ABSTRACT
Topical acyclovir favorably influences the healing of localized herpes zoster in immunocompromised patients. This therapy, or placebo, was applied to forty-three patients in a random access, double-blind trial, four times daily for 10 days, beginning within 72 hours after the onset of skin lesions. The mean time to pustulation is decreased from 12.4 to 6.7 days and the mean time to crusting is decreased from 16.0 to 11.4 days (p = 0.038 and 0.086, respectively) by topical treatment. The mean time to 50% healing is decreased from 24.5 to 15.2 days and the mean time to 100% healing is decreased from 34.9 to 25.8 days (p = 0.023 and 0.033, respectively). Favorable effects in treated patients are not associated with a more rapid decline in lesion virus titer, but do accrue without any toxicity.
Subject(s)
Acyclovir/therapeutic use , Herpes Zoster/drug therapy , Immunologic Deficiency Syndromes/complications , Acyclovir/administration & dosage , Administration, Topical , Adult , Clinical Trials as Topic , Double-Blind Method , Female , Herpes Zoster/etiology , Humans , Lymphoproliferative Disorders/complications , Male , Middle Aged , Random Allocation , Time FactorsABSTRACT
We assessed the efficacy of prophylactic antibiotics in children receiving intensive chemotherapy for acute lymphoblastic leukemia. The patients were randomized to receive either trimethoprim-sulfamethoxazole (TMP-SMX) or placebo in a double-blind trial. Thirty patients were evaluated in each group. Children receiving TMP-SMX had fewer episodes of bacteremia (0 vs. 5) and otitis media (3 vs. 18). The geometric mean of the neutrophil nadir was 172 in the TMP-SMX group and 287 in controls. However, no increased delay or dose reduction of chemotherapy was observed in the TMP-SMX treated patients. Five patients who received TMP-SMX developed Gram-negative rods resistant to TMP-SMX on surveillance stool cultures. We conclude that TMP-SMX prophylaxis decreased certain bacterial infections in children with acute lymphoblastic leukemia without causing clinically significant toxicity. The emergence of Gram-negative rods resistant to TMP-SMX in treated patients suggests that TMP-SMX prophylaxis should be restricted to patients who are at high risk for developing a bacterial infection or Pneumocystis carinii pneumonia.
Subject(s)
Bacterial Infections/prevention & control , Leukemia, Lymphoid/complications , Sulfamethoxazole/therapeutic use , Trimethoprim/therapeutic use , Administration, Oral , Adolescent , Bacterial Infections/etiology , Child , Child, Preschool , Clinical Trials as Topic , Double-Blind Method , Drug Combinations/administration & dosage , Drug Combinations/therapeutic use , Female , Humans , Infant , Male , Random Allocation , Sulfamethoxazole/administration & dosage , Suspensions , Trimethoprim/administration & dosage , Trimethoprim, Sulfamethoxazole Drug CombinationABSTRACT
Sixty-three immunocompromised patients with infections caused by herpes simplex virus were evaluated in a double-blind, placebo-controlled study of topical acyclovir therapy; 33 patients received acyclovir and 30 received the placebo. The two populations of patients were balanced in terms of age, race, sex, underlying disease, preceding chemotherapy, and site, size, and duration of lesions. Acyclovir recipients experienced an acceleration in the clearance of virus (P = .0006), the resolution of pain (P = .004), and the total healing of lesions (P = .038); median temporal differences between populations averaged six days for each of these three parameters. The surface area of herpetic lesions continued to enlarge in placebo recipients after entry into the trial; in contrast, lesion surface area decreased progressively during therapy in drug recipients. The speed of healing was influenced by lesion size. Patients with lesions of greater than or equal to 50 mm2 benefited most from therapy, particularly in terms of pain resolution and time to total healing (median differences between groups, eight days). Irrespective of underlying disease, sex, preceding chemotherapy, or age, acyclovir therapy was of clinical benefit. No adverse clinical or laboratory reactions were encountered.
Subject(s)
Acyclovir/therapeutic use , Herpes Simplex/drug therapy , Immune Tolerance , Acyclovir/administration & dosage , Acyclovir/adverse effects , Acyclovir/pharmacology , Administration, Topical , Adolescent , Adult , Aged , Child , Clinical Trials as Topic , Double-Blind Method , Female , Herpes Genitalis/drug therapy , Herpes Labialis/drug therapy , Humans , Male , Middle Aged , Recurrence , Simplexvirus/drug effects , Stomatitis, Herpetic/drug therapyABSTRACT
An acyclovir-resistant herpes simplex virus (HSV) has been isolated from an immunocompromised patient during treatment for severe orofacial HSV infections with acyclovir. The resistant virus is deficient in expression of the HSV thymidine kinase (TK). Emergence of acyclovir resistance during clinical use appears to parallel the in vitro observations of selection for TK-deficient, acyclovir-resistant viruses following serial passage in the presence of the drug. The clinical importance of drug-resistant HSV in unclear, and further investigations are required to determine whether it will be an impediment to successful therapy of HSV infections.
