Updates
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
VZIG — No Longer Available
VariZIG for Prophylaxis after Exposure to Varicella. Med Lett Drugs Ther. 2006;48:69-70.
The only manufacturer of VZIG in the United States recently stopped its production. An alternate product, VariZIG, which is manufactured by a Canadian company and has not been approved for use in the United States by the FDA, can be obtained in the United States, but only through expanded access as an investigational new drug. VariZIG is prepared from pooled human plasma, similar to VZIG, and has been treated with filtration and inactivation methods. As such, there remains a small risk of transmission of blood born pathogens.
Varicella immune globulin is indicated for those exposed patients who are at high risk for complications from varicella infection, for whom varicella vaccination is contraindicated. In the United States, these include: non-immune pregnant women; non-immune immunocompromised persons; neonates born to mothers with varicella infection between 5 days before and 2 days after delivery; premature infants > 28 weeks gestation born to non-immune mothers; and premature infants < 28 weeks gestation or who weigh < 1000 grams who are exposed regardless of the mothers immune status.
The expanded access protocol has central IRB approval, but local institutional approval may be needed. In order to receive VariZIG in the United States, contact FFF Enterprise, which is the only authorized distributor (24 hour telephone number (800) 843-7477). The company will review eligibility before shipping the drug within 24 hrs. Signed informed consent is required, and a brief case record form with 4 visits is required.
Prosthetic Joint Infection
Marculescu CE, et al. Outcome of Prosthetic Joint Infections Treated with Debridement and Retention of Components. Clin Infect Dis. 2006; 42:471-478.
Debridement and retention of components is commonly employed for the treatment of prosthetic joint infection (PJI), especially for those who are poor candidates for a second (or third) joint replacement. In this retrospective review, Marculescu and colleagues assessed all patients with a total hip or knee arthroplasty who developed PJI and underwent debridement and retention of components between 1995 and 1999 at the Mayo Clinic in Rochester, Minnesota. A total of 99 PJI occurred in 91 individuals, with a median age of 74. About one-third of the patients were febrile, 13% had evidence of radiographic lucency, and 6% were bacteremic. Patients underwent a median of one surgical debridement (range, 1-4) but just the first was considered for statistical purposes. Purulence was noted in 56% of the cases. The polyethylene parts were exchanged in addition to debridement in nearly half of the cases.
S. aureus and coagulase-negative staphylococci were the most common organisms identified in culture (32% and 23% of the cases, respectively), followed by Streptococcal spp (14%), gram negative organisms (6%), enterococci (3%), and anaerobic infection (1%). Eight (8%) of the cases were polymicrobial and 8% were culture negative.
Of the 99 episodes, 93 were treated with parenteral antibiotics for a median of 28 days (range, 1-90 days); 6 episodes were treated with oral antimicrobials, including oral fluconazole in one case. Following this, 89% of the episodes were treated with long-term chronic oral suppressive antimicrobial therapy for a median of 541 days (range, 5-2673 days); in 11 episodes, long term suppressive therapy (LTST) was not administered; 6 of these patients either rapidly failed parenteral therapy or died.
A total of 46 (52%) of 88 episodes treated with LTST ultimately recurred; 9 of whom had stopped their treatment. Only one of 10 persons who stopped their LTST therapy remained disease free. Of those who did not received LTST, treatment failure occurred in 7 of 11 (63%) of episodes. The other 4, 3 of whom were initially culture negative, remained disease free at follow-up.
The overall 2-year disease-free survival rate was 60% (95% confidence interval, 50%-71%). Risk factors for treatment failure included the presence of a sinus tract (hazard ratio 2.84) and duration of symptoms prior to surgery > 8 days (hazard ratio 1.77). The 2-year disease-free survival rate for patients with S. aureus infection was 22%, compared with 82% for PJI episodes due to coagulase-negative Staphylococci or Streptococcal spp. There was no association between the risk of treatment failure and a history of diabetes, rheumatoid arthritis, prosthesis age, or prosthesis loosing. Debridement and retention of prosthesis in patients with infected THA/TKR may be an attractive option, especially for those patients who are not good surgical candidates or for those with non-S. aureus infection. However, long-term suppressive antibacterial therapy (without an apparent end point) was necessary to prevent relapse most cases.
