Profiling penciclovir susceptibility and prevalence of resistance of herpes simplex virus isolates across eleven clinical trials.

Asusceptibility testing program was established to determine the prevalence of resistance to penciclovir among herpes simplex virus isolates collected from patients participating in 11 world-wide clinical trials involving penciclovir (topical or intravenous formulations) or famciclovir, the oral prodrug of penciclovir. These trials represented nine randomised double blind, placebo or aciclovir-controlled studies and two open-label studies. Groups surveyed included immunocompetent or immunocompromised patients receiving 2 to 12 months chronic suppressive therapy for genital herpes, immunocompetent patients with recurrent herpes labialis treated for four days, and immunocompromised patients with mucocutaneous herpes simplex virus (HSV).

Susceptibility of herpes simplex virus isolates to nucleoside analogues and the proportion of nucleoside-resistant variants after repeated topical application of penciclovir to recurrent herpes labialis.

Subjects received topical penciclovir for 4 days during successive episodes of recurrent herpes labialis. Isolation of herpes simplex virus (HSV) was attempted from lesions obtained before initiation of treatment and on each day of therapy. Isolates remained sensitive to penciclovir when tested by a plaque reduction assay, and there was no significant change in sensitivity during any treatment course or between successive treatments.

Using community pharmacies to conduct an HSV-1 prevalence study.

Purpose: To describe the effectiveness of community-based pharmacists in conducting a study to measure the baseline prevalence of Herpes simplex virus, type-1 susceptibility to two antiviral medications in subjects with recurrent Herpes labialis.

Method: A cross-sectional study conducted in 47 US community pharmacies. The pharmacist obtained a viral sample from the surface of the lesion, placed the virus-laden swab in a vial of holding medium, and stored it in a refrigerator until shipment to a central laboratory.

Surveillance for antiviral-agent-resistant herpes simplex virus in the general population with recurrent herpes labialis.

In a general population survey in the United States, the prevalence of antiviral-agent-resistant herpes simplex virus was very low among more than 1,000 isolates from individuals with an episode of recurrent herpes labialis not treated with topical antiviral agents. Two isolates had borderline resistance to acyclovir (0.2%), and all were susceptible to penciclovir.

Postherpetic neuralgia: impact of famciclovir, age, rash severity, and acute pain in herpes zoster patients.

New and previously reported analyses of the data from a placebo-controlled trial of famciclovir are reviewed in light of recently proposed recommendations for the analysis of pain in herpes zoster trials. The analyses examined the effect of famciclovir treatment on the duration of postherpetic neuralgia (PHN), which was defined as pain persisting after rash healing, pain persisting > 30 days after study enrollment, or pain persisting > 3 months after study enrollment; the baseline characteristics of patients in the famciclovir and placebo groups who developed PHN; the impact of famciclovir treatment on the duration of PHN, while controlling for significant covariates; and the prevalence of PHN at monthly intervals from 30 to 180 days after enrollment. The results of these analyses indicated that greater age, rash severity, and acute pain severity are risk factors for prolonged PHN.

Inaccurate haemoglobin estimation in Waldenström's macroglobulinaemia: unusual reaction with monomeric IgM paraprotein.

Automated blood counts from a patient with Waldenström's macroglobulinaemia repeatedly failed critical limit standards set for mean cell haemoglobin concentration and mean cell haemoglobin. Haemoglobin estimation was higher than that suggested by clinical examination, symptoms, and the spun haematocrit. This was found to be due to an interaction between the Coulter lysing agent and monomeric IgM paraprotein in the patient's plasma, creating a precipitate which was optically dense at 525 nm.

Acquired factor XI inhibitor in chronic lymphocytic leukaemia.

A 71 year old man with chronic lymphocytic leukaemia (CLL) experienced excessive bleeding following transurethral resection of the prostate. Investigations showed a prolonged kaolin cephalin clotting time (KCCT) with low concentrations of factor XI. The prolonged KCCT was largely corrected by mixing with normal plasma but this correction was lost on incubation, confirming the presence of an inhibitor.

Influence of clavulanic acid on the activity of amoxicillin against an experimental Streptococcus pneumoniae-Staphylococcus aureus mixed respiratory infection.

An experimental respiratory infection caused by Streptococcus pneumoniae was established in weanling rats by intrabronchial instillation. Treatment of this infection with amoxicillin rapidly eliminated the pneumococci from the lung tissue. A beta-lactamase-producing strain of Staphylococcus aureus, when inoculated in a similar manner, did not persist adequately in the lungs long enough to permit a reasonable assessment of the therapy, but staphylococcal survival was extended in the lungs of rats infected 24 h previously with S.

Lack of significant effect of therapeutic propranolol on measurable platelet function in healthy subjects.

Propranolol, a non-selective beta blocker, was administered orally in therapeutic doses. The effects of a single dose (160 mg) and one week's treatment (80 mg twice a day) on platelet function were compared in healthy young subjects. There were no significant changes in circulating platelet aggregates, template bleeding time, platelet factor 3 availability and thromboxane beta 2 (TX beta 2) generation.

Response of Streptococcus pyogenes to therapy with amoxicillin or amoxicillin-clavulanic acid in a mouse model of mixed infection caused by Staphylococcus aureus and Streptococcus pyogenes.

The response of Streptococcus pyogenes to amoxicillin or amoxicillin-clavulanic acid (Augmentin; Beecham Group) therapy of a mixed streptococcal-staphylococcal infection was studied in a surgical wound in mice. A superficial wound was produced on the backs of anesthetized mice, and a suture infected with S. pyogenes, Staphylococcus aureus, or a mixed inoculum of both organisms was inserted.

Bactericidal effects of ticarcillin-clavulanic acid against beta-lactamase-producing bacteria in vivo.

