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PubMed1991

Lack of emergence of significant resistance in vitro and in vivo to the new azalide antibiotic azithromycin.

In vitro experiments were performed in which 6 to 12 strains of Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae and Enterobacteriaceae were passaged nine times in sub-lethal concentrations of azithromycin or control antibiotics. Streptococcus pyogenes and Staphylococcus aureus quickly became resistant to rifampin as the MIC90 increased from 0.1 to greater than 50 micrograms/ml for both species. The MIC90 of azithromycin, erythromycin, amoxicillin and cefaclor increased by three dilutions for Staphylococcus aureus. The MIC values of azithromycin for Streptococcus pyogenes, Haemophilus influenzae and Enterobacteriaceae strains did not change significantly. However, for Haemophilus influenzae and the Enterobacteriaceae strains, the MIC values of erythromycin and oral cephalosporins increased four-fold. In the in vivo experiments, mice infected with Staphylococcus aureus or Escherichia coli contaminated sutures were administered azithromycin for three days, and on day 6 viable bacterial cells were recovered from the infection site. The sustained tissue concentrations of azithromycin indicated that the organisms would have been continuously exposed to azithromycin at the site of infection. Colonies isolated from azithromycin-treated and non-treated mice were cultured and their susceptibility to azithromycin compared. The azithromycin MIC values for Staphylococcus aureus cultures from treated and non-treated animals were identical. The azithromycin MICs for Escherichia coli recovered from treated animals were on average, less than one dilution higher than for control cultures. Emergence of significant resistance to azithromycin in the laboratory was not observed with the pathogens tested.

Animals↗

PubMed1984

The in vitro and in vivo activity of ciprofloxacin.

The antibacterial activity of ciprofloxacin (Bay o 9867) was compared with those of norfloxacin, nalidixic acid, trimethoprim-sulfamethoxazole, cefaclor, sisomicin and cefotaxime in in vitro and mouse protection studies. Approximately 300 clinical isolates of clinically important gram-positive and gram-negative species were used. The median MICs of ciprofloxacin against gram-positive and gram-negative bacteria ranged from less than or equal to 0.015-1 mg/l. Ciprofloxacin was 2-8 fold more active than norfloxacin and 100-fold more active than nalidixic acid. It also had a wider spectrum of activity against gram-positive organisms including even enterococci. No cross-resistance was observed between ciprofloxacin and beta-lactam antibiotics or aminoglycosides. Only acidic pH conditions decreased its activity. Ciprofloxacin showed rapid bactericidal action against organisms in both the logarithmic and stationary growth phases. In mouse protection studies (intraperitoneal infection) ciprofloxacin was significantly more effective than norfloxacin, ampicillin, trimethoprim-sulfamethoxazole, and also showed excellent activity against Pseudomonas infections.

Administration, Oral↗

PubMed1987

Comparative in vitro activity of the two new oral cephalosporin metabolites RO 19-5247 and RO 15-8074.

A total of 629 clinical strains of gram positive and gram negative bacteria were tested for their susceptibility to RO 19-5247, RO 15-8074, and other antimicrobial agents. Both RO 19-5247 and RO 15-8074 had good activity against strains of Enterobacteriaceae; however, resistance was found among some strains of Enterobacter, Citrobacter, Klebsiella and Morganella spp. Both compounds showed moderate to poor active against Acinetobacter spp., Pseudomonas aeruginosa, staphylococci and Streptococcus faecalis. Against strains of Haemophilus influenzae, Neisseria gonorrhoeae, Gardnerella vaginalis, Streptococcus pneumoniae and streptococci (not enterococci), each compound was highly active in vitro. RO 19-5247 and RO 15-8074 had comparable activity to cotrimoxazole, ceftazidime and ceftizoxime. Each new compound had considerably better activity then did cefaclor and amoxicillin/potassium clavulanate.

Cefmenoxime↗

PubMed1987

Comparative antibacterial activity of the new oral cephalosporin BMY-28100.