Public Health Cost of Imported Measles
Parker AA, et al. Implications of a 2005 Measles Outbreak in Indiana for Sustained Elimination of Measles in the United States. N Engl J Med. 2006;355:447-455. Erratum in: N Engl J Med. 2006;355:1184.
Parker and colleagues describe the public health effort required to contain the largest outbreak of measles occurring in the United States in the past 10 years. The outbreak, which occurred in Indiana in 2005, began when a 17-year-old girl who was incubating measles arrived from Romania. The following day she attended a church gathering with ~500 people. Within days, a 6-year-old girl attending the event was hospitalized. The outbreak quickly spread in this highly unvaccinated community — largely because of the presence of unvaccinated children of parents who were concerned about the safety of measles vaccination.
Over the next 6 weeks, 3 waves of measles infection occurred. Sixty-six persons were suspected to have measles; 34 persons were confirmed. Fifty individuals lacked immunity to measles (~10% of the gathering), and evidence of vaccine failures occurred in 2 infected individuals. Three patients required hospitalization, including a hospital phlebotomist who developed pneumonia requiring ventilatory support for 6 days.
Virus isolated from 4 of the patients was identical, and all were genotype D4, which is endemic to Eastern Europe, as well as the Middle East and India.
Parker et al estimate that containment of the outbreak involved 3 different public health departments, 29 public health employees, 3650 person hours, and 4800 telephone calls; an estimated cost of $168,000 (~$5000 per infected patient). A total of 465 doses of MMR and 210 doses of prophylactic immune globulin were administered.
Importation of measles infection remains the single most important source of measles in the United States. Individuals in their 30s and 40s may be more vulnerable than previously suspected, possibly due to waning immunity. No nation currently requires measles vaccination for entry, including the United States. While this report was in press, a second, smaller outbreak occurred in Boston in May, 2006, when a young female computer programmer was recruited from India to work at the John Hancock Tower (where ~2000 people work). A total of 14 cases of measles occurred, including 12 employees in the building and 2 other Boston residents. Health care facilities should be alert to the possibility of measles infection in any immigrant or traveler with a febrile exanthem, and promptly alert public health authorities.
HBV with de novo Adefovir Resistance
Schildgen O, et al. Variant of Hepatitis B Virus with Primary Resistance to Adefovir. N Engl J Med. 2006,354:1807-1812; Chang TT, Lai CL. N Engl J Med. 2006;355:322-323.
Newer data suggest that ~2% of naturally occurring HBV may exhibit de novo resistance to adefovir. The authors describe cases of a variant HBV with primary resistance to Adefovir that remained sensitive both in vivo and in vitro to tenofovir (Viread, Gilead Sciences). The 3 patients, 2 of whom were married, were initially treated, and failed lamivudine as part of a clinical trial involving ~80 persons. All 3 subsequently received adefovir without any virologic response, but later responded to tenofovir.
The 3 strains of HBV proved to have the same unique amino acid substitute in the reverse transcriptase domain (rtI233v). The mutation was independent of lamivudine resistance, and remained stable for up to 220 weeks, even in the absence of selective pressure from adefovir. All 3 strains were typed a genotype D, which has a worldwide distribution and is the most common HBV genotype. A GenBank search found only 3 of 500 previously sequenced strains containing this mutation (2 from southeast Asia, both genotype C, and one from a Gibbon).
The initial significance of this mutation was not clear. Strains containing the mutation exhibited reduced in vitro sensitivity to adefovir by a factor of about 6 to 10, compared with wild type virus. Site-directed mutagenesis, whereby the isoleucine group at position 233 was converted back to wild type virus containing valine, demonstrated adefovir-sensitive virus.
Separately, another clinical trial compared the effectiveness of entacavir and lamivudine in patients with HBV infection. Eight patients receiving entacavir were found to be infected with a rtI233V mutant strain. Seven of the 8 patients developed undetectable viral loads, and 6 of 6 with available histologic data had histologic improvement. Although these patients did not have pre-existing lamivudine resistant, entecavir may be a good therapeutic option for patients with this variant mutation. Although tenofovir is not approved for use in patients with HBV, HIV providers have been using it successfully as part of an antiretroviral regimen for HBV/HIV co-infected persons.
The only manufacturer of VZIG in the United States recently stopped its production. An alternate product, VariZIG, which is manufactured by a Canadian company and has not been approved for use in the United States by the FDA, can be obtained in the United States, but only through expanded access as an investigational new drug.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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