Summaries from the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy: Part II

conference coverage

Note: The following summaries represent a selection of papers from those presented at the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held September 24-27, 1998, in San Diego, CA. It is important to recognize that many of these summaries are extracted only from the published abstracts, and it is possible that some of the material may have differed at the time of presentation. —Stan Deresinski, MD, FACP

Viral Pathogens

Influenza

Two agents are currently available for the prophylaxis and treatment of influenza A virus infections. Consistent with previous reports, amantadine use was associated with a significantly greater incidence of CNS adverse effects than was the use of rimantidine in elderly nursing home residents. (Abstract H-73.)

Several new agents, active against both influenza A and B virus, are in clinical trials. Zanamivir, a selective inhibitor of the neuraminidase of both types of influenza virus, was evaluated in a placebo-controlled, randomized trial involving more than 1200 patients with acute influenza. The median time to symptom improvement was one day shorter in those receiving active drug (6 days vs 7 days in placebo recipients; P = 0.012) and was 2.7 days shorter in a subset of "at risk" patients (5.3 vs 8 days; P = 0.016). Virological studies in a subset of 40 patients demonstrated more rapid clearance of viral shedding in zanamivir recipients; emergence of resistance during therapy was not detected. (Abstract H-67.) Similar results were obtained in a Southern Hemisphere study. (Abstract H-56.)

GS4104 (Ro 64-0796) is a prodrug of GS4071, another influenza A and B virus neuraminidase inhibitor. In a randomized placebo-controlled study of 629 U.S. patients with acute febrile respiratory illness, 374 (60%) of whom had influenza virus infection, GS4104 shortened the duration of symptoms due to influenza virus by a median of 1.4 days (2.9 vs 4.3 days; P = 0.0001). The severity of illness and incidence of secondary complications, predominantly sinusitis and bronchitis, were also reduced. (Friday, Abstract LB-4.) A second study performed in Canada, Europe, and China found similar results. (Friday, Abstract LB-5.)

Both zanamivir and GS4104 were reported to be effective in the prophylaxis of influenza virus infection. In a study of 1559 non-immunized adults, zanamivir administration was compared to placebo. Each was administered for six weeks during a period of local influenza activity. GS4104 administration was associated with a 74% protection rate against illness due to influenza. (Friday, Abstract LB-6.) Daily inhalation of zanamivir for four weeks was associated with an 84% reduction of febrile influenza virus infection and a 67% reduction in laboratory-confirmed influenza infection, when compared to placebo. (Friday, Abstract LB-7.)

The effectiveness of influenza vaccination of children attending day care centers was evaluated in a study in which hepatitis A vaccine was used as a placebo. Influenza vaccination was associated with a significant reduction in respiratory illness in household members, with the greatest effect on siblings ages 5-17 years, among whom there was a 55% reduction in respiratory illnesses and a 78% reduction in febrile respiratory illnesses. There was also a reduction in the number of school days missed, number of physician visits, and antibiotic prescriptions. (Friday, Abstract LB-8.)

Respiratory Syncytial Virus

In a placebo-controlled, randomized blinded study, no benefit from ribavirin administration to previously healthy infants undergoing mechanical ventilation because of RSV bronchiolitis could be demonstrated. (Abstract H-60.)

There is increasing recognition of the role of RSV as an important cause of respiratory infections in adults. A prospective observation of 134 adults with severe COPD or CHF over two winter seasons found that three of 12 hospitalizations were associated with RSV infection. (Abstract H-70.)

Herpes Viruses

HSV. Famciclovir (500 mg tid for 7 days) was equivalent, in a blinded, randomized trial, to acyclovir (800 mg 5 times daily for 7 days) in the treatment of a total of 454 patients with ophthalmic branch herpes zoster. (Friday, Abstract LB-3.)

Our understanding of clinical aspects of herpes simplex encephalitis is becoming increasingly complex, with the recognition of unusual presentations as well as the danger of relapse. Five (13.5%) of 37 patients with prior herpes simplex encephalitis had a total of nine apparent relapses during a median period follow-up of 8.7 years. However, HSV DNA could not be demonstrated in any of the 19 CSF samples obtained during the apparent relapse. (Abstract H-13.)

