Penciclovir susceptibilities of herpes simplex virus isolates from patients using penciclovir cream for treatment of recurrent herpes labialis.
The antiherpesvirus agent penciclovir (PCV) shares an identical activation pathway and a similar mode of action with acyclovir (ACV). However, since PCV represents a relatively recent treatment option, the clinical resistance profile to PCV is less well known. A susceptibility program was established to assess the resistance profile for serial herpes simplex virus isolates from immunocompetent patients with recurrent herpes labialis obtained throughout a 4-day period of treatment with topical PCV (1% cream) or a placebo. Two isolates (2 of 1,035 [0.19%]), representing 0.34% of the patients (2 of 585), were confirmed to be PCV-resistant (Pcv(r)) herpes simplex virus type 1 by a plaque reduction assay in MRC-5 cells. These two viruses were highly resistant to PCV (50% inhibitory concentrations [IC(50)s], >55 micro g/ml) and were isolated less than 17 h after the start of patient-initiated treatment. However, subsequent isolates on days 2 and 3 from these patients were completely susceptible to PCV (IC(50)s, <2.0 micro g/ml). Thus, it is not clear whether the resistance to PCV for these two early-treatment isolates was directly associated with the 17 h of PCV treatment; several possible explanations are discussed. In an analysis of the distribution of IC(50) differences between the first and last isolates, there were three patients with minor IC(50) increases in the PCV-treated population and one in the placebo-treated group, although statistically, only the latter was an outlier. No patients were found to have Pcv(r) virus at the end of acute treatment, regardless of treatment group. Overall, the prevalence of Pcv(r) was found to be similar to the 0.3% Acv(r) reported for immunocompetent, untreated populations.
Department of Host Defense, The Antimicrobial and Host Defense Center of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, Collegeville, Pennsylvania 19426-0989, USA. robert_t_sarisky@gsk.com
Robert T
RT
Sarisky
Teresa
T
Bacon
Ron
R
Boon
Leslie
L
Locke
Tammy T
TT
Nguyen
Jeffry
J
Leary
Klaus
K
Esser
Robin
R
Saltzman
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001345:Autoradiography; D024882:Drug Resistance, Viral; D016368:Frameshift Mutation / Q000235:genetics; D006147:Guanine; D006560:Herpes Labialis / Q000188:drug therapy* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012008:Recurrence; D010948:Viral Plaque Assay
D000998:Antiviral Agents; C053539:penciclovir; D006147:Guanine; D011505:Protein-Tyrosine Kinases; D000212:Acyclovir