Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis: a double-blind, randomized controlled trial.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is a common cause of acute and recurrent aseptic meningitis. Our aim was to determine the impact of antiviral suppression on recurrence of meningitis and to delineate the full spectrum of neurological complications. METHODS: One hundred and one patients with acute primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled, multicenter trial. The primary outcome was time until recurrence of meningitis. The patients were followed up for 2 years. RESULTS: The first year, no significant difference was found between the valacyclovir and placebo groups. The second year, without study drugs, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients exposed to valacyclovir (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the patients experienced 1-4 meningitis episodes during the study period. A considerable morbidity rate, comprising symptoms from the central, peripheral, and autonomous nervous system, was found in both groups. CONCLUSIONS: Suppressive treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit recurrent meningitis and cannot be recommended for this purpose after HSV meningitis in general. Protection against mucocutaneous lesions was observed, but the dosage was probably inappropriate for the prevention of HSV activation in the central nervous system. The higher frequency of meningitis, after cessation of active drug, could be interpreted as a rebound phenomenon.

Erysipelas: clinical and bacteriologic spectrum and serological aspects.

The bacteriologic, serological, and clinical characteristics of 229 patients with erysipelas diagnosed during a 2-year period at a university hospital for infectious diseases in Sweden are presented. Beta-Hemolytic streptococci were detected in 34% of these patients. Group A was the dominant serogroup, but group G streptococci were found in about half as many cases. Bacteremia was present in 5%. A serological response with antistreptolysin O (ASO) and antideoxyribonuclease B (ADNase B) was seen primarily in patients harboring group A streptococci but also in those from whom no pathogen was isolated. ASO was also found in high titers in some patients with Group G streptococcal infection. The clinical course was usually benign, with few complications, but recurrences were common (occurring in 21% of the patients). No cases of streptococcal toxic shock were seen. Culture of skin biopsy specimens had low sensitivity; Beta-hemolytic were isolated from only two of 15 patients.

Streptococcal toxic shock syndrome in a postpartum woman. Case report and review of the literature.

A case of streptococcal toxic shock syndrome in a 29-year-old postpartum woman is described. The patient presented with hypotension, coagulation defects, adult respiratory distress syndrome and scarlet exanthema as a complication of hemolytic group A streptococcal endometritis. One hundred and twenty-two other cases of streptococcal toxic shock syndrome in the literature are reviewed and the criteria of the syndrome discussed. Streptococcal toxic shock syndrome seems to be increasing along with more frequent invasive streptococcal infections in several countries. It is therefore important to recognize and treat the infection as early as possible to minimize the risk of mortality.

Parvovirus B19 infection in HIV-1 infected patients with anemia.

Serum samples were analysed for IgM and IgG antibodies to parvovirus by ELISA and for parvovirus B19 DNA by polymerase chain reaction (PCR) in 69 HIV-1 infected Swedish patients with anemia and in 37 HIV-1 infected subjects without anemia. In 5/69 anemic patients, parvovirus B19 DNA was detected despite the lack of IgM antibody activity to the virus. The detection of parvovirus B19 DNA was significantly correlated to the degree of anemia in the anemic patients. In two patients who had a chronic anemia, a persistent parvovirus infection was detected by PCR, but not by serology, for 1 and 1.5 years, respectively. The results suggest that persistent parvovirus infection is a rare cause of anemia, but important to identify, since the infection is potentially treatable with intravenous immunoglobulin.

Antibiotic prophylaxis in recurrent erysipelas.

Recurrences of erysipelas are especially prevalent in patients suffering from local impairment of circulation and intervention might thus be of benefit. Therefore a prospective, randomized, open study was undertaken to evaluate whether daily antibiotic prophylaxis would reduce the risk of recurrence. Patients with venous insufficiency or lymphatic congestion who had suffered two or more episodes of erysipelas during the previous 3 years and were admitted to the Infectious Disease Department at Roslagstull Hospital, Stockholm, Sweden, between November 1988 and November 1991 were included. Fourty patients, 20 on prophylaxis and 20 controls were followed according to a life table analysis during a median time of 15 months. Phenoxymethylpenicillin was prescribed as daily prophylaxis (while erythromycin was given to patients allergic to penicillin). Recurrences of erysipelas appeared to be reduced by daily antibiotic prophylaxis but the effect was not dramatic (p = 0.06). Only in patients with a high recurrence rate continuous antibiotic prophylaxis against erysipelas is indicated.

Efficacy of triple drug regimen of amikacin, ethambutol and rifabutin in AIDS patients with symptomatic Mycobacterium avium complex infection.

Treatment with ethambutol 15 mg/kg, rifabutin 6 mg/kg and amikacin 15 mg/kg (IV for 2-4 weeks) in 31 HIV infected patients with severe immunodeficiency and infection caused by Mycobacterium avium complex (MAC) was evaluated in a retrospective study. The patients had one or more of the following clinical features: fever 31, weight loss 13, cough 10, pleurisy I, pericarditis 2, diarrhoea 12, peritonitis I. MAC was cultured from blood in 29, bone marrow in six, sputum in nine, faeces in 15, bowel biopsy in six and liver biopsy in four patients. Twenty-two of the 31 patients showed treatment response after a median time of 14 days, and five had a relapse successfully treated with another course of amikacin. Median survival time was 8 months.

Skin concentrations of phenoxymethylpenicillin in patients with erysipelas.

