Azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children.

A total of 108 children aged 4-17 years were randomized to receive 7 days of azithromycin (10 mg/kg/day; maximum, 500 mg/day) or ceftriaxone (75 mg/kg/day; maximum, 2.5 g/day), to assess the efficacy of the agents for the treatment of uncomplicated typhoid fever. Salmonella typhi was isolated from the initial cultures of blood samples from 64 patients. A total of 31 (91%) of the 34 patients treated with azithromycin and 29 (97%) of the 30 patients treated with ceftriaxone were cured (P>.05). All 64 isolates were susceptible to azithromycin and ceftriaxone. Of the patients treated with ceftriaxone, 4 subsequently had relapse of their infection. No serious side effects occurred in any study subject. Oral azithromycin administered once daily appears to be effective for the treatment of uncomplicated typhoid fever in children. If these results are confirmed, the agent could be a convenient alternative for the treatment of typhoid fever, especially in individuals in developing countries where medical resources are scarce.

Azithromycin versus ciprofloxacin for treatment of uncomplicated typhoid fever in a randomized trial in Egypt that included patients with multidrug resistance.

To compare clinical and bacteriological efficacies of azithromycin and ciprofloxacin for typhoid fever, 123 adults with fever and signs of uncomplicated typhoid fever were entered into a randomized trial. Cultures of blood were positive for Salmonella typhi in 59 patients and for S. paratyphi A in 3 cases; stool cultures were positive for S. typhi in 11 cases and for S. paratyphi A in 1 case. Multiple-drug resistance (MDR; resistance to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole) was present in isolates of 21 of 64 patients with positive cultures. Of these 64 patients, 36 received 1 g of azithromycin orally once on the first day, followed by 500 mg given orally once daily on the next 6 days; 28 patients received 500 mg of ciprofloxacin orally twice daily for 7 days. Blood cultures were repeated on days 4 and 10 after the start of therapy, and stool cultures were done on days 4, 10, and 28 after the start of therapy. All patients in both groups improved during therapy and were cured. Defervescence (maximum daily temperatures of

Tuberculosis meningitis, Abbassia Fever Hospital-Naval Medical Research Unit No. 3-Cairo, Egypt, from 1976 to 1996.

A total of 1,430 patients with the presumptive diagnosis of tuberculous meningitis were admitted to the U.S. Naval Medical Research Unit No. 3/Abbassia Fever Hospital in Cairo, Egypt from January 1976 to January 1996. Diagnosis was confirmed by culture of the mycobacteria from the cerebrospinal fluid CSF of 857 patients and these patients are included in the final analysis. There were 497 males and 360 females. The patients ranged in age from five months to 55 years. The number of patients admitted during the months of March, April, and May were more than double those admitted during October, November, and December. The duration of symptoms prior to admission ranged from seven to 90 days (mean = 29.5 days). Upon admission, 4% of the patients were alert, 34% were drowsy, and 62% were in a coma. Of the 857 patients studied, 490 (57%) died, 256 (30%) recovered completely, and 11 (13%) recovered with sequelae. The mortality and neurologic sequelae were directly related to the stage of disease and duration of symptoms prior to admission. Mortality was significantly lower in patients admitted in stage II and or with short duration of disease compared with those in stage III and or with prolonged duration of symptoms prior to admission. The use of dexamethasone in patients with tuberculous meningitis significantly reduced the ocular complications that occur in these patients and also significantly reduced the fatality rate.

The value of the tuberculin skin test in patients with tuberculous meningitis.

To determine the clinical utility of the tuberculin purified protein derivative (PPD) skin test in patients suspected of having tuberculous meningitis (TBM), the test was applied on admission to 180 patients suspected of having tuberculous meningitis and to 50 patients with proven bacterial meningitis admitted to the Abbassia Fever Hospital, Cairo, Egypt, during the period 1987 to 1989. Admission tuberculin positivity in evaluated groups revealed the following: overall suspect TBM cases--17% (31/180), culture-confirmed TBM cases--19% (16/83), and culture-confirmed acute bacterial meningitis cases--14% (7/50). Repeat PPD skin test at 60 days in surviving presumptive/confirmed TBM cases revealed a significant increase in tuberculin positivity to 62% (58/93) from admission (p < 0.001). Evaluation of PPD positivity by clinical stage of TBM revealed 36% positivity in alert patients as compared to 12% positivity in comatose patients (p = 0.01). Admission tuberculin skin testing as a diagnostic aid for clinical management of tuberculous meningitis is of limited utility in our study population because of the high prevalence of tuberculin positivity in the Egyptian population (potential false positive correlation with the acute presentation) and the advanced stage of TBM at presentation to Egyptian public hospitals (potential false negative correlation).

