Epidemiology of invasive Streptococcus pneumoniae infections in adults in Finland.

Laboratory-based surveillance of invasive pneumococcal infections in adults in Finland from 1983 to 1992 identified 862 episodes of pneumococcal bacteraemia and 97 episodes of meningitis. The overall incidence of invasive pneumococcal infections was 9.1 per 100,000 for all adults per year, but 27.1, 35.8, and 44.5 per 100,000 in those aged 65 years or over, 75 years or over, and 85 years or over, respectively. Most (99.7%) of the pneumococcal strains were sensitive to penicillin. Ninety-five percent of the strains belonged to serogroups/types present in the 23-valent pneumococcal polysaccharide vaccine. Group/type distribution was different in patients aged 16-64 years compared to those 65 years or over (P < 0.001), in bacteraemia compared to meningitis (P < 0.001), and in the years 1983-7 compared to 1988-92 (P < 0.05).

Arcanobacterium haemolyticum and streptococcal pharyngitis in army conscripts.

Arcanobacterium haemolyticum was found in 1.4% and beta-haemolytic streptococci in 23% of throat cultures from army conscripts with sore throat (n = 498). 38% of the beta-haemolytic streptococci were of group A. Patients culture-positive for A. haemolyticum or beta-haemolytic streptococci had pharyngeal exudate, cervical lymphadenopathy and ear ache significantly more often--but cough less often--than culture-negative patients. The pharyngeal colonization rate of healthy conscripts (n = 232) by A. haemolyticum was 0.4% and by beta-haemolytic streptococci, 6.5%.

Role of aeromonas isolated from feces of Finnish patients.

Aeromonas species were isolated from 249/13,027 (1.9%) stool samples submitted to the Dept. of Bacteriology and Immunology, University of Helsinki, during 1 year, to be cultured for bacterial enteropathogens. Aeromonas was the third most common enteropathogen isolated, after campylobacter (3.6%) and salmonella (3.3%). Isolates and clinical information from 234 Aeromonas patients were available for further study. A. caviae (41%), A. hydrophila (27%), and A. veronii biovar sobria (22%) were the most frequent isolates. In 15% of the patients, other enteropathogens were found along with aeromonas. Only 2% of all aeromonas-positive patients were found to be asymptomatic, whereas no aeromonas isolates were detected in the stools of 343 asymptomatic individuals. Almost all (96%) patients with aeromonas in their feces had gastroenteritis. Patients infected with A. veronii biovar sobria had a shorter illness course and had more often travelled abroad. In conclusion, Aeromonas spp. were found to be a potential cause of diarrhea in Finnish patients.

Enteric Plesiomonas shigelloides infections in Finnish patients.

Plesiomonas shigelloides was isolated from 20/13,027 stool samples submitted for culture to the Department of Bacteriology and Immunology, University of Helsinki, in 1990. All except 2/20 Plesiomonas-positive patients had diarrhea; 13 patients had acute onset of illness after foreign travel and 5 patients had chronic diarrhea with symptoms lasting > or = 2 months. Travel destinations were outside Europe in most cases. In 12 cases Plesiomonas was isolated in pure culture and in 8 cases together with other enteropathogens. All isolates were susceptible to ciprofloxacin, doxycycline, trimethoprim and sulfamethoxazole, gentamicin, cephalexin, cefuroxime, ceftriaxone and cefixime.

Increased yields of pathogenic Yersinia enterocolitica strains by cold enrichment.

Yersinia strains recovered from routine stool cultures (n = 13,534) as well as clinical symptoms in the patients were analysed in order to establish whether enteric Yersinia enterocolitica strains recovered only after cold enrichment cultures shared the same pathogenicity markers and caused the same symptoms as strains from primary cultures. 93% of the 201 Yersinia isolates were Y. enterocolitica strains and 71% of these were of serotype O3. Nearly 40% of all Y. enterocolitica strains and 21% of serotype O3 strains were isolated only after 1 week's cold enrichment of stool specimens. Practically all Y. enterocolitica O3 strains, whether from primary or cold enrichment cultures, were pathogenic not only on the basis of the serotype but also on the basis of Congo-red uptake and calcium-dependent growth at 35 degrees C (CR-MOX test). The symptoms in patients with Y. enterocolitica O3 from primary and cold enrichment cultures were similar except that abdominal pains were more frequent (p < 0.05) in the former. Arthropathia, mesenteric lymphadenitis and erythema nodosum were detected in 15% of the patients with Yersinia isolates and were more frequent in patients with isolates from cold enrichment or without diarrhea.

