Postantibiotic suppression of growth of erythromycin A-susceptible and -resistant gram-positive bacteria by the ketolides telithromycin (HMR 3647) and HMR 3004.

We investigated the in vitro postantibiotic effects (PAEs) of the ketolides telithromycin (HMR 3647) and HMR 3004 and analyzed the results using the sigmoid E(max) model. Mean maximum telithromycin PAEs against erythromycin A-susceptible strains of Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae were 3. 7, 8.

Pharmacokinetics and pharmacodynamics of fluoroquinolones.

The fluoroquinolones have moderate to excellent bioavailability, moderate to long elimination half-lives (50 to 98%) and volumes of distribution >1.5 L/kg. There is considerable variation in elimination pattern between fluoroquinolone agents, ranging from predominant renal excretion to extensive hepatic metabolism.

Fusidic acid in vitro activity.

Fusidic acid is a narrow spectrum agent that acts to inhibit protein synthesis by inhibition of elongation factor G at the level of the ribosome. Because of high protein binding susceptibility testing in vitro is affected by the presence of blood or serum. In addition, there is a modest inoculum effect in vitro.

Resistance to fusidic acid.

Resistance to fusidic acid is determined by a number of mechanisms. The best described are alterations in elongation factor G, which appear in natural mutants that are harboured at low rates in normal populations of staphylococci (10(6) to 10(8)). Altered drug permeability has also been described, and appears to be plasmid-borne.

Fusidic acid pharmacology, pharmacokinetics and pharmacodynamics.

Fusidic acid comes in a variety of formulations for oral, intravenous and topical use. After oral administration of 500 mg Cmax values range from 14.5-3.

The clinical efficacy of continuous-infusion flucloxacillin in serious staphylococcal sepsis.

Since the efficacy of beta-lactams against pathogens such as methicillin-susceptible Staphylococcus aureus (MSSA) is related to the time for which serum drug concentrations exceed the MIC for the pathogen, administration of anti-staphylococcal beta-lactams by continuous infusion may provide a more suitable means of drug delivery than intermittent dosing. To assess the clinical efficacy of continuous-infusion therapy, we reviewed the outcomes for 20 consecutive patients with proven serious MSSA sepsis (three with endocarditis, ten osteomyelitis, one endocarditis plus osteomyelitis and six deep abscess) treated with continuous-infusion flucloxacillin (8-12 g/day). Patients initially receiving routine intermittent-dose flucloxacillin therapy were changed to continuous-infusion flucloxacillin (mean duration 29 days; range 4-60 days) for completion of their treatment course.

Rapidly emerging antimicrobial resistances in Streptococcus pneumoniae in Australia. Pneumococcal Study Group.

Objective: To examine the prevalence of resistance in Streptococcus pneumoniae to key antimicrobials in Australia during 1997.

Design: Prospective, Australia-wide, laboratory-based survey.

Setting: 11 microbiology laboratories from seven Australian States and Territories (five private laboratories and six public hospital laboratories) between March and November 1997.

Home-based treatment of cellulitis with twice-daily cefazolin.

Objective: To assess the clinical outcome and pharmacokinetics of therapy with cefazolin for patients with cellulitis in a hospital-in-the-home (HIH) program.

Design: Observational study with outcome data compared with previously published reports of therapy for cellulitis.

Setting: A university teaching hospital and HIH unit, July 1996-December 1997.

Emergence and epidemiology of vancomycin-resistant enterococci in Australia.

Enterococci with acquired resistance to vancomycin and other glycopeptides (VRE) have emerged and spread rapidly through Europe and the United States since 1988. The first isolate of VRE in Australia occurred in 1994. Only one case was noted in 1995.

The pharmacodynamics of beta-lactams.

Considerable information on the pharmacodynamics of beta-lactams has accumulated in the past 20 years. In vitro, beta-lactams demonstrate time-dependent killing and variable postantibiotic effects. Animal models have shown that the time for which drug levels exceed the minimum inhibitory concentration (MIC) correlates best with bacterial eradication, and this is now being borne out in human studies.