Short course chemotherapy with cefixime in children with multidrug-resistant Salmonella typhi Septicaemia.

Increasing prevalence of multidrug-resistant (MDR) Salmonella typhi strains in pediatric cases of typhoid fever and chemotherapy restrictions in children, such as fluoroquinolones, require ongoing clinical evaluations of different antibiotic regimens. Previously reported clinical trials with oral cefixime therapy given as a 12-day regimen (20-30 mg/kg divided twice daily) demonstrated both safety and efficacy. An open trial was undertaken to investigate a short course (8-day) regimen of oral cefixime in an Egyptian public fever hospital. Eighty children were initially enrolled with blood culture confirmation in 60 children. Clinical cure was documented in 57 (95 per cent) with three children requiring a change in antibiotic regimen due to therapeutic failure and one child with culture-confirmed relapsed 21 days post-therapy. All S. typhi isolates were sensitive to cefixime as measured by disk diffusion. Cefixime was well-tolerated with only mild side-effects, including nausea/vomiting (8 per cent) and abdominal cramping with loose stools (6 per cent), which may have been secondary to typhoid fever. Cefixime given in a short 8-day course is safe and effective in the management of MDR typhoid fever in children.

Evaluation of the response of human humoral antibodies to Salmonella typhi lipopolysaccharide in an area of endemic typhoid fever.

Because of the limited value of Widal's test in the diagnosis of typhoid fever in areas of endemicity, individual serum levels of IgM, IgA, IgG, and IgG subclass antibodies to Salmonella typhi lipopolysaccharide were evaluated in samples collected in Egypt. The study involved 106 febrile patients, including 40 patients for whom cultures were positive for S. typhi and 66 patients for whom diseases other than typhoid were diagnosed. Multivariate regression modeling revealed that detection of the combination of IgA, IgG, and IgG2 correlated best, although not perfectly (adjusted r(2) = 68), with a positive culture; the sensitivity and specificity of testing for IgA, IgG, and IgG2 (i.e., all three tests positive vs. all three tests negative) were 91.7% and 98.1%, respectively. These results suggested that testing for IgA, IgG, and IgG2 in combination is of diagnostic value for S. typhi infection.

Comparison of the efficacy, safety and cost of cefixime, ceftriaxone and aztreonam in the treatment of multidrug-resistant Salmonella typhi septicemia in children.

An increase in the incidence of Salmonella typhi strains resistant to chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole causing enteric fever in Egyptian children stimulated the evaluation of alternative drugs. Children with positive blood cultures were treated with cefixime, ceftriaxone or aztreonam, and the efficacy, safety and cost of these regimens were evaluated and compared. Cefixime (7.5 mg/kg) was given orally twice daily to 50 children for 14 days, ceftriaxone (50 to 70 mg/kg) was given im once daily for 5 days to 43 children and aztreonam (50 to 70 mg/kg) was given im every 8 hours for 7 days to 31 children. Children in the 3 groups were comparable with regard to age, sex, duration and severity of illness before admission. All children were cured. A significant difference (P < 0.05) in duration of treatment before becoming afebrile seemed to favor ceftriaxone (3.9 days) over aztreonam (5.5 days) and cefixime (5.3 days). During the 4-week follow-up period relapses occurred in 3 (6%) children in the cefixime group, in 2 (5%) in the ceftriaxone group and in 2 (6%) in the aztreonam group. Safety and efficacy were comparable for all 3 drugs. Ceftriaxone was most cost-effective on an inpatient basis, because of a more rapid clinical cure, and cefixime was the most cost-effective on an outpatient basis, because of drug cost.

Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children--implications for vaccine strategies.

Streptococcus pneumoniae is a leading cause of fatal bacterial pneumonia in young children. Pneumococcal polysaccharide vaccines have not been promoted for use in young children because many constituent serotypes are not immunogenic in children < 2 years old. Conjugating pneumococcal polysaccharide epitopes to a protein carrier would likely increase vaccine immunogenicity in children. We reviewed published and unpublished pneumococcal serotype and serogroup data from 16 countries on 6 continents to determine geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates among children and to estimate coverage of proposed and potential pneumococcal conjugate vaccine formulas. The most common pneumococcal serotypes or groups from developed countries were, in descending order, 14, 6, 19, 18, 9, 23, 7, 4, 1 and 15. In developing countries the order was 6, 14, 8, 5, 1, 19, 9, 23, 18, 15 and 7. Development of customized heptavalent vaccine formulas, one for use in all developed countries and one for use in all developing countries, would not provide substantially better coverage against invasive pneumococcal disease than two currently proposed heptavalent formulas. An optimal nanovalent vaccine for global use would include serotypes 1, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Geographic and temporal variation in pneumococcal serotypes demonstrates the need for a species-wide pneumococcal vaccine.