Recurrent neurological disease due to HSV takes a variety of forms. Retrospective analysis of 28 consecutive patients with meningomyelitis and/or radiculitis due to HSV-2 followed for at least one year found that 18 (64%) had neurological recurrence. (Abstract H-15.)

HSV is an important cause of Bell’s palsy. Approximately one-half of 225 patients with Bell’s palsy had neurological symptoms not related to the facial nerve, including blurred vision, memory loss, limb paresthesias, incoordination, and ataxia, indicative of diffuse HSV-1 neurological reactivation. The investigators conclude that Bell’s palsy should be considered an "HSV reactivation polyganglionitis." (Abstract H-17.)

The occurrence of acyclovir-associated neurotoxicity in patients with end stage renal disease correlated with the accumulation in serum of 9-carboxymethoxymethylguanine (CMMG), the concentration of which is reduced 50% by a single hemodialysis session. (Abstract A-83.)

Varicella-Zoster

The evidence of the value and efficacy of varicella vaccination in susceptible individuals continues to grow. The cumulative antibody persistence rate four years after a single dose of the Merck varicella vaccine is 99.8%, and five-year follow-up indicates it provides 89.2% protection following household exposure. When varicella did occur in vaccine recipients, it was mild, with patients developing only 16-34 lesions. (Abstract H-19.)

Life-threatening streptococcal infections have been reported as a complication of varicella infection in children. In a population-based surveillance study, the incidence of invasive infection due to S. pyogenes in the month following chickenpox was 5.2/100,000 compared to 0.09/100,000 in those without chickenpox. Despite the fact that it is an uncommon complication of chickenpox, it is estimated that 15% of all invasive S. pyogenes infections in children could be prevented by routine VZV vaccination. (Abstract L-95.)

CMV

Intraoperative hypothermia is an independent risk factor for CMV infection in liver transplant recipients. (Abstract H-102.)

Erythroviruses

An erythrovirus (V9) with more than 14% genomic divergence from parvovirus B19 was detected in the serum of a child with aplastic anemia who had negative PCR and IgM serology for B19. Using a broadly reactive PCR for human erythroviruses, a positive result was obtained in the serum of 18 of 43 patients with either sickle cell anemia and aplastic crisis, HIV infection with chronic anemia, or acute anemia with weak B19 PCR positivity. Five of the 18 positives were due to the presence of V9, while the remainder were due to B19. The pathogenicity and taxonomic status of V9 remain to be determined. (Friday, Abstract LB-1.)

Transfusion-Transmitted Virus’

Transfusion-transmitted virus (TTV) is a recently identified novel DNA virus that appears to be parenterally transmissible, but whose role as an agent of human disease remains undetermined (Lancet 1998;352:191, 195; Infect Dis Alert 1998;17:185). TTV DNA was detected in the serum of 22 (95.6%) of 23 infants born to TTV-positive mothers; in contrast, only one (2.3%) of 43 infants born to HCV-infected mothers became HCV positive. TTV DNA was detected in breast milk of 17 (73.9%) of the TTV infected mothers. However, all 17 TTV-positive infants tested in the first week of life were already infected, indicating that the high rate of vertical transmission was the result of infection during pregnancy. None of the 22 TTV infected children had biochemical evidence of hepatitis. (Friday, Abstract LB-2.)

Hepatitis B

Hair loss after hepatitis B vaccination has been reported. However, a case-control study failed to find evidence of a statistically significant increased risk of alopecia after HBV vaccination in children. (Abstract H-131.)

Rubeola

Measles inclusion body encephalitis due to vaccine strain virus occurred in a previously healthy 21-month-old infant 8.5 months after vaccination. (Abstract H-134.)

Tick-borne Infections

Serological screening of healthy blood donors in Westchester County, New York, found that 15.7% were seropositive for antibodies to the agent of human granulocyte ehrlichiosis and 29.7% had antibody to Borrelia burgdorferi. (Abstract D-81.)

Plasma is superior to serum as a culture source for recovery of B. burgdorferi in patients with early stage Lyme disease. (Abstract D-3.)