin group, compared with 45 of 51 (88%) patients in the co-amoxiclav group. The most common isolated pathogens were Haemophilus influenzae (25 cases; MIC range of azithromycin (A) < or = 0.06-4 mg/L; for co-amoxiclav (CA) 0.25-4 mg/L; Streptococcus pneumoniae (10 cases; A: < or = 0.06- > 128; CA: < or = 0.06); and Moraxella catarrhalis (four cases; A: < or = 0.06; CA: < or = 0.06-0.25). Microbiological response rates were comparable in the two groups. In 5% of patients, serological evidence for virus or atypical pathogens was found. Thirteen (26%) patients treated with co-amoxiclav had gastrointestinal complaints (seven with diarrhoea), compared with five (10%) treated with azithromycin (P = 0.09). Additional complaints occurred in three patients treated with co-amoxiclav and in one patient treated with azithromycin. It was concluded that a three-day regimen of azithromycin was as effective, clinically and microbiologically, as a ten-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections.

Topics: Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Bronchitis; Clavulanic Acids; Drug Administration Schedule; Drug Combinations; Erythromycin; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Single-Blind Method; Streptococcus pneumoniae

Topics: Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Alanine; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Azithromycin; Ceftriaxone; Coinfection; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Dexamethasone; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Pneumococcal Infections; SARS-CoV-2; Streptococcus pneumoniae

Topics: Azithromycin; Bacterial Typing Techniques; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; High-Throughput Nucleotide Sequencing; Hospitals, Pediatric; Humans; Infant; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Myanmar; Phylogeny; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae; Tetracycline; Whole Genome Sequencing

Mass drug administration (MDA) with azithromycin (AZ) has been used successfully to control trachoma. However, several studies have shown that MDA with AZ has led to the emergence of resistance to AZ in

Topics: Amodiaquine; Anti-Bacterial Agents; Antimalarials; Azithromycin; Burkina Faso; Carrier State; Chemoprevention; Child, Preschool; Drug Combinations; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Infant; Malaria; Male; Mass Drug Administration; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Pyrimethamine; Seasons; Serogroup; Streptococcus pneumoniae; Sulfadoxine

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Drug Resistance, Bacterial; Humans; Infant; Macrolides; Niger; Pneumococcal Infections; Streptococcus pneumoniae

Current knowledge of the emergence of

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Models, Biological; Pneumococcal Infections; Streptococcus pneumoniae

To determine antibiotic susceptibility of isolates of Streptococcus pneumoniae (n = 573) and Haemophilus influenzae (n = 345) collected in 2014-16 from Bulgaria, Romania, Serbia and Croatia.. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.. Among S. pneumoniae, susceptibility was generally lowest in Romania and Serbia and highest in Bulgaria. Rates of susceptibility to penicillin (CLSI oral or EUCAST) were 22.3% and 21.8% in Romania and Serbia respectively, 57% in Croatia and 86.6% in Bulgaria. Similarly, macrolide susceptibility using CLSI/EUCAST breakpoints was low in Romania and Serbia (∼28% and 34.5%, respectively), higher in Croatia (55.9%) and highest in Bulgaria (∼75%). Only fluoroquinolones were active against all isolates in all four countries. Susceptibility was higher and variability across countries less pronounced for H. influenzae. Susceptibility by CLSI criteria to amoxicillin/clavulanic acid, azithromycin, cefuroxime, ceftriaxone and fluoroquinolones was ≥98% in all countries. Ampicillin susceptibility ranged from 85.3% in Romania to 100% in Bulgaria. Much greater variability was seen across breakpoints. Susceptibility to azithromycin and cefuroxime using CLSI criteria was ≥98% in all four countries, but was 0%-1% by EUCAST criteria.. The variability in antimicrobial susceptibility using different breakpoints makes it difficult for clinicians to interpret antimicrobial resistance data, and efforts should be made to harmonize breakpoints. The variability found across the four neighbouring countries demonstrates the need to monitor and publish national and local resistance patterns. These findings provide information critical for the selection of appropriate antimicrobial agents for the treatment of S. pneumoniae and H. influenzae.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bulgaria; Child; Community-Acquired Infections; Croatia; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Haemophilus Infections; Haemophilus influenzae; Humans; Macrolides; Microbial Sensitivity Tests; Middle Aged; Pneumococcal Infections; Respiratory Tract Infections; Romania; Serbia; Streptococcus pneumoniae; Surveys and Questionnaires; Young Adult

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Macrolides; Microbial Sensitivity Tests; N-Acetylmuramoyl-L-alanine Amidase; Pneumococcal Infections; Streptococcus pneumoniae; Streptolysins

The bacteria Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) are leading causes of childhood pneumonia and meningitis and are major contributors to worldwide mortality in children younger than 5 years of age. Asymptomatic nasopharyngeal carriage of pneumococcus and Hib was determined for healthy children in Shanghai in 2009.. Children from 5 immunization clinics were enrolled in this study. Specimens from the nasopharynx were collected and cultured in Columbia and chocolate agar to identify pneumococcal and Hib carriage. Pneumococcal specimens were serotyped with the Neufeld test, and antibiotic resistance for pneumococcal and Hib specimens used the E-test method. Significance of risk factors for carriage was assessed through chi-square tests.. Among 614 children, 16.6% had pneumococcal carriage and 8.0% Hib carriage. The predominant serotype of pneumococcus that was isolated was 19 F (52.9%); serotype coverage was 68.6% for both 7-valent pneumococcal conjugate vaccine (PCV) and PCV-10, and 82.3% for PCV-13. Household residency and father's education were both significantly related to pneumococcal and Hib carriage. The majority of S. pneumoniae isolates were sensitive to most antimicrobials but there were high levels of resistance to azithromycin (51.0 %) and erythromycin (51.0%). Haemophilus influenzae isolates were sensitive to almost all antimicrobials tested although 12.2% of isolates were resistant to ampicillin.. The pneumococcal and Hib vaccines require payment, and the children with the highest burden of disease may not be receiving these vaccines. Moreover, the presence of high antibiotic susceptibility towards pneumococcus, and to a lesser extent towards Hib, underscores the need for preventive protection against these diseases. Public funding of pneumococcal and Hib vaccines would be one mechanism to increase uptake of these vaccines.

Topics: Anti-Infective Agents; Azithromycin; China; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae type b; Humans; Infant; Male; Microbial Sensitivity Tests; Nasopharynx; Odds Ratio; Pneumococcal Infections; Streptococcus pneumoniae

A clinical trial of mass azithromycin distributions for trachoma created a convenient experiment to test the hypothesis that antibiotic use selects for clonal expansion of preexisting resistant bacterial strains.. Twelve communities in Ethiopia received mass azithromycin distributions every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored by means of nasopharyngeal swab sampling before mass azithromycin distribution and after 4 mass treatments. Swab specimens were tested for Streptococcus pneumoniae, and isolates underwent multilocus sequence typing.. Of 82 pneumococcal isolates identified before treatment, 4 (5%) exhibited azithromycin resistance, representing 3 different sequence types (STs): 177, 6449, and 6494. The proportion of isolates that were classified as one of these 3 STs and were resistant to azithromycin increased after 4 mass azithromycin treatments (14 of 96 isolates [15%]; P = .04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P < .0001). The diversity of STs-as calculated by the unbiased Simpson index-decreased significantly after mass azithromycin treatment (P = .045).. Resistant clones present before mass azithromycin treatments increased in frequency after treatment, consistent with the theory that antibiotic selection pressure results in clonal expansion of existing resistant strains.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Genes, Bacterial; Humans; Infant; Infant, Newborn; Male; Multilocus Sequence Typing; Nasal Cavity; Pneumococcal Infections; Streptococcus pneumoniae