The in vitro activity of BMY-28100 was compared with that of four other oral cephalosporins against gram-positive cocci, Branhamella catarrhalis and Haemophilus influenzae. BMY-28100 showed 5-20 times better activity against staphylococci and streptococci. Methicillin-resistant staphylococci and enterococci were resistant to the drug. Branhamella catarrhalis and Haemophilus influenzae strains were moderately susceptible. Time-kill curve studies showed BMY-28100 to be equally as active as benzylpenicillin, amoxycillin, flucloxacillin and cefaclor. By virtue of its in vitro spectrum, BMY-28100 can be considered a potentially useful agent for treatment of respiratory tract infections.

Anti-Bacterial Agents↗

PubMed1987

In vitro activity of RO 15-8074 and RO 19-5247.

The in vitro activity of RO 15-8074 (cefetamet) and RO 19-5247, new oral cephalosporins, was compared with that of amoxicillin, cephalexin, cefaclor, cefuroxime and erythromycin against 292 clinical isolates using the agar dilution method. Both RO 15-8074 and RO 19-5247 were very active against Proteus mirabilis, Neisseria gonorrhoeae, Haemophilus influenzae and Streptococcus pyogenes, but less active against Staphylococcus saprophyticus and Enterobacter cloacae. RO 19-5247 was more active than RO 15-8074 against Haemophilus influenzae and Streptococcus viridans.

Amoxicillin↗

PubMed1987

Comparative in vitro activity of the new oral cephalosporin BMY-28100.

Using a broth microdilution method, the in vitro activity of BMY-28100 against 365 clinical strains of commonly isolated bacteria was determined. BMY-28100 showed good activity against streptococci, methicillin-susceptible staphylococci, Salmonella spp., Shigella spp., and beta-lactamase producing Branhamella catarrhalis and Haemophilus influenzae. Against susceptible strains of these organisms, BMY-28100 showed activity comparable to that of penicillin G, ampicillin, co-trimoxazole, erythromycin, cefaclor, doxycycline and amoxicillin/potassium clavulanate. BMY-28100 had moderate activity against Arizona hinshawii and poor activity against Campylobacter jejuni and Yersinia enterocolitica.

Anti-Bacterial Agents↗

PubMed1983

In vitro antibacterial activity of norfloxacin compared with eight other antimicrobial agents.

The antibacterial activity of norfloxacin, an organic acid structurally related to nalidixic acid, was compared with that of the oral cephalosporins cefaclor and cephalexin, and with that of nalidixic acid, cinoxacin, amikacin, ampicillin, trimethoprim alone and the combination of trimethoprim and sulfamethoxazole. Agar dilution studies were performed with a total of 398 clinical isolates of gram-negative bacteria. Norfloxacin was found to be the most active drug studied against each of the different groups of organisms tested. MIC90 values for norfloxacin were as follows: Citrobacter spp., 2 micrograms/ml; Enterobacter spp., 0.13 micrograms/ml; Escherichia coli, 0.06 micrograms/ml; Klebsiella spp., 0.13 micrograms/ml; Proteus spp., 0.06 micrograms/ml; Salmonella spp., 1 microgram/ml; Serratia spp., 0.13 micrograms/ml; and Pseudomonas spp., 2 micrograms/ml. MIC90 values for the other drugs were 4 micrograms/ml or greater and many organisms were totally resistant to one or more of the other drugs (MIC greater than 128 micrograms/ml). Cross resistance between norfloxacin and the related drugs nalidixic acid and cinoxacin was not observed.

Anti-Bacterial Agents↗

PubMed1987

In vitro activity of BMY 28100, a new oral cephalosporin.

BMY 28100, a new oral cephalosporin, demonstrated good in vitro activity against common gram-positive and gram-negative respiratory and urinary tract pathogens. Its activity was shown by microdilution techniques to be generally higher than those of ampicillin, cephalothin and cephalexin, but comparable to those of cefaclor and, except for Haemophilus spp. and Branhamella spp., to amoxicillin/clavulanate.