The comparative efficacies of ticarcillin and ticarcillin plus clavulanic acid have been determined in the mouse against experimental infections caused by ticarcillin-resistant bacteria. The infections studied comprised an intraperitoneal infection, local tissue infections, pyelonephritis, and pneumonia. Both ticarcillin and clavulanic acid penetrated readily to the sites of infection studied and at the doses employed were present at concentrations of the same order as those obtained in humans after the administration of ticarcillin-clavulanic acid formulations (Timentin; Beecham).

Antibacterial effects of ticarcillin/clavulanic acid in animal models of infection.

The therapeutic effects produced by ticarcillin plus clavulanic acid were compared with those of ticarcillin and clavulanic acid separately against infections in the mouse caused by beta-lactamase-producing bacteria. The infections studied included a pneumonia model, a local tissue infection and pyelonephritis. The distribution of ticarcillin and clavulanic acid in infected animals was evaluated by measurement of the concentrations of the substances present at sites of infection.

Antibacterial activity of ticarcillin in the presence of clavulanate potassium.

The antibacterial effects produced by ticarcillin disodium plus clavulanate potassium, a combination of the broad-spectrum penicillin ticarcillin, and the beta-lactamase inhibitor clavulanic acid as the potassium salt, have been measured in vitro and in experimental infection studies. The presence of clavulanic acid resulted in a significant enhancement of the activity of ticarcillin against a wide range of beta-lactamase-producing bacteria. These included ticarcillin-resistant strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P.

Efficacy of topical mupirocin against an experimental Staphylococcus aureus surgical wound infection.

The efficacy of topically-applied mupirocin was evaluated against an experimental surgical staphylococcal wound infection in the guinea-pig. A suture impregnated with Staphylococcus aureus was inserted into a superficial wound, and topical therapy with mupirocin ointment was started 24 h after infection. In non-treated wounds, the bacterial counts increased to greater than 10(6) organisms/wound in the majority of animals at 24 h, remaining at this level for up to seven days.

Studies with temocillin in a hamster model of antibiotic-associated colitis.

Hamsters given the new penicillin temocillin, either orally or by injection, did not develop antibiotic-associated colitis, whereas animals given the control antibiotics cefoxitin or clindamycin developed the disease, which is characterized by marked hemorrhagic cecitis and high cecal levels of Clostridium difficile cytotoxin.

Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use.

Mupirocin (pseudomonic acid A), an antibiotic produced by Pseudomonas fluorescens, showed a high level of activity against staphylococci and streptococci and against certain gram-negative bacteria, including Haemophilus influenzae and Neisseria gonorrhoeae, but was much less active against most gram-negative bacilli an anaerobes. Nearly all clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis, including multiply resistant strains, were susceptible (mupirocin MIC, less than or equal to 0.5 microgram/ml).

Studies with temocillin in the hamster model of antibiotic-associated colitis.

The studies reported here were designed to ascertain whether or not the new beta-lactam antibiotic, temocillin, would produce antibiotic-associated colitis in the hamster. The experiments were controlled with clindamycin and cefoxitin, which are known to induce antibiotic-associated colitis experimentally and clinically. All three antibiotics were administered to groups of animals both parenterally and orally.

Comparative biological properties of some synthetic olivanic acid analogues.

A series of olivanic acid/thienamycin analogues have been prepared by total synthesis. Particular attention was given to the effect of the side-chain substituents on the chemical, beta-lactamase and metabolic stability of the final products. All of the compounds possessed a broad and high level of in vitro antibacterial activity against Gram-positive and Gram-negative organisms including beta-lactamase-producing strains.

Properties of MM 13902 and other carbapenem antibiotics in vitro and in vivo.

The carbapenem antibiotics, which include the olivanic acids and the thienamycins, have a broad-spectrum of antibacterial activity but only thienamycin itself shows appreciable activity against Pseudomonas aeruginosa. The zwitterionic nature of thienamycin was reproduced in the olivanic acid series by preparing the deacetyl derivatives of MM 17880 and MM 22380--compounds NA 26975 and NA 26978. The latter derivative showed antipseudomonas activity and had an antibacterial spectrum similar to thienamycin itself.

Distribution of amoxicillin and clavulanic acid in infected animals and efficacy against experimental infections.

The therapeutic effects produced by formulations of amoxicillin plus clavulanic acid (BRL 25 000A and BRL 25 000G) were compared with those of amoxicillin and clavulanic acid separately against a variety of infections produced by amoxicillin-susceptible and beta-lactamase-producing (amoxicillin-resistant) bacteria. The infection models studied included intraperitoneal infections, a mouse pneumonia, experimental pyelonephritis, and local lesions caused by Staphylococcus aureus and Bacteroides fragilis. The distribution of amoxicillin and clavulanic acid in infected animals after the administration of amoxicillin-clavulanic acid was evaluated by measurement of the concentrations of the substances present in specimens collected at the sites of infection.

Comparative antibacterial properties in vitro of seven olivanic acid derivatives: MM 4550, MM 13902, MM 17880, MM 22380, MM 22381, MM 22382 and MM 22383.

Streptomyces olivaceus ATCC 31365 produces a family of novel beta-lactam antibiotics collectively referred to as the olivanic acids. Seven such compounds, MM 4550, MM 13902, MM 17880, MM 22380, MM 22381, MM 22382 and MM 22383 have been identified which have the same carbapenem nucleus but with different side chains attached to the nucleus. The compounds with an (8S) hydroxyethyl substituent and cis-orientated beta-lactam protons, MM 22380 and MM 22382, and their sulphate esters, MM 17880 and MM 123902, are potent antibiotic with MIC values against Gram-positive and Gram-negative bacteria in the range 0.