This study investigated the molecular characteristics of azithromycin-resistant Streptococcus pneumoniae in Taiwan.. A total of 486 non-duplicate isolates of azithromycin-resistant S. pneumoniae recovered from various clinical sources of patients treated at 22 different hospitals in Taiwan from 2006 to 2010. The presence of erm(B) and mef(A) genes using duplex PCR, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis of these isolates were studied.. Of the isolates tested, 59% carried the erm(B) gene, 22% carried the mef(A) gene, and 19% carried both genes. The prevalence of isolates carrying the erm(B) and mef(A) genes increased from 10% (11/110) in 2006 to 25% (15/60) in 2010 (p-value = 0.0136). The majority of isolates carrying both erm(B) and mef(A) genes belonged to serotypes 19 F (64%) followed by 19 F A (24%). Of these isolates, 33% were sequence type 320 (ST320), 32% were ST236, and 12% were ST271.. The increase in incidence of mef(A)/erm(B)-positive azithromycin-resistant S. pneumoniae isolates during the study period was primarily due to serotypes 19 F and 19A and ST236 and ST320.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Male; Membrane Proteins; Methyltransferases; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Pneumococcal Infections; Polymerase Chain Reaction; Streptococcus pneumoniae; Taiwan

Topics: Anti-Bacterial Agents; Azithromycin; Carrier State; Female; Humans; Male; Pneumococcal Infections; Trachoma

Emerging evidence suggests that the mass distribution of azithromycin for trachoma control (MDA) may increase circulation of macrolide resistance in bacteria associated with severe pediatric infections in treated communities.. We examined the effect of MDA on nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae among 1015 young children living in rural Tanzania. MDA with a single dose of oral azithromycin was provided in 4 of 8 communities where trachoma prevalence was ≥10%. Isolates were tested for susceptibility to azithromycin (AZM) and commonly used antibiotics by disk diffusion and Etest. We calculated the proportion of antibiotic-resistant S. pneumoniae carriage at baseline and again 1, 3, and 6 months after treatment, and at comparable intervals in the untreated villages.. The proportion of AZM-resistant isolates was similar between groups at baseline (MDA: 35.8% vs non-MDA: 35.4%), however, this proportion was greater in the MDA group in all subsequent surveys. At 6 months, the percentage of AZM-resistant isolates was significantly higher in the MDA group (81.9% vs 46.9%, P < .001). The odds of AZM-resistant carriage was 5-fold greater in the MDA group (odds ratio, 4.95 [95% confidence interval, 3.23-7.61]). The proportion of isolates clinically resistant to AZM (minimum inhibitory concentration ≥16 µg/mL) was also significantly greater in the MDA group at 6 months (35.3% vs 12.4%, P < .006).. Mass distribution of a single dose of oral azithromycin for trachoma was associated with increased circulation of macrolide-resistant S. pneumoniae carriage among young children in the 6 months following treatment. It is crucial that changes in antibiotic resistance patterns and their clinical significance in the treatment of severe pediatric infections be assessed in future MDA trials.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Carrier State; Child, Preschool; Cohort Studies; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Pneumococcal Infections; Prevalence; Risk Factors; Streptococcus pneumoniae; Tanzania; Trachoma

Previous work showed a higher prevalence of macrolide/azalide resistance in provinces of Canada where azithromycin was the major treatment for Streptococcus pneumoniae as compared with regions where clarithromycin was the dominant treatment. These data provided a way to test the mutant selection window hypothesis, which predicts that the serum drug concentration (AUC(24)) relative to the mutant prevention concentration (MPC) would be higher for clarithromycin than for azithromycin.. The MIC and MPC were determined for 191 penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with azithromycin, clarithromycin and erythromycin using agar plate assays.. The MIC(50/90) (mg/L) and MPC(50/90) (mg/L), respectively, were as follows: azithromycin 0.13/0.25 and 1/4; clarithromycin 0.031/0.063 and 0.13/0.5; erythromycin 0.063/0.13 and 0.25/2. We calculated from published pharmacokinetic values that the AUC(24)/MPC(90) for azithromycin was 0.85; for clarithromycin it was 96, and for erythromycin base and estolate it was 4 and 10, respectively. Thus the AUC(24)/MPC(90) was about 50 times higher for clarithromycin than for azithromycin.. The elevated prevalence of azithromycin resistance may derive in part from a low value of AUC(24)/MPC(90) and/or time above MPC, since previous work indicates that the number of prescriptions per person was similar in the geographical regions examined.

Topics: Anti-Bacterial Agents; Attention; Azithromycin; Canada; Clarithromycin; Erythromycin; Humans; Microbial Sensitivity Tests; Mutation; Pneumococcal Infections; Streptococcus pneumoniae

Laboratory studies have suggested that antibiotic resistance may result in decreased fitness in the bacteria that harbor it. Observational studies have supported this, but due to ethical and practical considerations, it is rare to have experimental control over antibiotic prescription rates.. We analyze data from a 54-month longitudinal trial that monitored pneumococcal drug resistance during and after biannual mass distribution of azithromycin for the elimination of the blinding eye disease, trachoma. Prescription of azithromycin and antibiotics that can create cross-resistance to it is rare in this part of the world. As a result, we were able to follow trends in resistance with minimal influence from unmeasured antibiotic use. Using these data, we fit a probabilistic disease transmission model that included two resistant strains, corresponding to the two dominant modes of resistance to macrolide antibiotics. We estimated the relative fitness of these two strains to be 0.86 (95% CI 0.80 to 0.90), and 0.88 (95% CI 0.82 to 0.93), relative to antibiotic-sensitive strains. We then used these estimates to predict that, within 5 years of the last antibiotic treatment, there would be a 95% chance of elimination of macrolide resistance by intra-species competition alone.. Although it is quite possible that the fitness cost of macrolide resistance is sufficient to ensure its eventual elimination in the absence of antibiotic selection, this process takes time, and prevention is likely the best policy in the fight against resistance.

Topics: Algorithms; Analysis of Variance; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Drug Resistance, Bacterial; Ethiopia; Genetic Association Studies; Humans; Membrane Proteins; Microbial Viability; Models, Genetic; Pneumococcal Infections; Prevalence; Streptococcus pneumoniae; Trachoma

A study published in 1998 linking MMR vaccine and autism was recently retracted by the Lancet because the data were falsified. The impressive reduction of invasive pneumococcal diseases with the 7-valent pneumococcal conjugate vaccine is due to a more than 90% reduction in rates of infections due to vaccinal serotypes at the expense of a slight increase in non-vaccinal serotypes. Genes encoding resistance factors to several antibiotic classes were detected in 30000-year-old samples. New Delhi metallo-beta-lactamase 1 was frequently detected in street water in New Dehli. Azithromycin decreased COPD exacerbations in a select group of patients with COPD at the cost of more frequent small decrements in hearing. Cranberry juice did not prevent recurrent urinary tract infections. Some patients with persistent symptoms after Lyme disease had higher levels of anti-Borrelia antibodies than cured patients.