Bacteria↗

PubMed1990

Comparative in vitro activity of the new oral cephalosporin Bay v 3522 against aerobic and anaerobic bacteria.

The in vitro activity of the new oral cephalosporin Bay v 3522 against 229 aerobic and 330 anaerobic clinical isolates was determined using the agar dilution technique. For comparison, amoxicillin, amoxicillin/clavulanate, cefaclor, cefadroxil, cefuroxime, cephalexin, ciprofloxacin, clindamycin, co-trimoxazole, doxycycline, erythromycin and metronidazole (only anaerobic bacteria) were tested. Bay v 3522 was found to have high activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, anaerobic cocci, Propionibacterium acnes, Clostridium perfringens and fusobacteria. When tested against a higher inoculum or using the broth dilution technique, the activity of Bay v 3522 showed little dependence on inoculum size and the bactericidal activity was similar to inhibitory activity in most bacterial groups. Bay v 3522 may be useful in the treatment of skin, soft tissue and respiratory tract infections. Clinical studies are thus warranted.

Aminoglycosides↗

PubMed2001

Antibiotic susceptibilities among recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis from fifteen countries.

Between July 1998 and July 1999, 3,060 Haemophilus influenzae and 1,486 Moraxella catarrhalis strains were isolated in 31 centers in 15 countries in order to determine their antimicrobial susceptibilities and the presence of beta-lactamase production in Haemophilus influenzae. Overall 17.1% of the Haemophilus influenzae isolates were beta-lactamase positive, while more than 95% were susceptible to amoxicillin/clavulanate, cefaclor, loracarbef, cefuroxime, azithromycin and ciprofloxacin. Eleven (0.3%) isolates were beta-lactamase positive and ampicillin resistant and 7 (0.2%) isolates were ciprofloxacin resistant. The minimum inhibitory concentrations for 90% of the isolates tested were lowest for ciprofloxacin (0.03) and highest for cefprozil (8) against Moraxella catarrhalis.

Anti-Bacterial Agents↗

PubMed2002

Trends in antimicrobial susceptibility of the Streptococcus milleri group.

A collection of 114 clinical Streptococcus milleri group (SMG) strains at the Ryukyu University Hospital obtained in 1999 and 2000, was identified and tested for susceptibility to 12 antibiotics. The percentage of strains with intermediate susceptibility to penicillin G was relatively high (14%). Cefaclor and cefotiam, with a MIC 90 of 2 microg/ml, were less active than cefotaxime. Strains nonsusceptible to erythromycin, clindamycin, and azithromycin were found with a frequency of 8%, 5%, and 4%, respectively. Almost all of the SMG strains were susceptible to fluoroquinolones (except for 1% of the strains nonsusceptible to levofloxacin), and sitafloxacin (DU-6859a) was the most active agent among the 12 tested antibiotics.

Anti-Bacterial Agents↗

PubMed2002

Susceptibility change to antibiotics of Staphylococcus aureus strains isolated from skin infections between July 1994 and November 2000.

We measured the in-vitro susceptibility of 833 Staphylococcus aureus strains, isolated from skin infections at our hospital between July 1994 and November 2000, to 13 antimicrobial agents (ampicillin, methicillin, cephalexin, cefaclor, cefpodoxime proxetil, gentamicin, erythromycin, clindamycin, minocycline, vancomycin, fusidic acid, ofloxacin, and nadifloxacin). The concentrations required to inhibit 50% of the strains (MIC(50)) of all these antimicrobial agents was extremely stable and ranged at levels below 3.13 microg/ml, except for gentamicin; in contrast, the MIC(90) was not uniform. The MIC(90) of vancomycin, fusidic acid, and nadifloxacin was very low and stable. No strain was resistant to vancomycin. The incidence of MRSA was 10%-20%.

Humans↗

PubMed2002

The fecal microflora of 1-3-month-old infants during treatment with eight oral antibiotics.

