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PubMed1992

Lomefloxacin and temafloxacin: two new fluoroquinolone antimicrobials.

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, safety, drug interactions, and dosage and administration of lomefloxacin and temafloxacin, two new antimicrobials, are presented. Lomefloxacin and temafloxacin exhibit activity comparable to that of ciprofloxacin against the Enterobacteriaceae. Lomefloxacin has only modest activity against common gram-positive organisms. Temafloxacin exhibits increased activity against the streptococci and moderate activity against many anaerobes, as compared with ciprofloxacin. Lomefloxacin and temafloxacin have only moderate antipseudomonal activity. Their elimination half-lives are 6-10 hours and they have good oral absorption, excellent penetration into many tissues and fluids, and a better drug-interaction profile than other similar agents. Lomefloxacin has demonstrated comparable efficacy to other therapies in the treatment of lower respiratory-tract infections and urinary-tract infections (UTIs) and for prophylaxis before surgical procedures in the urinary tract. Temafloxacin has been shown to be effective in the treatment of lower respiratory-tract infections, infections of the skin and associated structures, uncomplicated and complicated UTIs, bacterial prostatitis, and gonococcal and non-gonococcal urethritis and cervicitis. The most frequent adverse effects with lomefloxacin are gastrointestinal upset and headache; with temafloxacin, gastrointestinal complaints. Lomefloxacin's dosage is 400 mg p.o. daily for 10 days for treatment of acute bacterial exacerbations in chronic bronchitis or simple cystitis and for 14 days for treatment of complicated UTIs. Lomefloxacin is a new oral fluoroquinolone that is indicated for the treatment of various bacterial infections. Temafloxacin, another new fluoroquinolone, appeared to have some favourable characteristics but was withdrawn from the market.

Anti-Infective Agents↗
PubMed1992

[Proton pump inhibitors: their merits and demerits, and perspectives for future investigation].

Proton pump inhibitors have a potent antisecretory activity and are under development in many pharmaceutical companies. In this paper, the merits and demerits of the drugs, which have been revealed by experimental studies in humans and animals, are reviewed. Issues of the drugs which remain to be examined in the future are also discussed in reletion to their application in peptic ulcer patients. The issues include 1) genotoxicity of the drugs with long-term treatment; 2) their possible contribution to defensive factors of gastro-intestinal mucosa; 3) their antimicrobial activity against Helicobacter pylori; 4) interaction with the other drugs; etc.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMedDate not supplied

[Phthalazinilides. The action of ethyl bromopyruvate on phthalazine].

Our investigation for obtaining carbon-nitrogen stable ilides continued by the synthesis of new phthalazinic derivatives by the action of ethyl brompyruvate. The structure of the obtained products was confirmed by chemical and spectral analyses. The results regarding their antimicrobial action are also presented.

Anti-Bacterial Agents↗
PubMed1992

Do we need an intravenous fluoroquinolone?

Intravenous ciprofloxacin, the first parenteral fluoroquinolone available in this country, represents another class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Resistance emerges most often when quinolones are used to treat chronic infections or in patients with poorly drained abscesses, necrotic tissue, or indwelling catheters. Clinical trials have shown ciprofloxacin to be as effective as ceftazidime in the treatment of infections caused by gram-negative bacteria. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use. Ciprofloxacin inhibits the metabolism of theophylline, and morbidity and death have been reported in patients taking the two drugs concomitantly. Parenteral fluoroquinolones should be reserved for the treatment of gram-negative bacterial infections in patients in whom standard agents cannot be used.

Anti-Infective Agents↗
PubMed1992

Metronidazole.

Metronidazole has proven to be a useful and inexpensive antibiotic for the treatment of T. vaginalis and bacterial vaginosis. Few alternatives exist for these two specific indications, and metronidazole will continue to play a primary role in therapy. Oral metronidazole continues to be a very inexpensive alternative to oral vancomycin for the treatment of C. difficile-induced pseudomembranous colitis. For the treatment of moderate to severe mixed aerobic/anaerobic pelvic infections, metronidazole should be considered secondarily in patients who have failed other multiple- or single-drug regimens or in patients who are infected. with anaerobic organisms resistant to other commonly used agents including clindamycin, cefoxitin, cefotetan, or ampicillin/sulbactam. Metronidazole is not a first line drug of choice for antibiotic prophylaxis in obstetric and gynecologic patients.