Cefixime in the treatment of enteric fever in children.

Cefixime in a dose 20 mg/kg/day, orally, divided into two doses 12 h apart for a minimum of 12 days, was administered to 50 children with proven S. typhi septicaemia. Forty four of the patients were infected with strains of S. typhi resistant to multiple antibiotics including chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole. All patients responded rapidly to treatment and were cured clinically and bacteriologically. Fever subsided within a mean of 5.3 days (range 3-8 days). Only two of the 50 patients treated relapsed during the 8 week follow-up period. No serious adverse reactions attributable to the drug were observed. Cefixime proved to be an effective oral drug in this open treatment trial and was associated with minimal side effects. It may provide a therapeutic alternative to the treatment of Salmonella infection with organisms multi-resistant to the standard drug regimens. Its oral formulation may provide an efficient alternative to parenteral therapy in less severely ill patients who can tolerate oral feeding.

Meningitis and encephalitis at the Abbassia Fever Hospital, Cairo, Egypt, from 1966 to 1989.

A total of 7,809 patients with meningitis or encephalitis were admitted to the Abbassia Fever Hospital in Cairo, Egypt from November 1, 1966 to April 30, 1989. The etiology was Neisseria meningitidis (mostly group A) in 27.3% of the patients, Mycobacterium tuberculosis in 19.7%, Streptococcus pneumoniae in 7.3%, and Haemophilus influenzae in 4.1%. Almost 27% of the cases had purulent meningitis but without detectable etiology; however, the epidemiologic data suggest that most of these had meningococcal meningitis. Encephalitis was suspected in 12.5% of the patients. Most of the meningococcal, pneumococcal, and Haemophilus cases occurred during the winter months. The number of meningococcal and culture-negative purulent cases per year reached a maximum three times during the 22.5 years of this study. There were more males than females in all etiologic groups, with the ratio for the total patient population being 1.6:1. The average age ranged between 11.7 and 16.5 years for all groups except for Haemophilus patients, who had a mean age of 2.5 years. The mortality rate was almost 55% for tuberculous patients and was approximately 40% for both pneumococcal and Haemophilus patients; it was 8.5% in patients with meningococcal disease.

Evaluation of hepatic fibrosis after oxamniquine therapy of murine schistosomiasis.

Chemical and histological indices of liver fibrosis were measured after eight, 18 and 28 weeks in mice infected with Schistosoma mansoni and treated at eight weeks with oxamniquine, in mice infected with S. mansoni and not treated and in mice not infected with S. mansoni. Total worm burdens and liver egg counts were determined in the infected mice to determine severity of infection. Treatment with oxamniquine resulted in near total eradication of S. mansoni worms after 10 weeks and in their complete killing and marked reduction of eggs in the liver at 10 and 20 weeks. Liver fibrosis 10 weeks after oxamniquine treatment was not significantly different than in the untreated, infected group but there was no progression between 10 and 20 weeks after oxamniquine treatment. Fibrosis did however increase between 10 and 20 weeks in the untreated infected group. In the murine model, oxamniquine is an effective treatment for S. mansoni and prevents progression of liver fibrosis.

Aztreonam compared to chloramphenicol in the treatment of enteric fevers.

Fifty-seven patients, twenty-six males and thirty-one females, aged 6 to 50 years (mean 12.6 years) with proven Salmonella typhi or S. paratyphi A septicaemia, were treated in an open randomized parallel study with either aztreonam or chloramphenicol. Aztreonam was given intramuscularly at a level of 50 to 80 mg/kg body weight per dose every 8 h for 7 days to thirty patients. Chloramphenicol was given orally in a dose of 50 to 70 mg/kg body weight every 6 h for 12 days to twenty-seven patients. All patients responded rapidly to treatment, becoming afebrile and asymptomatic within 5.5 to 6.4 days. Only one patient on aztreonam relapsed following treatment, whereas three patients relapsed after chloramphenicol treatment. There were no serious side effects with either drug.