We examined the fecal microflora of 1-3-month-old infants during treatment with phenoxymethylpenicillin, amoxycillin, pivampicillin, cefaclor, cefadroxil, loracarbef, erythromycin or cotrimoxazole. Escherichia coli increased during treatment with penicillins or cephalosporins, but was not affected by erythromycin or cotrimoxazole. Other enterobacteria were acquired or increased during treatment with all agents except cotrimoxazole. Enterococci persisted or increased during phenoxymethylpenicillin, cephalosporin or cotrimoxazole treatment, whereas erythromycin and the other penicillins suppressed them. Bacteroides, bifidobacteria and lactobacilli were suppressed to undetectable levels in most infants during treatment with all agents, except phenoxymethylpenicillin and loracarbef.

Bacterial Infections↗

PubMed1999

Antimicrobial susceptibility of 1,422 Haemophilus influenzae isolates from respiratory tract infections in Spain. Results of a 1-year (1996-97) multicenter surveillance study. Spanish Surveillance Group for Respiratory Pathogens.

A Haemophilus influenzae multicenter antimicrobial susceptibility surveillance was carried out. An overall beta-lactamase production rate of 25.7% was found, with significant differences between hospitals ranging between 7.9 and 47.9%. Presumable intrinsic resistance was found in 4.6% of strains. No differences in susceptibility were observed between beta-lactamase positive and beta-lactamase negative strains for all antibiotics, except for penicillin, amoxicillin and cefaclor. A higher prevalence of resistance was found for clarithromycin vs azithromycin (22.6 vs 0.7%). Differences in all these factors make surveillance essential as a guideline for empiric treatment in community-acquired respiratory tract infections.

Drug Resistance, Microbial↗

PubMed1991

Use of quinolones for the treatment of acute exacerbations of chronic bronchitis.

The availability of a new generation of quinolones expands the choices of antimicrobials for therapy of acute exacerbations of chronic bronchitis. These agents have broad antimicrobial activity, including good in vitro activity against respiratory pathogens, and advantageous pharmacokinetic characteristics, including bronchial tissue penetration. Ciprofloxacin, enoxacin, ofloxacin, and temafloxacin have been evaluated in a number of clinical trials, compared to the reference agents ampicillin, amoxicillin (with and without clavulanate), cefaclor, doxycycline, and erythromycin. Ciprofloxacin, ofloxacin, and temafloxacin have generally demonstrated greater clinical success than enoxacin. While these agents are effective against many respiratory pathogens, Streptococcus pneumoniae and Pseudomonas aeruginosa infections appear to pose problems. Temafloxacin and ciprofloxacin have been compared; temafloxacin eradicated S. pneumoniae more efficiently and did not interact with theophylline. Fluoroquinolones are an important addition to the agents useful for bacterial exacerbations of chronic bronchitis.

Acute Disease↗

PubMed1992

The U.S. clinical experience with lomefloxacin, a new once-daily fluoroquinolone.

Lomefloxacin is a new fluoroquinolone antimicrobial agent that has undergone extensive worldwide clinical evaluation. This report summarizes the safety and efficacy of lomefloxacin in the treatment of uncomplicated urinary tract infections, complicated urinary tract infections, acute exacerbations of chronic bronchitis, and for prophylaxis during urinary tract surgery. The clinical data presented are an overview of all clinical studies conducted in the United States to date. The results have been derived from multiple studies in which patients received lomefloxacin or a comparative agent in either blinded or open-label studies. During the course of the clinical program in the United States, lomefloxacin has been compared with oral norfloxacin, ciprofloxacin, and cefaclor, as well as parenteral cefotaxime. In all instances, the once-daily oral administration of lomefloxacin was either equally effective or statistically significantly superior in clinical and/or bacteriologic efficacy to these comparative agents. In addition, the comparators were administered either two or three times per day, except in the surgical prophylaxis studies, in which single doses of each antibiotic were administered preoperatively. These results attest to the value of the convenience and simplicity of the oral dosing regimen for lomefloxacin. During the course of the clinical program, lomefloxacin was well tolerated, with most adverse events of mild to moderate severity. In general, the incidence of adverse events for patients and subjects receiving lomefloxacin was comparable to that observed in patients treated with comparator drugs. The most common adverse events were related to the gastrointestinal tract (nausea and diarrhea), the skin and appendages (photosensitivity), and the central nervous system (dizziness and headache). A sub-analysis of adverse events in the respiratory studies demonstrated that concomitant administration of lomefloxacin and theophylline does not increase the incidence of adverse events when compared to lomefloxacin alone. An additional sub-analysis also showed that the incidence of adverse events in elderly patients was similar to that in younger patients. The results of the U.S. clinical program indicate that lomefloxacin administered orally once daily is effective and well tolerated in a variety of infections of bacterial origin.

