minocycline and Pneumococcal-Infections

Tigecycline (TGC), a glycylcycline, has expanded activity against Gram-positive and Gram-negative, anaerobic, and atypical bacteria. Two phase 3 studies were conducted. Hospitalized patients with community-acquired pneumonia (CAP) were randomized to intravenous (IV) TGC (100 mg followed by 50 mg bid) or IV levofloxacin (LEV) (500 mg bid). In 1 study, patients could be switched to oral LEV after at least 3 days intravenously. The coprimary efficacy end points were as follows: clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). The secondary end points were as follows: microbiologic efficacy and susceptibility to TGC for CAP bacteria. Safety evaluations were included. Eight hundred ninety-one were patients screened: 846 mITT (TGC 424, LEV 422), 574 CE (TGC 282, LEV 292). Most patients had Fine Pneumonia Severity Index II to IV (80.7% TGC, 74.4% LEV, mITT). At TOC (CE), TGC cured 253/282 patients (89.7%) and LEV cured 252/292 patients (86.3%); the absolute difference of TGC-LEV was 3.4% (95% confidence interval [CI], -2.2 to 9.1, noninferior [P < 0.001]). In c-mITT, TGC cured 319/394 patients (81.0%) and LEV cured 321/403 patients (79.7%); the absolute difference of TGC-LEV was 1.3% (95% CI -4.5 to 7.1, noninferior [P < 0.001]). The drug-related adverse events (AEs) of nausea (20.8% TGC versus 6.6% LEV) and vomiting (13.2% TGC versus 3.3% LEV) were significantly higher in TGC; elevated alanine aminotransferase (2.8% TGC versus 7.3% LEV) and aspartate aminotransferase (2.6% TGC versus 6.9% LEV) were significantly higher in LEV. Discontinuations for AEs were low (TGC, 26 patients [6.1%]; LEV, 34 patients [8.1%]). TGC appeared safe and achieved cure rates similar to LEV in hospitalized patients with CAP.

Topics: Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Female; Gram-Negative Bacterial Infections; Haemophilus Infections; Humans; Levofloxacin; Liver Function Tests; Male; Middle Aged; Minocycline; Ofloxacin; Pneumococcal Infections; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

A group of 41 patients, all admitted to hospital because of acute purulent exacerbations of chronic respiratory disease, were treated with either doxycycline or minocycline in a double-blind randomized study. Drug dosage was one 100 mg capsule twice daily for seven days. Bacteriological and clinical assessment before and immediately after treatment showed no significant differences between the doxycycline and the minocycline groups, nor did further evaluation after seven days follow-up. Pharmacokinetic studies showed that the Cmax and 0-11 h AUC values in blood were higher for doxycycline, whereas the sputum Cmax was, on average, higher for minocycline because of the greater penetration of the latter. The MIC values for the two antibiotics differed slightly, usually, but not always, in favour of minocycline. Problems were experienced with both agents in the eradication of Haemophilus influenzae. The net clinical results with the two drugs were identical.

Topics: Adult; Bacterial Infections; Bronchitis; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Doxycycline; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Microbial Sensitivity Tests; Minocycline; Moraxella catarrhalis; Pneumococcal Infections; Random Allocation; Streptococcus pneumoniae; Tetracyclines

We report here on 14438 Streptococcus pneumoniae and 14770 Haemophilus influenzae isolates collected from 560 centres globally between 2004 and 2012 as a part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.).. MIC testing was performed using broth microdilution methods as described by the Clinical and Laboratory Standards Institute (CLSI) using CLSI-approved breakpoints; US Food and Drug Administration breakpoints were used for tigecycline as CLSI breakpoints are not available.. At least 99% of S. pneumoniae isolates globally were susceptible to levofloxacin, linezolid, tigecycline or vancomycin. Penicillin resistance was observed among 14.8% of S. pneumoniae and was highest in Asia/Pacific Rim (30.1%) and Africa (27.6%); 23.4% of S. pneumoniae isolates were penicillin-intermediate, which were most common in Africa (37.6%). Minocycline susceptibility among S. pneumoniae decreased by 20% between 2004-2008 and 2009-2012. High (>98.5%) susceptibility was reported among H. influenzae to all antimicrobial agents on the T.E.S.T. panel excluding ampicillin, to which only 78.3% were susceptible. β-lactamase production was observed among 20.2% of H. influenzae isolates; 1.5% of isolates were β-lactamase negative, ampicillin-resistant.. S. pneumoniae remained highly susceptible to levofloxacin, linezolid, tigecycline and vancomycin while H. influenzae was susceptible to most antimicrobial agents in the testing panel (excluding ampicillin).