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactamase Inhibitors; beta-Lactamases; Communicable Disease Control; Communicable Diseases; Drug Resistance, Microbial; Epidemiology; Humans; Lyme Disease; Measles; Measles-Mumps-Rubella Vaccine; Pneumococcal Infections; Pneumococcal Vaccines; Pulmonary Disease, Chronic Obstructive; Serotyping; Vaccines, Conjugate

A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N'-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N'-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N'-(β-cyanoethyl)-N'-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N'-(β-cyanoethyl)-N'-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3). Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Models, Molecular; Pneumococcal Infections; Streptococcus pneumoniae; Thiourea; Urea

Synthesis, antibacterial activity and pharmacokinetic properties of a novel class of macrolide antibiotics-macrolones-derived from azithromycin, comprising oxygen atom(s) in the linker and either free or esterified quinolone 3-carboxylic group, are reported. Selected compounds showed excellent antibacterial potency towards key erythromycin resistant respiratory pathogens. However, the majority of compounds lacked good bioavailability. The isopropyl ester, compound 35, and a macrolone derivative with an elongated linker 29 showed the best oral bioavailability in rats, both accompanied with an excellent overall microbiology profile addressing inducible and constitutive MLSb as well as efflux mediated macrolide resistance in streptococci, while compound 29 is more potent against staphylococci.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Azithromycin; Biological Availability; Carboxylic Acids; Crystallography, X-Ray; Drug Stability; Esters; Humans; Injections, Intravenous; Macrolides; Male; Microbial Sensitivity Tests; Microsomes, Liver; Models, Molecular; Pneumococcal Infections; Rats; Rats, Wistar; Streptococcus pneumoniae

Three novel structural series of C-4'' modified azithromycin analogs with two amide groups, which were connected by different alkyl linkage, were designed, prepared and evaluated for their in vitro antibacterial activity against seven phenotypes of respiratory pathogens. Among them, 7d, 8j and 9j, as representatives of corresponding series, exhibited remarkably improved activity against erythromycin-resistant Streptococcus pneumoniae expressing the erm gene, the mef gene, and the erm and mef genes. In addition, 7a-c, 7f-h, 7j, 8d, 8g, 8i, 9a-b and 9i displayed favorable efficacy against erythromycin-resistant S. pneumoniae A22072 expressing the mef gene.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Drug Resistance, Bacterial; Erythromycin; Gene Expression; Humans; Membrane Proteins; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae

In the present study, the serotype distribution and antibiotic resistance of S. pneumoniae from pediatric patients with upper respiratory infections in Beijing, 2010 were described. 140 pneumococcal isolates were obtained, and the prevailing five serotypes were 19F (18.6%), 23F (9.3%), 14 (9.3%), 15 (9.3%), and 6A (7.1%). The vaccine coverage of PCV7, PCV10, and PCV13 were 43.6%, 43.6%, and 60.0%, respectively. According to the CLSI 2010 criteria, 99.3% of the S. pneumoniae isolates were susceptible to penicillin. The resistance rates to erythromycin and azithromycin were 96.4% and 97.1%, respectively. Meanwhile, 64.3% (90/140) of all pneumococcal isolates were multidrug-resistant S. pneumoniae (MDRSP). PCV13 covered 68.9% (62/90) of MDRSP strains, whereas it was 47.8% (43/90) for PCV7. ErmB was the dominant macrolide-resistance gene, whereas 30.4% pneumococcal isolates expressed both ermB and mefA. No isolate expressed ermTR. The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 6A and 19A, and the conjugate vaccines could prevent the spread of MDRSP. S. pneumoniae is still sensitive to penicillin. The resistance rate of S. pneumoniae to macrolides is high and ermB is the dominant macrolide-resistance gene in China, so continued surveillance of the antimicrobial susceptibility of S. pneumoniae may be necessary.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; China; Drug Resistance, Bacterial; Erythromycin; Genes, Bacterial; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Respiratory Tract Infections; Serotyping; Streptococcus pneumoniae

Macrolide resistance in Streptococcus pneumoniae has emerged as an important clinical problem worldwide over the past decade. The aim of this study was to analyze the phenotypes (serotype and antibiotic susceptibility), genotypes (multilocus sequence type [MLST] and antibiotic resistance gene/transposon profiles) among the 31% (102/328) of invasive isolates from children in New South Wales, Australia, in 2005 that were resistant to erythromycin. Three serotypes--19F (47 isolates [46%]), 14 (27 isolates [26%]), and 6B (12 isolates [12%])--accounted for 86 (84%) of these 102 isolates. Seventy four (73%) isolates had the macrolide-lincosamide-streptogramin B (MLS(B)) resistance phenotype and carried Tn916 transposons (most commonly Tn6002); of these, 73 (99%) contained the erythromycin ribosomal methylase gene [erm(B)], 34 (47%) also carried the macrolide efflux gene [mef(E)], and 41 (55%) belonged to serotype 19F. Of 28 (27%) isolates with the M phenotype, 22 (79%) carried mef(A), including 16 (57%) belonging to serotype 14, and only six (19%) carried Tn916 transposons. Most (84%) isolates which contained mef also contained one of the msr(A) homologues, mel or msr(D); 38 of 40 (95%) isolates with mef(E) (on mega) carried mel, and of 28 (39%) isolates with mef(A), 10 (39%) carried mel and another 11(39%) carried msr(D), on Tn1207.1. Two predominant macrolide-resistant S. pneumoniae clonal clusters (CCs) were identified in this population. CC-271 contained 44% of isolates, most of which belonged to serotype 19F, had the MLS(B) phenotype, were multidrug resistant, and carried transposons of the Tn916 family; CC-15 contained 23% of isolates, most of which were serotype 14, had the M phenotype, and carried mef(A) on Tn1207.1. Erythromycin resistance among S. pneumoniae isolates in New South Wales is mainly due to the dissemination of multidrug-resistant S. pneumoniae strains or horizontal spread of the Tn916 family of transposons.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Child, Preschool; DNA Transposable Elements; Drug Resistance, Bacterial; Erythromycin; Genotype; Humans; Macrolides; Microbial Sensitivity Tests; New South Wales; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae

Topics: Africa; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Bacterial; Humans; Immunity, Herd; Infant; Pneumococcal Infections; Streptococcus pneumoniae; Trachoma

Of 393 isolates of Streptococcus pneumoniae from U.S. children collected in 2005-2006, nonvaccine serotypes accounted for 89.1%, with serotype 19A the most prevalent, representing 30.5% of all isolates. The MIC(90) of faropenem against serotype 19A isolates was 1 mug/ml, compared to > or =8 microg/ml against amoxicillin/clavulanate, cefdinir, cefuroxime axetil, and azithromycin.

