Virus resistance in clinical practice

Dekker, Cornelia D.; Ellis, M N; McLaren, Colin; Hunter, G.A.; Rogers, James V.; Barry, David W.

doi:10.1093/jac/12.suppl_b.137

Cited by 62 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sensitive HSV isolates had ID50 of <8 pmol/liter (6) useful in treating infections due to acyclovir-resistant HSV, such as those described in this report and by others (2,10). Additionally, continuous infusion may be useful in therapy of B-cell lymphoproliferation induced by EBV.…”

mentioning

confidence: 60%

Continuous infusion of high-dose acyclovir for serious herpesvirus infections

Fletcher

Englund

Bean

et al. 1989

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Thirteen patients with herpesvirus infections who were unresponsive to at least 72 h of intermittent acyclovir administration received high-dose continuous infusion. Steady-state concentrations were maintained at between 20 and 98 ,umol/liter. Of 12 patients who had continuous infusion for >5 days, 7 (58%) resolved their infections, as determined by clinical and virologic parameters, suggesting that continuous infusion may succeed in some patients who do not respond to conventional therapy.Acyclovir is a purine nucleoside with in vitro activity against herpes simplex virus (HSV), varicella-zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) (1). The drug has been shown to be of clinical benefit when administered topically, orally, or parenterally for the prophylaxis and treatment of certain herpesvirus infections (1). While acyclovir is conventionally given by intermittent oral or intravenous routes, the method of administration that best inhibits viral replication is not known. This report describes the use of high-dose acyclovir given by continuous intravenous infusion to 13 patients with serious herpesvirus infections.Patients hospitalized at the University of Minnesota Hospital were eligible for this study if they (i) had serious, systemic, life-threatening herpesvirus infections; (ii) had received at least 72 h of intermittent oral or intravenous acyclovir; and (iii) were judged by the attending physicians to have had poor responses to conventional, intermittent acyclovir administration. Clinical indicators of poor response included continued fever and weakness in CMVinfected individuals, progression of mucocutaneous lesions in HSV-infected individuals, and continued fever or lymphadenopathy in EBV-infected individuals.The acyclovir dosing regimen for continuous infusion was designed by using a two-compartment pharmacokinetic model (5), with acyclovir elimination defined as a function of creatinine clearance (CLCR). Nominal values of the pharmacokinetic parameters used for simulation of concentration in plasma and dosage regimen design were as follows: volume of distribution of the central compartment, 0.32 liter/kg of body weight, and intercompartmental rate constants of 1.3 h-1 (k12) and 0.8 h-1 (k21 (Fig. 1). To optimize therapy, the administration rate was subsequently increased in patients 2, 3, 4, 10, and 12. Acyclovir CL (Fig. 2)

show abstract

mentioning

confidence: 60%

Continuous infusion of high-dose acyclovir for serious herpesvirus infections

Fletcher

Englund

Bean

et al. 1989

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…A number of previous studies demonstrating in vitro complementation/recombination of either TK+/TKvirus mixtures or between avirulent viruses have been published (Tenser et al, 1981 ;Field & Lay, 1984;Javier et al, 1986;Tenser & Edris, 1987;Sedarati et al, 1988) however, the results presented here are the first to follow complementation of a deletion mutant within the CNS and PNS during both acute and latent infection by Southern blot hybridization. It is of interest that studies on the sensitivity of clinical isolates to ACV from early clinical trials with this compound found a number of the isolates to contain mixtures of resistant and sensitive viruses (Dekker et al, 1983) and that similar observations have been made in experimental infections of mice (Field & Lay, 1984). These results suggest that in vivo complementation between TK + and TKviruses may be a mechanism by which TK-drug-resistant virus could be maintained in the population.…”

Section: Discussionmentioning

confidence: 81%

The Role of Herpes Simplex Virus Type 1 Thymidine Kinase in Pathogenesis

Efstathiou

Kemp

Darby

et al. 1989

Journal of General Virology

218

162

View full text Add to dashboard Cite

SUMMARYA genetically engineered herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) deletion mutant has been constructed and used to investigate the role of this gene in pathogenesis. Inoculation of mice with the HSV TK deletion mutant resulted in the establishment of latent ganglionic infection as demonstrated by superinfection of explanted ganglia with wild-type (wt) virus bat not by routine explant culture suggesting that the virus-encoded TK is not essential for the establishment of latent infection but may be necessary for either reactivation or virus replication following reactivation. In addition, Southern blot hybridization has been used to demonstrate in vivo complementation of this mutant by wt virus in both peripheral and central nervous system tissues of mice during acute infection and to show that such complementation can result in the establishment and reactivation of latent TK-infection.

show abstract

“…Although animal studies have suggested that TKdeficient mutants are less virulent and less able to establish neural latency (18,51), TK-deficient strains have been isolated from ACV-treated IC patients with active HSV infection (8,51,60). ACV-resistant strains of HSV have also been recovered from patients who have never been treated with ACV (15,40). The clinical significance of ACV resistance is further confounded by the observation that TKdeficient mutants have been isolated from lesions from IC patients who have responded to treatment with AI2V (8,14,62); no clear relationship has been established between response to prophylactic therapy and in vitro susceptibility testing of specific clinical isolates.…”

Section: Emergence Of Resistancementioning

confidence: 99%

Acyclovir prophylaxis for herpes simplex virus infection

Gold¹,

Corey²

1987

Antimicrob Agents Chemother

100

View full text Add to dashboard Cite

ACV is an effective agent for the treatment and prophylaxis of HSV infections in both IC and immunologically normal individuals. The drug is well tolerated in both populations and is not significantly associated with clinical or laboratory toxicities. Because of the great potential benefit and low risk, organ transplant recipients and patients with hematologic malignancies undergoing induction chemotherapy should be screened routinely for HSV antibodies; seropositive individuals should receive prophylactic ACV during the period of most profound immunosuppression. Immunologically normal individuals with frequently recurring genital HSV or serious complications associated with outbreaks are candidates for long-term suppression with ACV.

show abstract

Virus resistance in clinical practice

Cited by 62 publications

References 0 publications

Continuous infusion of high-dose acyclovir for serious herpesvirus infections

Continuous infusion of high-dose acyclovir for serious herpesvirus infections

The Role of Herpes Simplex Virus Type 1 Thymidine Kinase in Pathogenesis

Acyclovir prophylaxis for herpes simplex virus infection

Contact Info

Product

Resources

About