Topics: Anti-Bacterial Agents; Global Health; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Minocycline; Pneumococcal Infections; Streptococcus pneumoniae; Tigecycline

Isolates of Streptococcus pneumoniae (n = 530) were collected from 20 hospitals in different parts of Taiwan from 2006 to 2010. MICs to 16 antimicrobial agents were determined by broth dilution method and serotypes were identified by latex agglutination. Based on meningitis (non-meningitis) criteria established by the CLSI, 11.7% (63.2%) of all isolates were susceptible to penicillin and 46.0% (83.8%) were susceptible to ceftriaxone. Of the isolates, 94.3% were non-susceptible to azithromycin and 5.8% and 7.2% were non-susceptible to moxifloxacin and levofloxacin, respectively. Susceptibility to penicillin by meningitis criteria increased significantly (P = 0.0012) with year, and that to clindamycin and amoxicillin/clavulanic acid declined significantly (P < 0.05). Six major serotypes were found, namely 19F (24.0%), 23F (18.5%), 14 (13.6%), 6B (12.5%), 19A (7.5%) and 3 (5.1%). Prevalence of serotypes 19F and 14 remained stationary, that of serotype 6B decreased significantly (P < 0.0001) and that of serotype 19A increased significantly (P < 0.0001) with year. The coverage rate of PCV-7 among the pneumococcal isolates declined from 80.5% in 2006 to 50% in 2010 (P < 0.0001) and that of PCV-13 declined from 91.5% in 2009 to 75% in 2010. The non-susceptibility rate to levofloxacin was highest among serotype 23F isolates (13.3%) and lowest among serotype 19A isolates (2.5%). Rates of resistance to the four agents penicillin, ceftriaxone, azithromycin and clindamycin were highest among serotype 19A isolates (70.0%) and 23F isolates (49.0%). All serotype 3 isolates were susceptible to four of the most commonly used antibiotics (penicillin, ceftriaxone, azithromycin and levofloxacin).

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Epidemiological Monitoring; Heptavalent Pneumococcal Conjugate Vaccine; Hospitals; Humans; Latex Fixation Tests; Microbial Sensitivity Tests; Minocycline; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae; Taiwan; Tigecycline

We report here on the in vitro activity of tigecycline and comparators against a global collection of Streptococcus pneumoniae and Haemophilus influenzae collected between 2004 and 2008 as part of the Tigecycline Evaluation and Surveillance Trial. A total of 6785 S. pneumoniae and 6642 H. influenzae isolates were collected, most from North America. The percentages of penicillin-intermediate resistance and penicillin resistance among S. pneumoniae in North America were 27.8% and 14.3%, respectively. Penicillin resistance ranged from 9.3% in Europe to 25.1% in the Asia-Pacific Rim. The rate of beta-lactamase-producing H. influenzae was 25.8% in North America, and among the other regions, it ranged from 8.7% in South Africa to 26.8% in the Asia-Pacific Rim. Tigecycline MIC(90)'s were 0.03 to 0.12 mg/L and 0.5 to 2 mg/L, depending on the region considered, against S. pneumoniae and H. influenzae, respectively. Tigecycline had low MIC(90)'s against S. pneumoniae and H. influenzae, irrespective of resistance to beta-lactams.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Asia; Bacterial Proteins; beta-Lactamases; Child; Child, Preschool; Europe; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; North America; Penicillin Resistance; Pneumococcal Infections; South Africa; Streptococcus pneumoniae; Tigecycline; Young Adult

Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), can be aggravated by a mild Streptococcus pneumoniae infection. This study was performed to assess whether treatment with antibiotics inhibiting bacterial protein synthesis reduces the detrimental effect of infection on the course of EAE.. In vitro, release of proinflammatory pneumococcal products was studied by enzyme immunoassay and western blot. Seven days after induction of EAE (prior to the onset of symptoms) mice were infected intraperitoneally with S. pneumoniae and treated either with the inhibitors of bacterial protein synthesis minocycline or rifampicin, or with the beta-lactam ceftriaxone.. During bacterial killing in vitro, minocycline and rifampicin released lower quantities of proinflammatory bacterial products from S. pneumoniae than ceftriaxone. Mice treated with minocycline developed symptoms of EAE 1 day later than mice treated with ceftriaxone. Neither minocycline nor rifampicin therapy, however, reduced the severity of EAE in comparison with ceftriaxone treatment.. Although statistically significant (P = 0.04), a delay of 1 day in the onset of symptoms of EAE after minocycline treatment is of minor clinical relevance. These data do not support the hypothesis of superiority of a bacterial protein synthesis inhibitor over a beta-lactam antibiotic for the treatment of concomitant infections during the latent phase of EAE or MS.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Encephalomyelitis, Autoimmune, Experimental; Female; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Minocycline; Pneumococcal Infections; Rifampin; Teichoic Acids

A total of 6,991 unique patient isolates of Streptococcus pneumoniae were collected from October 1997 to June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among these isolates, 20.2% were penicillin nonsusceptible, with 14.6% being penicillin intermediate (MIC, 0.12 to 1 microg/ml) and 5.6% being penicillin resistant (MIC, > or =2 microg/ml). The proportion of high-level penicillin-resistant S. pneumoniae isolates increased from 2.4 to 13.8% over the last 3 years of the study, and the proportion of multidrug-resistant S. pneumoniae isolates increased from 2.7 to 8.8% over the 5-year period. Resistant rates (intermediate and resistant) among non-beta-lactam agents were as follows: macrolides, 9.6 to 9.9%; clindamycin, 3.8%; doxycycline, 5.5%; chloramphenicol, 3.9%; and trimethoprim-sulfamethoxazole, 19.0%. Rates of resistance to non-beta-lactam agents were higher among penicillin-resistant strains than among penicillin-susceptible strains. No resistance to vancomycin or linezolid was observed; however, 0.1% intermediate resistance to quinupristin-dalfopristin was observed. The rate of macrolide resistance (intermediate and resistant) increased from 7.9 to 11.1% over the 5 years. For the fluoroquinolones, the order of activity based on the MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s was gemifloxacin > clinafloxacin > trovafloxacin > moxifloxacin > grepafloxacin > gatifloxacin > levofloxacin > ciprofloxacin. The investigational compounds ABT-773 (MIC(90), 0.008 microg/ml), ABT-492 (MIC(90), 0.015 microg/ml), GAR-936 (tigecycline; MIC(90), 0.06 microg/ml), and BMS284756 (garenoxacin; MIC(90), 0.06 micro g/ml) displayed excellent activities. Despite decreases in the rates of antibiotic consumption in Canada over the 5-year period, the rates of both high-level penicillin-resistant and multidrug-resistant S. pneumoniae isolates are increasing in Canada.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Canada; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Fluoroquinolones; Humans; Indoles; Ketolides; Longitudinal Studies; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumococcal Infections; Quinolones; Respiratory Tract Infections; Streptococcus pneumoniae; Tigecycline

Topics: Carrier State; Cross Infection; Demeclocycline; Doxycycline; Drug Resistance, Microbial; Humans; Lincomycin; Microbial Sensitivity Tests; Minocycline; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Tetracycline

Topics: Adolescent; Child; Child, Preschool; Female; Furunculosis; Humans; Infant; Male; Microbial Sensitivity Tests; Minocycline; Otitis Media; Otorhinolaryngologic Diseases; Pneumococcal Infections; Staphylococcal Infections; Streptococcal Infections; Tetracycline; Tonsillitis