Topics: Adolescent; Anti-Bacterial Agents; beta-Lactams; Child; Child, Preschool; Drug Resistance, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Phenotype; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; United States

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Humans; Indians, North American; Infections; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae

Antimicrobial resistance of pneumococci is influenced by serotypes, antimicrobial consumption and vaccine use. Serotyping of 697 out of 1331 pneumococcal isolates, recovered in Portugal from 1994 to 2004, showed that the theoretical rate of heptavalent conjugate vaccine coverage was 91.7% and 63.6% for penicillin and erythromycin non-susceptible strains, respectively, in children up to 1 year old. The use of amoxicillin and erythromycin decreased in the vaccine period 2001-2004 (P=0.04 and P<0.01, respectively) but azithromycin usage increased in the same period (P<0.01). By using linear regression models, we evaluated the role of antimicrobial and vaccine use in the trends of resistance to penicillin and erythromycin among the isolates. The models suggest that the use of macrolides was the main factor associated with an increase of penicillin and erythromycin non-susceptible isolates from adults (P<0.01) and erythromycin non-susceptible isolates among children (P=0.006). These models also suggest that heptavalent vaccine is failing to reduce antimicrobial resistance as expected, possibly due to the increased consumption of azithromycin (P=0.04). The efficient use of new antibiotics may reverse the present trends of antimicrobial resistance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Bacterial; Erythromycin; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Infant, Newborn; Macrolides; Meningococcal Vaccines; Middle Aged; Models, Statistical; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Portugal; Serotyping; Streptococcus pneumoniae

LBM415 is a peptide deformylase inhibitor active against gram-positive bacterial species and some gram-negative species. In multiselection studies, LBM415 had low MICs against all Streptococcus pneumoniae strains tested, regardless of their genotype, and selected resistant clones after 14 to 50 days. MIC increases correlated with changes mostly in the 70GXGXAAXQ77 motif in peptide deformylase. The postantibiotic effect of LBM415 ranged from 0.3 to 1.4 h.

Topics: Amidohydrolases; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Peptides; Pneumococcal Infections; Species Specificity; Streptococcus pneumoniae; Time Factors

A rare clinical isolate of Streptococcus pneumoniae, highly resistant to telithromycin, contained erm(B) with a truncated leader peptide and a mutant ribosomal protein L4. By transformation of susceptible strains, this study shows that high-level telithromycin resistance is conferred by erm(B), wild type or mutant, in combination with a (69)GTG(71)-to-TPS mutation in ribosomal protein L4.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Culture Media; Drug Resistance, Bacterial; Genotype; Humans; Ketolides; Methyltransferases; Microbial Sensitivity Tests; Mutation; Phenotype; Pneumococcal Infections; Ribosomal Proteins; Streptococcus pneumoniae

The aim of this study was to analyze the distributions of antibiotic susceptibility patterns, serotypes, phenotypes, genotypes, and macrolide resistance genes among 125 nonduplicated erythromycin-resistant Streptococcus pneumoniae clinical isolates collected in a Spanish point prevalence study. The prevalence of resistance to macrolides in this study was 34.7%. Multiresistance (to three or more antimicrobials) was observed in 81.6% of these strains. Among 15 antimicrobials studied, cefotaxime, moxifloxacin, telithromycin, and quinupristin-dalfopristin were the most active drugs. The most frequent serotypes of erythromycin-resistant isolates were 19F (25%), 19A (17%), 6B (12%), 14 (10%), and 23F (10%). Of the 125 strains, 109 (87.2%) showed the MLS(B) phenotype [103 had the erm(B) gene and 6 had both erm(B) and mef(E) genes]. Sixteen (12.8%) strains showed the M phenotype [14 with mef(E) and 2 with mef(A)]. All isolates were tested by PCR for the presence of the int, xis, tnpR, and tnpA genes associated with conjugative transposons (Tn916 family and Tn917). Positive detection of erm(B), tet(M), int, and xis genes related to the Tn916 family was found in 77.1% of MLS(B) phenotype strains. In 16 strains, only the tndX, erm(B), and tet(M) genes were detected, suggesting the presence of Tn1116, a transposon recently described for Streptococcus pyogenes. Five clones, namely, Sweden(15A)-25, clone(19F) ST87, Spain(23F)-1, Spain(6B)-2, and clone(19A) ST276, accounted for half of the MLS(B) strains. In conclusion, the majority of erythromycin-resistant pneumococci isolated in Spain had the MLS(B) phenotype, belonged to multiresistant international clones, and carried the erm(B), tet(M), xis, and int genes, suggesting the spread of transposons of the Tn916 family.

Topics: Anti-Bacterial Agents; Clone Cells; Drug Resistance, Multiple, Bacterial; Electrophoresis, Polyacrylamide Gel; Erythromycin; Genes, Bacterial; Microbial Sensitivity Tests; Phenotype; Pneumococcal Infections; Serotyping; Spain; Streptococcus pneumoniae; Tetracycline Resistance

The bacterial time-kill curves of azithromycin against four bacterial strains (Streptococcus pneumoniae/penicillin-intermediate, S. pneumoniae/penicillin-sensitive, Haemophilus influenzae and Moraxella catarrhalis) were determined by in vitro infection models. Eighteen different pharmacokinetic/pharmacodynamic models were fitted to the time-kill data using non-linear regression and compared for best fit. A simple, widely used E(max) model was not sufficient to describe the pharmacodynamic effects for the four bacterial strains. Appropriate models that gave good curve fits included additional terms for saturation of the number of bacteria (N(max)), delay in the initial bacterial growth phase and/or the onset of anti-infective activity (1-exp(-zt)) as well as a Hill factor (h) that captures the steepness of the concentration-response profile. Azithromycin was highly effective against S. pneumoniae strains and M. catarrhalis while the efficacy against H. influenzae was poor. Applications of these pharmacokinetic/pharmacodynamic models will eventually provide a tool for rational antibiotic dosing regimen decisions.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Models, Biological; Moraxella catarrhalis; Moraxellaceae Infections; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

There are few data on macrolide pharmacodynamics in pneumococcal infections. We evaluated pneumococcal area under the inhibitory concentration-time curve (AUIC) values at the point of hospital admission in 59 bacteraemic patients failing in the community and in 98 bacteraemic controls without macrolide exposure. The area under the 24-h concentration-time curve (AUC24) was calculated for each patient using age, weight and daily dose; using minimum inhibitory concentrations (MICs), the values of AUIC (i.e. AUC24/MIC) were then computed. Clinical and outcome information was also collected in hospital. Five of six patients who died of pneumococcal bacteraemia in hospital received azithromycin, with a mean AUIC of 8.1 prior to hospital admission. Resistant isolates were recovered in 35 (59%) macrolide failures and in only 28 (29%) controls (P=0.001). Azithromycin AUICs averaged 10 in failure patients and 17 in controls. For clarithromycin and erythromycin, the mean AUIC values in failures were 31 and 53, respectively, and the AUIC in controls was >100. Low AUIC values against Streptococcus pneumoniae precede macrolide failures in the community. Patient factors do not predict these outcomes and thus the most likely explanation for macrolide failure in the community is inadequate macrolide activity in patients who receive these antibiotics for treatment of organisms that are not sufficiently susceptible.

Topics: Anti-Bacterial Agents; Area Under Curve; Azithromycin; Bacteremia; Clarithromycin; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; Microbial Sensitivity Tests; Pneumococcal Infections; Retrospective Studies; Streptococcus pneumoniae; Treatment Failure

Authorities have suggested restriction of azithromycin use as a principal strategy to contain the spread of azithromycin-nonsusceptible Streptococcus pneumoniae (ANSP). In 83 children persistently colonized by pneumococcus during and after treatment of acute otitis media, 17 acquired a new strain, 9 of which were less susceptible to azithromycin than the original isolate. New appearance of ANSP was documented after both beta-lactam and azithromycin exposure. ANSP is likely to disseminate even with significant reduction of azithromycin use unless other antibiotic use is decreased as well.