Arcanobacterium haemolyticum and streptococcal pharyngitis.

Arcanobacterium haemolyticum was recovered from 0.5% of throat cultures of 3,922 patients seeking medical attention because of sore throat. Most of the patients positive for A. haemolyticum were 15-25 years old, and had fever (80%), lymphadenopathy (67%), pharyngeal exudate (69%) or skin rash (23%). In this age group, 2% of the throat cultures proved positive for A. haemolyticum. All A. haemolyticum strains were susceptible to penicillin, erythromycin, cephalexin and clindamycin, but resistant to trimethoprim/sulphamethoxazole. In half of the patients with A. haemolyticum it was the only bacterial pathogen isolated, while in the remainder, beta-haemolytic streptococci were also detected. As expected, beta-haemolytic streptococci were much more frequent than A. haemolyticum in the throat cultures.

Antimicrobial susceptibility of Arcanobacterium haemolyticum.

The susceptibilities of 138 clinical isolates of Arcanobacterium haemolyticum to 11 antimicrobial agents were tested. All strains were susceptible to phenoxymethylpenicillin, cephalosporins, erythromycin, azithromycin, clindamycin, vancomycin, doxycycline, and ciprofloxacin but were resistant to trimethoprim-sulfamethoxazole.

Azithromycin resistance in Campylobacter jejuni and Campylobacter coli.

The MICs of erythromycin, azithromycin and ciprofloxacin were determined for 60 human fecal isolates of Campylobacter. Of these, 30 strains selected on the basis of their resistance to erythromycin by disk diffusion were highly resistant to both erythromycin and azithromycin. Nine of these selected isolates were resistant to ciprofloxacin. The remaining 30 strains were non-selected, consecutive isolates of Campylobacter susceptible to erythromycin by disk diffusion and were shown to be two- to five-fold more susceptible to azithromycin than to erythromycin as determined by MIC testing.

Binding of bacterial adhesins to rat glomerular mesangium in vivo.

Two well characterized bacterial adhesins, the O75X fimbriae of Escherichia coli and the type-3 fimbriae of Klebsiellae, with in vitro affinities to type IV and V collagens, respectively, were used to test whether bacterial components with affinity for glomerular matrix could bind to glomeruli in vivo. The purified fimbrial proteins were injected into rats, and kidney samples were studied by immunofluorescence at two hours to nine months postinjection. The O75X, but not the type-3 fimbriae, formed mesangial deposits that persisted for months. Preincubation of the O75X fimbriae with type IV collagen significantly reduced the glomerular binding. The fimbrial deposits were extracellular, as anti-O75X IgG injected into rats bound to glomeruli. Proteinuria or histological damage could not be detected even after passive or active immunizations of the rats. The results demonstrate that bacterial adhesins may bind in vivo to and persist in glomeruli by their specific affinities. The results also indicate that additional factors provided by the bacteria or the host are needed for glomerular damage to take place.

Pharmacokinetics and transplacental passage of imipenem during pregnancy.