Bacterial Infections↗
PubMed1992

Microbiologic profile of ceftibuten, a new oral cephalosporin.

The bactericidal activity of ceftibuten, alone and in combination with other drugs, has been assessed in vitro. The ability to induce a post-antibiotic effect (PAE), the rate of emergence of spontaneous resistant mutants, and the presence of Eagle's phenomenon were also investigated. Ceftibuten rapidly killed most Enterobacteriaceae, Haemophilus, Moraxella and Streptococcus species tested, including beta-lactamase-producing strains with over 90% cfu reduction after only 2 h. Using chequerboard and time-kill tests, ceftibuten was found to react synergistically with aminoglycosides, and to give an indifferent response with ofloxacin against a large number of Gram-negative aerobes and streptococci. Antagonism was never observed. Ceftibuten induced a PAE of approximately 1 h on S. pneumoniae. As expected, no PAE was observed with Gram-negative species. Spontaneous emergence of ceftibuten-resistant strains exposed to supra-MICs of the drug was rare (< or = 10(-8)) in all pathogens tested. No marked Eagle effect was detected when bacteria were treated with ceftibuten at concentrations exceeding 100-fold their MICs. This rules out the possibility that in vivo the high concentrations of ceftibuten reached in the urinary tract may hinder its excellent bactericidal activity.

Bacteria↗
PubMed1992

The role of the fluoroquinolones.

Over the past decade, the quinolone antimicrobial class has enjoyed a renaissance with the emergence of the fluoroquinolone subclass. Norfloxacin, ciprofloxacin, ofloxacin, enoxacin, and lomefloxacin have the advantages of broad antimicrobial activity profiles including gram-positive and -negative aerobes, favorable pharmacokinetic profiles including substantial oral bioavailability and extensive tissue distribution, and in general, favorable safety profiles. As clinical experience accumulates, our understanding of their optimum roles will become more refined. In six instances, these agents may be preferred over currently available agents: complicated urinary tract infections, empiric therapy of suspected bacterial gastroenteritis, eradication of the Salmonella carrier state, respiratory exacerbations due to Pseudomonas aeruginosa in patients with cystic fibrosis, invasive external otitis, and chronic gram-negative bacillary osteomyelitis. The efficacy and convenience of these agents for the treatment of a broad range of infections have already resulted in their extensive use. Such use carries the risk of selection pressure for the development of resistance and the adverse consequences of increased cost over less expensive, equally effective alternatives. The use of the fluoroquinolones should focus on infections where there is demonstrated benefit of these agents over conventional agents or infections for which there are few or no alternatives.

Anti-Infective Agents↗
PubMed1992

The new macrolides: expanding the ways in antibiotic treatment.

After almost forty years of its introduction, erythromycin will not be the exclusive member of the macrolide group of antibiotic agents, but a new generation of its derivatives which surpass it in pharmacological properties and clinical efficacy will also be available. Clarithromycin, a 14-membered derivative, has shown acid stability, longer half-life, lower protein binding and higher lung tissue penetration. Its exceedingly high activity against erythromycin-susceptible gram-positive cocci, Mycoplasma pneumoniae, and Legionella pneumophila makes it and important alternative choice in the therapy of respiratory tract infections. Also, it has shown high activity against Chlamydia trachomatis, and high urinary clearance of this unmetabolized molecule, important properties which would render it a special role in the treatment of genitourinary tract infections. Azithromycin, a 15-membered derivative has shown enhanced basicity (due to the nitrogen atom in its lactone ring), longer half-life and lower protein bindings. Its exceptional activity against Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Ureaplasma urealyticum and gram-negative bacteria, and its high concentration in tonsillar, pulmonary, prostatic and female reproductive tract tissues, assigns it an honorific place among the macrolides in the therapy against respiratory tract and genitourinary tract infections. Its role against T. gondii deserves further study, but points out this agent as a promise against this parasite.

Anti-Bacterial Agents↗
PubMed1992

[Drug resistance of Mycobacterium tuberculosis].

Drug resistance of Mycobacterium tuberculosis was followed up within a period of 1986 to 1989. There was a tendency to stabilization of resistance to streptomycin (42 per cent), tubazid (45.2 per cent) and ethionamide (up. to 1.4 per cent). Resistance to kanamycin slowly increased (by 3 to 6 per cent every year). Resistance to rifampicin markedly increased (almost 15 times). Resistance to ethambutol decreased (10 times). It was shown that the drug resistance could be lowered by using the drug combinations.