Topics: Azithromycin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Otitis Media; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae

Asia has experienced a striking incidence of infection by highly resistant pneumococi containing both principal macrolide resistance determinants, namely, the mef efflux pump and the erm ribosomal methylase. mef/erm-containing pneumococci have not been identified in significant numbers in North America.. Pneumococci were isolated as part of a larger study in Cleveland, OH examining colonization patterns among children randomized to 1 of 4 outpatient antibiotics for acute otitis media. Azithromycin-resistant organisms were tested for the presence of mef and erm sequences by polymerase chain reaction. The clonal relationship of pneumococci containing both genes was determined by pulsed field gel electrophoresis and multilocus sequence testing. Selected characteristics of children harboring mef/erm-containing organisms were compared with other participants of the larger study.. Of 221 children colonized by pneumococci, 17 (7.7%) were colonized with an organism containing both determinants. All mef/erm-positive organisms demonstrated azithromycin minimum inhibitory concentrations > or =256 microg/mL and were coresistant to all other agents tested. The mef/erm-containing organisms were serotype 19A and 19F, all but 1 of which manifested similar pulsed field gel electrophoresis patterns. Multilocus sequence testing analysis indicated a relationship to the Taiwan-14 macrolide-resistant strain that has spread throughout Eastern Asia. More than one-third of children colonized by a mef/erm-containing organism had received > or =1 dose of conjugate pneumococcal vaccine, a significantly higher proportion than children carrying less resistant organisms (P< 0.01). No other characteristics distinguished children harboring a mef/erm-containing pneumococcus from other children enrolled in the larger study.. Clonally related mef/erm-containing serogroup 19 pneumococci were prominent among otherwise healthy children in a North American metropolitan area. Our findings suggest that spread of these organisms may be poorly contained by immunization.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Child; Child, Preschool; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Humans; Infant; Membrane Proteins; Methyltransferases; Microbial Sensitivity Tests; Molecular Epidemiology; Ohio; Otitis Media; Pneumococcal Infections; Polymerase Chain Reaction; Sequence Analysis, DNA; Serotyping; Streptococcus pneumoniae

Acute bacterial rhinosinusitis, which is a major health problem, is treated with antibiotics. We developed a mouse model of acute bacterial rhinosinusitis to gain a better understanding of the pathophysiology of the disease. Our goal was to investigate the response to acute rhinosinusitis when treated with either a bactericidal or a bacteriostatic antibiotic.. C57BL/6 mice were infected intranasally with Streptococcus pneumoniae. One day after inoculation, the mice were treated with either moxifloxacin (bactericidal) or azithromycin (bacteriostatic). Different groups were euthanized during the first five days post-inoculation. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were evaluated by flow cytometry.. Azithromycin led to rapid clearance of the bacteria and of the inflammation in contrast to placebo. Surprisingly, moxifloxacin showed a limited effect. Investigations of this limited effect of moxifloxacin suggested a high metabolic clearance, a low concentration at the site of infection, and low persistent post-antibiotic effects of moxifloxacin in mice.. Our animal model of acute sinusitis has great utility for studying the disease, but the difference between mice and man must always be considered in making extrapolations from animal experiments to the human experience.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Aza Compounds; Azithromycin; CD11b Antigen; CD4 Antigens; CD8 Antigens; Disease Models, Animal; Female; Fluoroquinolones; Male; Mice; Mice, Inbred C57BL; Moxifloxacin; Pneumococcal Infections; Quinolines; Rhinitis; Sinusitis; Streptococcus pneumoniae

The connection between regional rates of antimicrobial resistance in Streptococcus pneumoniae and regional antimicrobial use in Finland was investigated. During the 6-year study period of 1997 to 2002, a total of 31,609 S. pneumoniae isolates were tested for penicillin resistance and a total of 23,769 isolates were tested for macrolide resistance in 18 central hospital districts in Finland. The regional macrolide resistance rates were compared with the local use of (i) all macrolides pooled and (ii) azithromycin. The penicillin resistance levels were compared with the consumption data for (i) penicillins, (ii) cephalosporins, (iii) all beta-lactams pooled, and (iv) all macrolides pooled. A statistically significant association between macrolide resistance and total use of macrolides and the use of azithromycin was found. Moreover, total use of beta-lactams and total use of cephalosporins were significantly connected to low-level penicillin resistance. A statistically significant association between penicillin-nonsusceptible isolates and penicillin or total macrolide consumption was not found. In conclusion, total macrolide use and azithromycin use are associated with increased macrolide resistance, and beta-lactam use and cephalosporin use are connected to increased low-level penicillin resistance in S. pneumoniae. Unnecessary prescribing of macrolides and cephalosporins should be avoided.

Topics: Anti-Bacterial Agents; Azithromycin; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Finland; Hospitals; Humans; Macrolides; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

Isolates of Streptococcus pneumoniae collected over the first 4 years of the PROTEKT study were tested for susceptibility to penicillin, azithromycin and telithromycin. A total of 20,750 isolates were collected from 39 countries. Penicillin non-susceptibility rates were stable over the study period; overall, 21.8% of isolates were resistant. Azithromycin resistance increased from 31.0% in Year 1 to 36.3% in Year 4. Resistance rates for penicillin and azithromycin varied between countries and were highest in France, Spain, South Africa, USA and the Far East. Multidrug resistance in S. pneumoniae did not change significantly over the 4 years, with an overall rate of 38.6%. Telithromycin retained good activity against S. pneumoniae (0.1% of isolates resistant), including multidrug-resistant isolates.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Multiple, Bacterial; Global Health; Humans; Ketolides; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae

BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models.. MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays. Profiling of the pharmacokinetics and select tissue disposition in mice was determined and compared with that of the macrolide, azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were conducted using a peritonitis model, as well as lung and thigh burden models of infection.. BB-81384 selectively inhibited PDF with an IC(50) approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae pathogens. Pharmacokinetic analysis revealed good oral bioavailability and moderate clearance and volume of distribution. BB-81384 partitioning to lung tissue was similar in terms of magnitude and kinetics to that of the plasma compartment. Single-administration oral efficacy in a mouse peritonitis model was evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by approximately 5 and 3 log units in organ-burden models of lung and thigh infection, respectively.. BB-81384, a novel PDF inhibitor with good activity against S. pneumoniae in vitro, was the first compound of this class to be profiled for oral pharmacokinetics and tissue disposition and to demonstrate oral anti-pneumococcal efficacy in mice.

Topics: Amidohydrolases; Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Drug Therapy, Combination; Enzyme Inhibitors; Kinetics; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Muscle, Skeletal; Muscular Diseases; Neutropenia; Peritonitis; Piperazines; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Tissue Distribution

Topics: Aged; Anti-Infective Agents; Arthritis, Infectious; Arthroplasty, Replacement, Knee; Azithromycin; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Male; Ofloxacin; Pneumococcal Infections; Prosthesis-Related Infections; Rifampin; Vancomycin

Macrolide antibiotics, including azithromycin, have been implicated in the modulation of host immune responses, independently of their antimicrobial properties. The present work was designed to study the effect that azithromycin has on protective humoral immune responses induced by a 7-valent, polysaccharide, pneumococcal conjugate vaccine (PCV7). By use of a murine vaccination/challenge model, it was found that inoculation with azithromycin led to significantly lower primary antibody responses, decreased recall proliferative responses, and, in nasal cavities, impaired clearance of Streptococcus pneumoniae serotype 14 from the nasal cavities. The results demonstrate that azithromycin can be inhibitory with regard to protective immune responsiveness.