Imipenem pharmacokinetics were studied in early pregnancy (n = 7; length of gestation, 8.6 +/- 1.5 weeks, mean +/- standard deviation), in late pregnancy (n = 7; length of gestation, 38.7 +/- 1.4 weeks), and in the nonpregnant state (n = 6). A single dose of 500 mg of imipenem-cilastatin (1:1) was administered as a 20-min infusion. Multiple plasma and urine samples, as well as specimens of umbilical plasma and amniotic fluid from the pregnant subjects, were collected at frequent intervals for 8 h. Imipenem concentrations were assayed by specific microbiologic assay. The mean peak concentrations in plasma were 14.7 +/- 4.9, 14.9 +/- 5.2, and 43 +/- 28.3 micrograms/ml in early pregnancy, late pregnancy, and the nonpregnant state, respectively. The volumes of distribution were significantly larger during early pregnancy (0.98 +/- 0.45 liter/kg of body weight, P < 0.005) and late pregnancy (0.59 +/- 0.19 liter/kg, P < 0.05) than in the nonpregnant state (0.33 +/- 0.10 liter/kg), and total clearances from plasma were faster in early pregnancy (12.7 +/- 7.8 ml min-1 kg-1, P < 0.05) and late pregnancy (10.7 +/- 4.6 ml min-1 kg-1, P < 0.05) than in the nonpregnant state (5.77 +/- 1.19 ml min-1 kg-1). The mean concentrations in amniotic fluid were 0.07 +/- 0.01 and 0.72 +/- 0.85 micrograms/ml in early and late pregnancy. The mean umbilical venous and arterial drug concentrations were 1.72 +/- 1.22 and 1.64 +/- 1.22 micrograms/ml. The feto-maternal ratio at the time of cesarean section was 0.33 +/- 0.12. These results indicate that an adjustment of doses of imipenem may be required when treating pregnant women because of considerable changes in imipenem pharmacokinetics during pregnancy.

Bacterial vaginosis in early pregnancy and pregnancy outcome.

OBJECTIVE: We assessed the association between bacterial vaginosis in early pregnancy and adverse pregnancy outcome. METHODS: Vaginal swabs for bacterial culture, Gram stain, and Papanicolaou stain were taken at the first prenatal visit between 8-17 weeks' gestation in 790 healthy nulliparous women. RESULTS: Culture-proven bacterial vaginosis was detected in 169 of 790 women (21.4%), 167 (98.8%) of whom could also be identified by Gram stain. Papanicolaou smears were available from 299 women, among whom 101 had bacterial vaginosis on culture; of these 101, 78 (77.2%) could be detected by Papanicolaou stain. Of the 751 women whose clinical follow-up was completed, 42 had been treated for preterm uterine contractions (preterm labor), but only 17 delivered between 20-36 weeks' gestation (preterm birth). Premature rupture of membranes (PROM) occurred more than 6 hours before delivery in 80 cases (nine preterm and 71 term). Bacterial vaginosis in early pregnancy predicted preterm labor, preterm birth, or preterm PROM with a sensitivity of 41-67%, specificity of 79%, and negative predictive value of 96-99%, but the positive predictive value was low at 4-11%. However, bacterial vaginosis was associated with a 2.6-fold risk (95% confidence interval [CI] 1.3-4.9) for preterm labor, a 6.9-fold risk (95% CI 2.5-18.8) for preterm birth, and a 7.3-fold risk (95% CI 1.8-29.4) for preterm PROM. CONCLUSIONS: Bacterial vaginosis in early pregnancy can be detected reliably by Gram stain and, in most cases, by Papanicolaou smear. Although bacterial vaginosis is associated with preterm labor, preterm birth, and preterm PROM, the clinical usefulness of its assessment is limited because of the high rate of false-positive findings.

Pharmacokinetics of single-dose oral ciprofloxacin in infants and small children.

The pharmacokinetics of orally administered ciprofloxacin (CIP) was studied in seven infants aged 5 to 14 weeks and nine children aged 1 to 5 years, most of whom were Salmonella carriers. In each case, 15 mg of CIP per kg of body weight was given with water on an empty stomach, and timed serum samples were taken during the following 12 h. The elimination half-life of CIP was significantly (P less than 0.001) longer in the infants (2.73 +/- 0.28 h; mean +/- standard deviation) than it was in the children (1.28 +/- 0.52 h). The area under the serum CIP concentration-time curve (AUC) from time zero to infinity was 16.1 +/- 7.4 mg.h.liter-1 among the infants and 5.3 +/- 3.3 mg.h.liter-1 in the children (P less than 0.01). No significant differences in the maximum concentration in serum, time to maximum concentration in serum, or absorption half-life were observed between the two groups. In contrast, the mean residence time was twofold longer in the infants (4.6 h) than it was in the children (2.4 h; P less than 0.001). The findings suggest that elimination of CIP is particularly rapid in children who just have passed infancy; they may require doses at shorter time intervals than those required by infants or older children or adults. In general, an oral dose of 10 to 15 mg of CIP per kg three times daily seems appropriate for children aged 1 to 5 years.

