Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149514 (bronchitis)
 6,902 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptococcus pneumoniae has consistently become more resistant to primary, orally administered treatment regimens used for community-acquired respiratory tract infections (CARTI; sinusitis, bronchitis, pneumonia). As resistance rates approach 40-50% in the United States and North America for penicillin and macrolides, other agents also have exhibited coresistance rates of 10-20% (tetracycline, clindamycin, trimethoprim/sulfamethoxazole). These facts led to altered clinical treatment guidelines (IDSA) supporting the use of respiratory fluoroquinolones (levofloxacin, gatifloxacin, gemifloxacin, and moxifloxacin). This report from the SENTRY Antimicrobial Surveillance Program lists possible parenterally administered treatment alternatives for the fluoroquinolone (levofloxacin)-nonsusceptible pneumococci. The SENTRY Program isolates from CARTI (1997-2003), totaling 21605 strains from Europe, Asia Pacific, and the Americas, were screened for fluoroquinolone-resistant S. pneumoniae. A total of 157 (0.7%) levofloxacin-nonsusceptible (MIC > or = 4 microg/mL) strains were identified and tested by reference broth microdilution methods against 27 antimicrobials. Quinolone resistance-determining region (QRDR) mutations were determined by PCR amplification and gene sequencing. The entire population of S. pneumoniae had the following antibiogram demographics: penicillin-nonsusceptible (32%), macrolide resistance (24%), tetracycline resistance (21%), clindamycin resistance (11%), trimethoprim/sulfamethoxazole resistance (33%), and 6% of strains were resistant to all 5 drugs. Levofloxacin-resistant strains routinely had 2 or more QRDR mutations most frequently in gyrA at Ser81Phe or Tyr and in parC at Ser79Phe or Tyr and Lys137Asn. Four agents had extremely low rates of resistance when tested against the 157 levofloxacin-nonsusceptible strains (e.g., quinupristin/dalfopristin, 0% resistance; vancomycin, 0%; cefepime, 1%; ceftriaxone, 1%). Levofloxacin-nonsusceptible pneumococcal isolates remain uncommon, but are a growing problem in CARTI (1.4% in 2003), especially in previously fluoroquinolone-treated cases. Parenteral cephalosporins (cefepime or ceftriaxone) continue to be potent and safe for use in hospitalized patients with S. pneumoniae community-acquired pneumonia, used with or without co-drugs according to published guidelines.
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PMID:Therapeutic options among broad-spectrum beta-lactams for infections caused by levofloxacin-nonsusceptible Streptococcus pneumoniae. 1596 1

Levofloxacin (LEV) is a broad-spectrum fluoroquinolone used to treat pneumonia, urinary tract infections, chronic bacterial bronchitis, and prostatitis. Efflux transporters, primarily P-glycoprotein (P-gp), are involved in LEV's tissue penetration. In the present work, LEV free lung and prostate interstitial space fluid (ISF) concentrations were evaluated by microdialysis in Wistar rats after intravenous (i.v.) and intratracheal (i.t.) administration (7 mg/kg of body weight) with and without coadministration of the P-gp inhibitor tariquidar (TAR; 15 mg/kg administered i.v.). Plasma and tissue concentration/time profiles were evaluated by noncompartmental analysis (NCA) and population pharmacokinetics (popPK) analysis. The NCA showed significant differences in bioavailability (F) for the control group (0.4) and the TAR group (0.86) after i.t. administration. A four-compartment model simultaneously characterized total plasma and free lung (compartment 2) and prostate (compartment 3) ISF concentrations. Statistically significant differences in lung and prostate average ISF concentrations and levels of kidney active secretion in the TAR group from those measured for the control group (LEV alone) were observed. The estimated population means were as follows: volume of the central compartment (V1), 0.321 liters; total plasma clearance (CL), 0.220 liters/h; TAR plasma clearance (CLTAR), 0.180 liters/h. The intercompartmental distribution rate constants (K values) were as follows: K12, 8.826 h(-1); K21, 7.271 h(-1); K13, 0.047 h(-1); K31, 7.738 h(-1); K14, 0.908 h(-1); K41, 0.409 h(-1); K21 lung TAR (K21LTAR), 8.883 h(-1); K31 prostate TAR (K31PTAR), 4.377 h(-1). The presence of P-gp considerably impacted the active renal secretion of LEV but had only a minor impact on the efflux from the lung following intratracheal dosing. Our results strongly support the idea of a role of efflux transporters other than P-gp contributing to LEV's tissue penetration into the prostrate.
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PMID:Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration. 2662 23