Topics: Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Colony Count, Microbial; Disease Models, Animal; Female; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Memory; Lymphocyte Activation; Meningococcal Vaccines; Mice; Mice, Inbred BALB C; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae

To study the phenotype and phylogenetic relatedness of invasive Streptococcus pneumoniae strains isolated in Portugal.. A total of 614 invasive S. pneumoniae strains, isolated in Portugal from 1999 to the first 6 months of 2002, were characterized using serotyping and antimicrobial susceptibility testing. National outpatient sale data for macrolides were compared with erythromycin resistance. We investigated the main clonal lineages from erythromycin-resistant strains of serotype 14 by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).. The emergence of erythromycin-resistant strains correlated well with the usage of azithromycin in Portugal during the period of the study (r=0.900, P=0.001). Serotype 14 made the largest contribution to this emergence. We found two clonal complexes (CC) among erythromycin-resistant strains: CC1 was formed by three sequence types (ST), ST156, ST143 and ST1042, and CC2 by ST15 and ST9. All STs described, except ST1042, are putative founders of clonal groups or subgroups from serotype 14 as defined in the pneumococcal MLST database.. This study suggests that macrolides usage is an important factor enhancing the spread of invasive erythromycin-resistant S. pneumoniae clones in Portugal. The study also makes a contribution to the understanding of spread of erythromycin-resistant clones in an international context.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Typing Techniques; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Erythromycin; Genotype; Microbial Sensitivity Tests; Phenotype; Phylogeny; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae

Among respiratory tract isolates of Streptococcus pneumoniae from children, resistance to penicillins, cephalosporins, macrolides, and trimethoprim-sulfamethoxazole (SXT) increases on an annual basis. Pediatric patients who do not respond to conventional therapy for respiratory tract infections someday may be treated with fluoroquinolones. In this study, MICs of beta-lactams, azithromycin, SXT, and levofloxacin were determined and interpreted by using NCCLS guidelines for isolates of S. pneumoniae (2,834 from children and 10,966 from adults), Haemophilus influenzae (629 from children and 2,281 from adults), and Moraxella catarrhalis (389 from children and 1,357 from adults) collected during the 2000-2001 and 2001-2002 respiratory illness seasons in the United States as part of the ongoing TRUST surveillance studies. Rates of resistance to penicillin, azithromycin, and SXT were > or = 7.5% higher among patients < or = 4 years old than among patients 5 to 10, 11 to 17, and > or = 18 years old in both the 2000-2001 and the 2001-2002 respiratory illness seasons. Levofloxacin resistance was detected in 2 of 2,834 isolates (0.07%) from patients <18 years old. Levofloxacin MICs of 0.25 to 1 micro g/ml accounted for 99.6, 99.5, 99.3, 99.7, 98.4, and 98.0% of isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old. Multidrug resistance was twice as common among patients < or = 4 years old (25.3%) as among patients 5 to 10 years old (13.7%), 11 to 17 years old (11.9%), 18 to 64 years old (12.1%), and > 64 years old (12.4%). The most common multidrug resistance phenotype in S. pneumoniae isolates for all age groups was resistance to penicillin, azithromycin, and SXT (70.3 to 76.6%). For H. influenzae and M. catarrhalis isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old, levofloxacin MICs at which 90% of the isolates were inhibited were 0.015 and 0.03 to 0.06 microg/ml, respectively, in the 2000-2001 and 2001-2002 respiratory illness seasons. In the 2000-2001 and 2001-2002 respiratory illness season surveillance studies in the United States, 99.9% of pediatric isolates of S. pneumoniae were susceptible to levofloxacin. If fluoroquinolones become a treatment option for pediatric patients, careful monitoring of fluoroquinolone susceptibilities will be increasingly important in future surveillance studies.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Lactams; Levofloxacin; Microbial Sensitivity Tests; Middle Aged; Moraxella catarrhalis; Ofloxacin; Pneumococcal Infections; Prospective Studies; Respiratory Tract Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Anti-Bacterial Agents; Azithromycin; Child; Drug Resistance, Multiple, Bacterial; Drug Utilization; Erythromycin; Humans; Microbial Sensitivity Tests; Otitis Media; Pneumococcal Infections; South Africa; Streptococcus pneumoniae; Treatment Outcome

We compared the activities of telithromycin, erythromycin, azithromycin, josamycin, penicillin G, amoxicillin, cefpodoxime, and ceftriaxone against invasive and noninvasive non-penicillin-susceptible Streptococcus pneumoniae isolates recovered from children. Of the 186 isolates tested, 89% were positive for erm(B) by PCR. Telithromycin had the lowest MICs, with MICs at which 90% of the isolates tested are inhibited of 0.032 and 0.25 micro g/ml for erythromycin-sensitive and -resistant isolates, respectively.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cefpodoxime; Ceftizoxime; Ceftriaxone; Child; Drug Resistance, Bacterial; Erythromycin; France; Humans; In Vitro Techniques; Josamycin; Ketolides; Macrolides; Penicillin G; Penicillin Resistance; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae

Penicillin binding protein (pbp) gene alterations of 328 clinical isolates of Streptococcus pneumoniae were examined for a correlation with their antibiotic-resistance. The frequency of penicillin G (PEN-G) resistance was determined to clarify susceptibility to several antibiotics, namely PEN-G, ampicillin, sulbactam/ampicillin, cefozopram, panipenem (PAPM), clarithromycin (CLR), azithromycin (AZM) and levofloxacin (LVX). Oligonucleotide primers for three pbp genes (pbp1a, pbp2x and pbp2b) were used to detect mutations in pbp. Of the strains, 25.9% were classified as Pen-Gs, 68.0% as Pen-Gir and 6.1% as Pen-Gr. The polymerase chain reaction product for wild-type pbp1a was found in 185 isolates, that for wild-type pbp2x was found in 66 isolates and that for wild-type pbp2b was found in 213 isolates. None of these three genes was detectable in 100 isolates while all of them were detected in 64 isolates (1aw/2xw/2bw). Of those 64 isolates with 1aw/2xw/2bw, the minimum inhibitory concentration (MIC) of PEN-G was < or =0.06 mg/l for 54 isolates and 0.12 mg/l for 10 isolates. Of the 272 strains for which the MIC of PAPM was < or =0.03 mg/l, there were 85 Pen-Gs, 184 Pen-Gir and three Pen-Gr isolates. Three strains for which the MIC of LVX was > or =4.0 mg/l included one Pen-Gs and two Pen-Gir isolates. The MICs of CLR correlated significantly with those of AZM. The MIC of CLR was > or =1 mg/l for 216 isolates, and the MIC of AZM was > or =1 mg/l for 244 of them. These data suggested that PAPM may be effective against S. pneumoniae infection, although acquisition of resistance should be considered. LVX also seemed to be effective against S. pneumoniae.

Topics: Aminoacyltransferases; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Carrier Proteins; Clarithromycin; Drug Resistance, Bacterial; Genes, Bacterial; Hexosyltransferases; Humans; In Vitro Techniques; Levofloxacin; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase; Mutation; Ofloxacin; Penicillin G; Penicillin Resistance; Penicillin-Binding Proteins; Peptidyl Transferases; Pneumococcal Infections; Streptococcus pneumoniae; Thienamycins

Community distribution of azithromycin has an important role to play in trachoma control. Previous studies have suggested that this may increase the prevalence of macrolide-resistant Streptococcus pneumoniae. S. pneumoniae was isolated from children under 7 years of age in Rombo District, northern Tanzania, before and 2 and 6 months after community-wide administration of azithromycin. Overall carriage rates were 11, 12, and 7%, respectively. Only one macrolide-resistant isolate carrying the mef gene was obtained 6 months after azithromycin administration. This contrasted with cotrimoxazole and penicillin resistance, both of which were common (cotrimoxazole resistance, 42, 43, and 47%, and penicillin resistance, 21, 17, and 16% at baseline, 2 months, and 6 months, respectively). There was a significant association between cotrimoxazole and penicillin resistance (P < 0.0001, Fisher's exact). These data suggest that in communities where macrolide resistance is rare, azithromycin distribution for trachoma control is unlikely to increase the prevalence of resistant organisms.