Antitubercular Agents↗
PubMed2003

[Antibiotic therapy in the elderly].

The management of antibiotherapy in elderly patients is a unique and challenging problem. Old patients often suffer more serious complications of infection, more serious adverse events and drug interaction with drug therapy. The choice of antibiotherapy must also take into account the evolution of bacterial ecology. About one third of persons older than 80 and a higher proportion of elderly disabled patients reside in long term care facilities. And now, bacterial flora in institutions remains intermediate between that of community acquired infections and the more antibiotic resistant hospital flora.

Adsorption↗
PubMed2004

The patient with an odontogenic infection.

The routine use of antibacterial agents for the management of odontogenic infections has not been shown to be effective and is inappropriate. Most of these bacterial infections can be resolved satisfactorily through an approach that incorporates debridement (primary dental care) in conjunction with local anesthesia. Odontogenic infections are polymicrobial. Facultative anaerobes, particularly viridans streptococci, accompanied by strict anaerobes, appear to predominate in all types of odontogenic infections. When antibacterial chemotherapy is indicated, the drug of choice should be either the most effective drug against the infective pathogens or the least toxic alternative among several available agents. It should also be emphasized that drugs seldom exert their beneficial effects without also causing adverse side effects. Dealing with this certainty, the clinician familiar with the mechanisms of action, principles of disposition, and therapeutic and adverse effects of antibacterial agents, has the advantage.

Anti-Bacterial Agents↗
PubMed1992

Vancomycin, metronidazole, and tetracyclines.

Over the last 30 years, the impurities in the vancomycin product have been reduced, perhaps resulting in a lower rate of adverse reactions. Vancomycin is bactericidal against most susceptible organisms, but is bacteriostatic against the enterococcus. Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus. Vancomycin attains good tissue and bone penetration and must be administered intravenously for systemic infections. It is eliminated renally with a half-life of about 6 hours; this half-life is prolonged with advanced age and reduced renal function. Significant adverse reactions can be minimized with careful attention to administration technique. Metronidazole has excellent tissue penetration; its antibacterial site of action is within anaerobic bacterial cells. Metronidazole is cleared by hepatic metabolism with a half-life of about 7 to 8 hours. The half-life is unchanged with renal dysfunction but is prolonged in patients with hepatic function impairment. Although adverse effects are relatively minor, there is an important interaction with warfarin. For podiatric infections, metronidazole can be used in skin- and soft-tissue infections; anaerobes in bone and joint infections are rare. Topical metronidazole has been used successfully in the treatment of decubitus ulcers, and this needs further evaluation. The most commonly used tetracyclines are tetracycline, doxycycline, and minocycline. The tetracyclines are broad spectrum antimicrobial agents, but their usefulness is limited by resistant strains. Tetracycline's absorption is significantly impaired by food, and it is cleared renally and fecally. Doxycycline has the highest protein binding and the longest half-life; it is cleared both renally and fecally without hepatic metabolism. Minocycline has the best absorption and tissue penetration; the unchanged drug is cleared renally and fecally, and it also undergoes hepatic metabolism. All tetracyclines have important adverse reactions with respect to teeth and bones, and they are contraindicated during pregnancy and for children under age eight.

Bacterial Infections↗
PubMed1992

Tuberculosis in the 1990's: resurgence, regimens, and resources.

Physicians in the United States must maintain vigilance for the 25,000 annual new cases of tuberculosis, concentrated in the elderly, in immigrants, in migrant and minority populations, and in immunosuppressed patients. Tuberculosis rates in the South remain above the national average. Physicians diagnosing tuberculosis may also treat the disease, working with health departments, which can assist with drugs, follow-up tests, and contact investigation. Powerful short-course regimens have been standard treatments since 1986. The preferred combination is isoniazid, rifampin, and pyrazinamide daily for 2 months, followed by isoniazid and rifampin for 4 more months. A 9-month regimen of isoniazid and rifampin is equally effective. Supplementation or extension of these regimens is mandatory when drug resistance or immunosuppression, respectively, is likely. Isoniazid prophylaxis for 6 to 12 months continues to be a vital but often neglected preventive measure for those infected with Mycobacterium tuberculosis, but without active disease.

Acquired Immunodeficiency Syndrome↗