Detection of IgM antibodies to Neisseria meningitidis group A polysaccharide in meningitis patients by direct and antibody capture enzyme-linked immunosorbent assays.

Serum specimens obtained from culture-positive group A meningococcal meningitis patients in Cairo, Egypt were tested for immunoglobulin M (IgM) antibodies to Neisseria meningitidis group A polysaccharide by direct and IgM capture enzyme-linked immunosorbent assays (ELISAs). Sera from patients with meningitis caused by other bacteria were used as negative control specimens. The IgM antibodies to this antigen were detected by direct ELISA in 93% of 58 specimens obtained from patients with group A meningococcal disease three or more days after hospital admission, and by IgM capture ELISA in 83% of 60 such specimens. Sixteen percent of 25 specimens obtained three or more days after admission from negative control patients were positive by direct ELISA, and 4% were positive by IgM capture ELISA. The correlation coefficient of the results with the two assays was 0.85.

Dexamethasone adjunctive treatment for tuberculous meningitis.

During a 5-year period, 280 of 2010 patients admitted to the meningitis ward of a referral hospital in Cairo, Egypt, were clinically diagnosed as having tuberculous meningitis and were treated with either antituberculous chemotherapy and dexamethasone or antituberculous chemotherapy alone. Fatality rates and neurologic sequelae were compared for the 2 treatment groups in the 160 patients who had cerebrospinal fluid cultures positive for Mycobacterium tuberculosis. The overall mortality rate of 51% reflects the delay in receiving appropriate therapy (79% with symptoms for more than 2 weeks) and the severity of illness on admission (56% in coma, 39% drowsy). The fatality rate was significantly lower in the group receiving dexamethasone (43% vs. 59%, P less than 0.05), particularly in the drowsy patients (15% vs. 40% P less than 0.04), and in patients surviving long enough to receive at least 10 days of treatment (14% vs. 33%, P less than 0.02). Development of neurologic complications after initiation of therapy (4 vs. 10) and permanent sequelae (6 vs. 13) were significantly lower in the dexamethasone-treated group (P less than 0.02).

A review of the treatment of bacterial meningitis.

This is review of our experience in the treatment of meningitis carried out at the Naval Medical Research Unit No. 3 (NAMRU-3), Cairo, Egypt since 1967. We have demonstrated that the serum and cerebrospinal fluid concentrations of ampicillin and its efficacy when used in the treatment of meningitis are comparable whether they are administered intravenously or intramuscularly. The third generation cephalosporin ceftriaxone was found to be very safe and effective when administered intramuscularly once a day in the treatment of the different types of acute bacterial meningitis. Aztreonam given intramuscularly was successful in the treatment of Gram-negative meningitis caused by multi-resistant organisms. The fatality rates and morbidity were significantly reduced in patients with meningitis when dexamethasone was given in conjunction with antibacterial chemotherapy.

Epidemiology, prevalence and clinical diagnosis of meningitis at Abbassia Fever Hospital, Cairo, 1966-1989.

The United States Naval Medical Research Unit No. 3 and the Abbassia Fever Hospital in Cairo, Egypt have together diagnosed and treated 7809 patients admitted to a meningitis ward since 1966. Aetiological diagnosis was based on clinical evaluation and laboratory studies. Marked increases in annual admissions in 1970-1972, 1980-1982 and 1987-1988 were related to increases in admissions due to meningococcal disease, while in 1977-1981 the increase was due to encephalitis related to Rift Valley fever. Better, rapid diagnostic procedures are needed to enable effective treatment to be given earlier and to reduce mortality rates.

Laboratory diagnosis of bacterial meningitis.

This overview summarizes studies conducted since 1970 on the laboratory diagnosis of bacterial meningitis at the Naval Medical Research Unit No. 3. These investigations demonstrated that counterimmunoelectrophoresis (CIE), agglutination of sensitized staphylococcal cells or latex particles, and enzyme-linked immunosorbent assay (ELISA) effectively detect and identify specific antigens in the cerebrospinal fluid of patients with meningococcal, pneumococcal, and Haemophilus meningitis. ELISA was the most sensitive of these methods and CIE the least sensitive. ELISA was also used to measure antibodies to meningococcal outer membrane protein antigens in patients. Finally, high rates of group A meningococcal nasopharyngeal carriage were found in group A meningococcal meningitis patients and populations associated with group A patients, but not in populations that were not associated with group A disease.