In 45 patients hospitalized with febrile erysipelas that had been treated with oral penicillin, punch biopsies of infected skin were performed and analysed for phenoxymethylpenicillin (pcV) concentrations. The curves for the concurrent serum and tissue levels followed the same course, indicating a rapid diffusion of pcV from serum into tissue. Penicillin concentrations in infected skin exceeded the minimal inhibitory concentrations (MIC) of the streptococci isolated for the first 4 h after tablet ingestion. Venous insufficiency was highly prevalent and pcV concentrations in affected patients were slightly but not significantly higher. A theoretical basis for the successful treatment of erysipelas with oral penicillin is therefore at hand.

Could Swedish 'yellow cards' be substituted by E-coded summaries?

Case summaries of 2490 patients treated at the Department of Infectious Diseases, Danderyd Hospital, in 1986 were reviewed for discharge diagnoses where the International Classification of Disease (ICD) code indicated an adverse drug reaction (ADR) [E 939,9 in ICD 8]. Of 48 patients whose case summaries indicated an ADR, only 10 (21%) had been reported on 'yellow cards' to the Swedish Adverse Drug Reactions Advisory Committee. The Committee had also received from the same department 3 reports where the case summary lacked an ADR code. The information on drug treatment with respect to dosage, duration and treatment with concomitant drugs was not complete in the case summaries but sufficient for a preliminary evaluation of the suspected reactions in all but 4 of the cases. On the basis of these findings the authors do not reach an outright conclusion in favour of replacing the 'yellow card' system but the possible benefits of a system in which 'yellow cards' are supplemented by automatic referral of all case summaries containing an ICD code indicating an adverse drug reaction was judged sufficient to recommend and initiate a large field study.

Septic osteomyelitis and polyarthritis with ureaplasma in hypogammaglobulinemia.

We describe a hypogammaglobulinemic woman with a one-year history of destructive septic osteomyelitis and polyarthritis with positive cultures for Ureaplasma urealyticum from joint exudate and blood. The clinical course was complicated by subcutaneous abscesses from which both U. urealyticum and Mycoplasma hominis were grown. Multiple routine cultures had been negative, except for sporadic findings of Staphylococcus epidermidis before specific cultures for mycoplasmas were performed. Therapy with beta-lactam antibiotics, clindamycin, rifampicin, fusidic acid and aminoglycosides had been given without obvious clinical effect. Intravenous doxycycline treatment instituted after microbiological diagnosis had a dramatic effect on the clinical course. The clinical suspicion of mycoplasma and ureaplasma as etiologic agents of orthopaedic infections in hypogammaglobulinemic patients is mandatory in order to perform appropriate cultures.

Recurrent erysipelas: predisposing factors and costs of prophylaxis.

After an average follow-up time of three years, recurrent erysipelas was observed in 29% of 143 patients admitted primarily with erysipelas. Nineteen patients (13%) had two or more recurrences during this period. The predisposing factor with the highest recurrence rate was venous insufficiency. Regular prophylaxis with phenoxymethylpenicillin (or erythromycin in penicillin allergics) after the second recurrence may be cost-effective. This antibiotic prophylaxis is only recommended in patients with predisposing factors who have suffered severe attacks.

Reduction of paracetamol and aspirin metabolism during viral hepatitis.

The single-dose pharmacokinetics of two analgesic drugs, paracetamol (acetaminophen) and aspirin, were studied in healthy volunteers and in patients with viral hepatitis during the acute and the convalescent phase. Impaired elimination of paracetamol and aspirin was found in hepatitis patients, while plasma peak concentrations were unaffected. Recovered patients were not different from healthy controls in the rate of drug elimination. The data suggest normal single dosage for these drugs in acute viral hepatitis, and dosage modification only in severe cases.

Epidemiological, bacteriological and complicating features of erysipelas.

233 patients with erysipelas, admitted to the Department of Infectious Diseases, Danderyd Hospital, during a 2-year period were analysed for epidemiological, bacteriological and complicating features. Erysipelas was defined clinically as a febrile skin infection with a sudden onset of a red indurated expanding plaque with a distinct border. Common predisposing factors were alcohol abuse, diabetes mellitus and venous insufficiency, and complications were more common among such patients. No seasonal variation was found. 5% of patients with blood culture had streptococcemia (7/149). Erysipelas emerging from an infected ulcer was seen in 52% (122/233) and in 46% of these streptococci were isolated (57/122), 67% of which were of type A (38/57). Staphylococcus aureus was isolated from 59% of ulcerative cases (72/122) and in 3 of them staphylococci were found in the blood.

The course, costs and complications of oral versus intravenous penicillin therapy of erysipelas.

Oral versus intravenous antibiotic therapy of severe erysipelas was compared in a controlled trial of 60 patients. No clinical benefit of intravenous therapy was found, as evaluated by fever duration, hospital stay and sick leave. Untoward reactions were comparable between the groups. No difference in recurrence was found. The difference in administration time and drug cost was considerable. It is therefore suggested that erysipelas without complications should be treated orally.

Efficacy of reporting systems of adverse reactions to drugs and care.

Only 13% of adverse drug reactions that should have been reported to the Committee on Side Effects in Sweden according to the criteria published by the National Board of Health and Welfare, were actually reported by the responsible doctors. This was found in a prospective study of all adverse reactions established in 1 271 patients at a department of infectious diseases. It was also found in retrospect that only half of the patients affected by complications making them eligible for compensation from the Patients' Insurance Office existing in Sweden actually received compensation, while the Drug Insurance Office was better utilized. Various reasons for these low reporting frequencies are discussed.