Emergence of vancomycin-resistant enterococci in Australia: phenotypic and genotypic characteristics of isolates.

Enterococci with resistance to glycopeptides have recently emerged in Australia. We developed multiplex PCR assays for vanA, vanB, vanC1, and vanC2 or vanC3 in order to examine the genetic basis for vancomycin resistance in Australian isolates of vancomycin-resistant Enterococcus faecium and E. faecalis (VRE).

Antimicrobial resistance testing of Helicobacter pylori: a comparison of Etest and disk diffusion methods.

Routine antimicrobial resistance testing of Helicobacter pylori is more commonly performed since the correlation between metronidazole resistance and failure to eradicate using this drug, has been made. While resistance testing of H. pylori by Etest is simple to perform, it is expensive compared to disk diffusion methods.

Neurological complications of chlamydial infections: case report and review.

We describe a patient with Chlamydia pneumoniae infection who presented with cerebellar dysfunction, followed by respiratory failure requiring mechanical ventilation. C. pneumoniae is an important respiratory pathogen, and other clinical manifestations, including neurological syndromes, are being increasingly recognized.

The postantibiotic effect of fusidic acid against gram-positive bacteria.

The in-vitro postantibiotic effect (PAE) of fusidic acid was tested for six strains of Staphylococcus aureus and four strains of Streptococcus pyogenes. The maximum PAE that could be achieved was more than 3 h, but at concentrations of antibiotic attainable in humans, the PAE was less than 2 h. Additional experiments were performed in albumin, to examine the effect of the strong protein binding of fusidic acid on the MIC and PAE.

The postantibiotic effect of imipenem: relationship with drug concentration, duration of exposure, and MIC.

The postantibiotic effect (PAE) of imipenem against Escherichia coli was measured at a wide variety of drug concentrations and times of exposure. We observed that the area under the concentration-time curve of drug exposure (AUC), the product of time of exposure and concentration of drug, is a much better predictor of the duration of the PAE than either parameter alone. We also measured the PAE of imipenem against strains of gram-positive and gram-negative bacteria for which MICs varied widely.

Disc susceptibility testing for thermomphilic campylobacters.

The minimum inhibitory concentrations (MICs) and zone diameters around NCCLS strength discs of 100 clinical isolates of thermophilic Campylobacter species, including 79 strains of Campylobacter jejuni subsp. jejuni, 19 of C. coli and two of C.

Selection of optimum laboratory tests for the identification of Moraxella catarrhalis.

We evaluated a variety of conventional and rapid tests and examined the erythromycin susceptibility of a collection of Moraxella catarrhalis and commensal neisseria strains in order to determine the optimum method for routine identification. One hundred and fifty three strains were tested by Gram stain, catalase, oxidase, carbohydrate degradation by two methods and the presence of esterases using indoxyl acetate, 4-methylumbelliferyl butyrate (MUB). Tween 80 and tributyrin as substrates.

Risk factors for adverse cutaneous reactions associated with intravenous vancomycin.

We retrospectively studied adverse cutaneous reactions associated with intravenous vancomycin therapy over a 14-month period when two different brands of vancomycin were used. Of 224 adults, 12 (5.4%) had infusion-related reactions; ten of 174 patients who received more than one day of vancomycin (5.

Bactericidal activity and synergy studies of proton pump inhibitors and antibiotics against Helicobacter pylori in vitro.

The bactericidal activity of the proton pump inhibitors omeprazole and lansoprazole alone and in combination with a beta-lactam or macrolide antibiotic were investigated in vitro. Time-kill curves against Helicobacter pylori NCTC 11637 and a recent clinical isolate revealed significant concentration-dependent killing with all drugs other than amoxycillin. Combinations of proton pump inhibitor and erythromycin showed synergic activity.

Oxygen concentration influences proton pump inhibitor activity against Helicobacter pylori in vitro.

Omeprazole and lansoprazole are proton pump inhibitors that have shown activity against Helicobacter pylori and other Helicobacter species when tested by agar dilution. Lansoprazole was more active against H. pylori than was omeprazole, and the activity was independent of urease production.