Topics: Anti-Bacterial Agents; Azithromycin; Carrier State; Child; Child, Preschool; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Penicillin Resistance; Pneumococcal Infections; Population Surveillance; Streptococcus pneumoniae; Trachoma

After absorption, azithromycin is concentrated intracellularly, with a correspondingly low serum concentration. A case of bacteriemia and meningitis caused by macrolide-sensitive Streptococcus pneumoniae during treatment with azithromycin is presented and discussed.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bacteremia; Drug Resistance, Bacterial; Female; Humans; Meningitis, Pneumococcal; Pneumococcal Infections; Streptococcus pneumoniae

The susceptibility of 4009 recent clinical isolates of Streptococcus pneumoniae to gatifloxacin, levofloxacin, ciprofloxacin, penicillin, ceftriaxone and azithromycin was determined. Overall rates of susceptibility to these agents were 99.4, 98.7, 71.2, 55.2, 80.9, and 71.3%, respectively. Resistance to all tested agents was associated with penicillin resistance. Of penicillin nonsusceptible isolates, 36% were resistant. Resistance to the fluoroquinolones was unusual and gatifloxacin generally appeared to be four-fold more active than levofloxacin or ciprofloxacin. Multidrug resistant S. pneumoniae accounted for 6.2% of this sample. The lowest rate of susceptibility to non-fluoroquinolone antibiotics was observed in isolates from the South region of the United States, which appeared to be explained by both the proportion of and the inherently higher MICs of certain types of isolates.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ceftriaxone; Child; Ciprofloxacin; Female; Fluoroquinolones; Gatifloxacin; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Ofloxacin; Penicillin Resistance; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae; United States

Topics: Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Bacterial; Respiratory Tract Infections; Streptococcus pneumoniae

Although changing patterns in antimicrobial resistance in Streptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniae antimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997-1998 and 1998-1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997-1998 were encountered in 1998-1999. This longitudinal surveillance study of resistance in S. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Microbial; Drug Resistance, Multiple; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Penicillins; Phenotype; Pneumococcal Infections; Population Surveillance; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bacteremia; Female; Humans; Meningitis, Pneumococcal; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Failure

The ability of the recently licensed 7-valent pneumococcal conjugate vaccine to cover isolates that cause otitis media, especially drug-resistant ones, was assessed using 500 recently obtained US isolates. Of these isolates, 418 (84%) belonged to vaccine-related serogroups, whereas 82 (16%) belonged to non-vaccine-related serogroups. Serotype 3 accounted for 48 (59%) of the non-vaccine-related serogroups. In addition, 93% of the isolates from patients < or =3 years of age belonged to serotypes that were included in or related to the heptavalent vaccine, compared with 49% of the isolates from older patients (P=.001). Most of the isolates (98%-100%) that were resistant to the antimicrobial agents tested were covered by the heptavalent vaccine, including 95.1% of the isolates from patients <2 years of age. The 7-valent pneumococcal conjugate vaccine could therefore potentially provide protection against all but 1 (type 3) of the common otitis media-associated pneumococcal serogroups identified in this study as well as against 98% of antibiotic-resistant isolates.

Topics: Adolescent; Adult; Aged; Amoxicillin; Azithromycin; Child; Child, Preschool; Clindamycin; Cross-Sectional Studies; Drug Resistance, Bacterial; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Meningococcal Vaccines; Microbial Sensitivity Tests; Middle Aged; Otitis Media; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae; Vaccines, Conjugate

Streptococcus pneumoniae strains have exhibited decreasing susceptibility to penicillins and macrolides during the past several years. We reviewed the medical charts of all patients with pneumococcal bacteremia who were admitted to a university hospital over a period of 1 year, to identify failures of outpatient therapy. Of 41 patients admitted with pneumococcal bacteremia, 4 had previously taken either azithromycin or clarithromycin for 3-5 days. All 4 had pneumococcal strains that exhibited low-level resistance to macrolide antibiotics. Among pneumococci, low-level resistance to macrolides can lead to clinical failure, and resistance to macrolides should be considered during the selection of empiric therapy for patients with presumed pneumococcal infections.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bacteremia; Child, Preschool; Clarithromycin; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Failure

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Microbial Sensitivity Tests; Pneumococcal Infections; Reagent Strips; Serum Bactericidal Test; Streptococcus pneumoniae

The in vitro activities of erythromycin, azithromycin, and clarithromycin against 178 clinical isolates from the lower respiratory tract of patients with chronic obstructive pulmonary disease were determined by an agar dilution method. The plates were incubated in air alone or in 5% carbon dioxide. The MICs measured in air alone were lower for most isolates than those measured in 5% carbon dioxide, illustrating the "pH effect" of incubation in carbon dioxide. Testing of isolates in 5% carbon dioxide on pH-adjusted medium (pH 8.4) resulted in MICs of one or two doubling dilutions lower than those obtained on agar with a neutral pH. A bioassay of the three agents incubated in air and in 5% carbon dioxide resulted in a significant loss of activity of all three agents in the carbon dioxide-enriched atmosphere. However, this loss-of-activity effect was significantly reduced when the bioassay medium was adjusted to pH 8.4 prior to incubation in 5% carbon dioxide.

Topics: Anti-Bacterial Agents; Azithromycin; Carbon Dioxide; Clarithromycin; Colony Count, Microbial; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Hydrogen-Ion Concentration; Lung Diseases, Obstructive; Microbial Sensitivity Tests; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Sputum; Streptococcus pneumoniae

Nasopharyngeal (NP) carriage of antibiotic-resistant Streptococcus pneumoniae was shown to be associated with recent antibiotic treatment. To date no studies have evaluated early dynamics of pneumococcal NP carriage during antibiotic treatment.. To observe changes in NP pneumococcal carriage within 3 to 4 days after initiation of antibiotic treatment in acute otitis media (AOM).. Patients ages 3 to 36 months with AOM treated with various antibiotics were prospectively followed. Nasopharyngeal culture for S. pneumoniae was obtained before (Day 1) and 72 to 96 h after initiation of treatment (Days 4 to 5). Antibiogram and serotyping were performed in all isolates as was also the MIC of penicillin. The disappearance and persistence of the initial isolates as well as the appearance of isolates with new serotype or with new antibiotic susceptibility patterns were investigated.. A total of 120 patients were studied: 106 received beta-lactam antibiotics and 14 received azithromycin. Among the initial 76 pneumococcal isolates 63, 37 and 13% were resistant to > or =1, > or =2 and > or =3 antibiotic drugs. After 3 to 4 days of treatment with various beta-lactam drugs, 45, 63 and 100% of isolates with MIC values of <0.1 microg/ml, 0.125 to 0.25 microg/ml and 0.38 to 1.0 microg/ml, respectively, persisted in the NP (P = 0.038). There was a difference between the various beta-lactam drugs in their effect on NP colonization: a drug with lower MIC values (cefuroxime-axetil) had a better eradication rate of penicillin-susceptible organisms than a less active one (cefaclor), but neither significantly reduced carriage of penicillin nonsusceptible isolates. Azithromycin eliminated carriage of macrolide-susceptible organisms but increased the carriage of macrolide-resistant ones. In 19 of 120 (16%) patients a new S. pneumoniae isolate was recovered 3 to 4 days after initiation of treatment. Of those 16 (84%) were resistant to the drug the patient was receiving.. A rapid selection of nonsusceptible NP pneumococcal isolates during antibiotic treatment for AOM is common. This phenomenon may contribute to the spread of resistant pneumococci.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Carrier State; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Lactams; Male; Microbial Sensitivity Tests; Nasopharynx; Otitis Media; Pneumococcal Infections; Prospective Studies; Streptococcus pneumoniae