Anti-Infective Agents↗

PubMed1992

In vitro activity of loracarbef and effects of susceptibility test methods.

Loracarbef is a new oral antimicrobial of the carbacephem class with in vitro activity against the common pathogens associated with skin infections, otitis media, sinusitis, bronchopulmonary infections, and urinary tract infections. A review of the literature shows the following ranges for 90% minimum inhibitory concentration (MIC90) values (microgram/mL) against the organisms that commonly cause these illnesses: Streptococcus pneumoniae, 0.25-2.0; Moraxella (Branhamella) catarrhalis (beta-lactamase positive), 0.5-8.0; M. catarrhalis (beta-lactamase negative), 0.12-0.25; Haemophilus influenzae (beta-lactamase positive), 0.5-16.0; H. influenzae (beta-lactamase negative), 0.25-8.0; Escherichia coli, 2.0-25; Klebsiella pneumoniae, 0.25-8.0; Proteus mirabilis, 1.0-8.0; Streptococcus pyogenes, less than or equal to 0.06-1.0; Staphylococcus aureus (beta-lactamase positive), 8.0; S. aureus (beta-lactamase negative), 1.0-2.0. The in vitro activity of loracarbef against these common outpatient pathogens is similar to that of other oral antimicrobials such as cefaclor, cefuroxime axetil, cefixime, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole. The results of in vitro susceptibility tests with any antimicrobial, including loracarbef, are somewhat dependent on the specific test method that is employed in the laboratory. This is particularly true with H. influenzae. Furthermore, the results of loracarbef susceptibility tests are of uncertain value in predicting therapeutic outcome.

Cephalosporins↗

PubMed1986

Therapeutic consequences of drug interactions with theophylline pharmacokinetics.

Elimination of theophylline from the body occurs mainly (approximately 90%) by biotransformation, followed by excretion of the metabolites. Consequently, drugs affecting microsomal enzyme systems in the liver may alter the elimination of theophylline. Since theophylline has a rather narrow therapeutic window, dose adjustment might be necessary. Of the sympathomimetics, isoproterenol reduces theophylline clearance by 25%, but metaproterenol and terbutaline do not. Of the antibiotics, erythromycin and troleandomycin decrease theophylline clearance by 25% and 50%, respectively. No effect was observed with tetracycline, doxycycline, amoxicillin, cefaclor, and co-trimoxazole. On the other hand, rifampin (antituberculotic agent) increases theophylline clearance by 30%. Corticosteroids (hydrocortisone, methylprednisolone, and prednisone) do not affect theophylline kinetics. Influenza vaccination also has no influence. The antiulcerative agent (H2 antagonist) cimetidine decreases theophylline clearance by 30%, but the agent ranitidine does not have any effect. Oral contraceptives may decrease theophylline elimination by 30%. Barbiturates and phenytoin may enhance theophylline clearance substantially (up to 75%). If an interaction is expected, careful monitoring of theophylline plasma concentrations is required to optimize the dose.

Adrenal Cortex Hormones↗