We tested 83 penicillin-intermediate (Peni) and 50 penicillin-resistant (Penr) isolates of Streptococcus pneumoniae against eight oral antimicrobials. Clarithromycin's MICs (minimal inhibitory concentration) were generally the same or one to two dilutions less than those of azithromycin. Seventy-two percent of Peni isolates were susceptible to clarithromycin and azithromycin, in contrast to 42% and 40%, respectively, of Penr isolates. Cefuroxime activity exceeded that of cefprozil, which exceeded that of cefaclor, in Peni isolates. For all three cephalosporins, MICs of 90% of isolates tested were > or = 3 dilutions higher for Penr isolates than for Peni isolates. Percentages of Peni isolates susceptible to clindamycin and tetracycline were 92% and 83%, respectively, and 78% and 82% for Penr. Only 49% of Peni isolates and 4% of Penr isolates were susceptible to trimethoprim-sulfamethoxazole. Azithromycin, clarithromycin, cefuroxime, cefprozil, clindamycin, and tetracycline may be useful in treating infections caused by Peni S pneumoniae, but Penr isolates are frequently resistant to both old and newer agents.

Topics: Administration, Oral; Adult; Ambulatory Care; Anti-Bacterial Agents; Azithromycin; Cefaclor; Cefprozil; Cefuroxime; Cephalosporins; Child; Clarithromycin; Clindamycin; Culture Media; Humans; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

Azithromycin reaches high concentrations in phagocytic and other host cells, suggesting that they may transport this agent to specific sites of infection. Models of localized infection (Haemophilus influenzae middle ear infection in gerbils, Streptococcus pyogenes implanted contaminated paper disc and Streptococcus pneumoniae pneumonia in mice) that induced severe inflammatory response after challenge were used to explore this hypothesis. Animals were given a single 100 or 50 mg/kg po dose of azithromycin at various times from 2 to 120 h following introduction of a pathogen or sterile medium. When azithromycin was given during a period of little or no inflammation, there was marginal difference between concentrations found in infected or non-infected sites (bulla, disc, lung). However, when the compound was given during a period of inflammation, considerably higher drug concentrations were found in infected sites than in non-infected sites at 5-24 h after dosing (0.38-0.44 mg/c compared with 0.07-0.14 mg/L of bulla wash; 1.01-1.75 micrograms compared with < or = 0.01-0.03 microgram at the disc site; 1.72-5.28 mg/kg compared with 0.7-1.53 mg/kg of lung). When the observation periods were extended to include 48, 56 or 96 h after dosing, the ratio of azithromycin infection site concentration: serum concentration steadily increased with time in all model systems (middle ear, implanted disc and pneumonia), reflecting the maintenance of concentrations at the sites of infection, while serum concentrations declined. Bioassay of cell pellets and supernatants, obtained from pooled bulla washes of gerbils treated with azithromycin during a period of inflammation, revealed that cellular components accounted for about 75% of the azithromycin detected. These data show that increased azithromycin concentrations occur at sites of localized infection. This correlates with the presence of inflammation and is associated with the cellular components of the inflammatory response. Therefore, phagocytes may be important vehicles for delivering azithromycin to and sustaining azithromycin concentrations at sites of infection.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Blister; Female; Gerbillinae; Haemophilus Infections; Haemophilus influenzae; Lung; Male; Mice; Otitis Media; Phagocytes; Pneumococcal Infections; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

The prevalence of penicillin-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae in otitis media infections is increasing; emergence of these pathogens has complicated treatment.. To evaluate the incidence of penicillin resistance and the in vitro activity of amoxicillin/clavulanate, cefaclor, loracarbef, cefixime, trimethoprim/sulfamethoxazole, azithromycin and clarithromycin in S. pneumoniae isolates. The in vitro activity of azithromycin, clarithromycin and cefaclor was also evaluated in beta-lactamase-positive and -negative isolates of H. influenzae.. Bacterial isolates of S. pneumoniae and H. influenzae were obtained by tympanocentesis and subsequent culture of middle ear effusion from children with acute otitis media enrolled in a multicenter trial. Susceptibility to test agents was assessed by disk diffusion and broth dilution techniques with criteria established by the National Committee for Clinical Laboratory Standards.. Nineteen (31%) of the 61 S. pneumoniae isolates were resistant to penicillin. A significantly lower percentage of the S. pneumoniae isolates were resistant to azithromycin (16%) and clarithromycin (11%) than to penicillin, amoxicillin/ clavulanate, cefaclor, loracarbef or cefixime (31% in all cases). Azithromycin was also more active than cefaclor and significantly more active than clarithromycin against the 55 H. influenzae isolates.. The susceptibility of resistant and nonresistant strains of S. pneumoniae to azithromycin and clarithromycin and of isolates of H. influenzae to azithromycin, coupled with penetration of azithromycin into the middle ear, may provide a significant advantage in the treatment of otitis media.

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Child; Clarithromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Incidence; Microbial Sensitivity Tests; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Azithromycin; Bacteremia; Drug Resistance, Microbial; Female; Humans; Infant; Meningitis, Pneumococcal; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

Since serious sequelae may follow streptococcal infections, eradication is viewed as necessary for successful therapy. Studies were therefore conducted to compare the effectiveness of azithromycin with other macrolide antibiotics and amoxycillin to eliminate these organisms in experimental localized infections. In a Streptococcus pneumoniae lung infection induced by transtracheal challenge, the pathogen was not recovered after therapy with azithromycin (ED50 7.9 mg/kg), while clarithromycin was not effective (ED50 > 100 mg/kg). However, in a S. pneumoniae middle ear infection, azithromycin and clarithromycin were effective (ED50 2.9 and 6.3 mg/kg, respectively) in eradicating the pathogen from this closed space infection. Against a localized Streptococcus pyogenes infection (implanted inoculated disc), azithromycin effectively eradicated the pathogen, while clarithromycin, roxithromycin and erythromycin did not. Eradication of a viridans streptococcus or Streptococcus gordonii (formerly Streptococcus sanguis) from heart tissue in experimental bacterial endocarditis was also evaluated. Azithromycin given prophylactically or therapeutically was efficacious in eliminating the viridans streptococcus and S. gordonii in the bacterial endocarditis model of infection; erythromycin was only marginally effective in the same studies. All studies provided evidence of the bactericidal action of azithromycin in vivo and demonstrated the ability of the compound to eradicate streptococcal pathogens in localized infections.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Disease Models, Animal; Endocarditis, Bacterial; Erythromycin; Female; Gerbillinae; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Otitis Media; Pneumococcal Infections; Pneumonia; Rats; Roxithromycin; Streptococcal Infections; Streptococcus pyogenes