Clinical presentation and outcome of listeriosis in patients with and without immunosuppressive therapy.

Seventy-four cases of systemic listeriosis occurring from 1971 to 1989 in the greater Helsinki area in Finland are reviewed with a special interest in the effect of preceding immunosuppressive therapy on the clinical presentation. Of these patients, 66% had an underlying disease, most commonly malignancy, diabetes mellitus, or renal transplantation, and 43% had received immunosuppressive therapy within 1 week before onset of listeriosis. Bacteremia and central nervous system infections (both in 43% of cases) were the most common clinical entities. The percentage of patients with meningitis was not greater among immunosuppressed patients (13/32, 41%) than among patients with underlying diseases not treated with immunosuppressive agents (9/16, 56%) or among previously healthy nonpregnant hosts (7/11, 64%). Immunosuppressed patients did not die more frequently than did those with underlying diseases not treated with immunosuppressive therapy (case fatality rate, 29% vs. 38%, respectively). However, all previously healthy non-neonatal patients survived, whereas 32% (15/47) of those with any kind of underlying disease succumbed.

Pneumococcal bacteraemia during a recent decade.

We retrospectively reviewed 159 episodes of bacteraemic pneumococcal infection in 157 adult patients at the Helsinki University Central Hospital during two periods between 1976 and 1979 and 1986 and 1989. We looked especially at changes in underlying diseases and prognostic factors. The overall case fatality rate was 21% and there was a small diminishing trend in that rate from 28% (16/58) in the late 1970s to 17% (17/101) in the late 1980s. The patients who died in the late 1980s were younger than those who died in the earlier period. The most common underlying factors were alcohol abuse, cardiovascular diseases and chronic obstructive pulmonary diseases. Old age was neither a predisposing factor nor did it predict the outcome. No significant changes in underlying diseases or prognostic factors were noted during the two periods studied except a small decrease in connective tissue diseases as underlying conditions. The factors related to increased fatality included hepatic cirrhosis, a combination of pneumonia and meningitis, complications such as shock, respiratory insufficiency, central nervous system disorders and circulatory acidosis, and laboratory findings such as thrombocytopenia, absence of leucocytosis and increased amounts of serum creatinine, aspartate aminotransferase and alanine aminotransferase on admission to the hospital. Previous splenectomy and malignant diseases were not associated with higher mortality. The thrombocytopenia at the time of positive blood culture and the circulatory acidosis as a complication seemed to be independently the most useful predictive factors for a fatal outcome using multivariate logistical regression analysis after adjustment to classic risk factors.

Evaluation of the E test in testing susceptibility of Pseudomonas aeruginosa to tobramycin.

The E test, a new technique for measuring MICs of antimicrobial agents with the ease of disc diffusion tests, was evaluated in testing the susceptibility of 94 clinical isolates of Pseudomonas aeruginosa to tobramycin. The use of the E test was found acceptable; 93% of the MIC results were within one log2 dilution step and 100% were within two log2 dilution steps when the MICs obtained by the E test were compared to those obtained by the conventional agar dilution method. When the E test was compared to the broth microdilution method the corresponding figures were 84% and 100%, respectively.

Role of metronidazole resistance in therapy of Helicobacter pylori infections.

Susceptibility to metronidazole was determined by disk diffusion tests for 559 strains of Helicobacter pylori isolated from patients. The overall metronidazole resistance was 26%. In males metronidazole-resistant strains made 18% of all H. pylori strains, and in females the corresponding figure was 40% (P less than 0.001). MICs of metronidazole were determined for H. pylori strains from 86 patients undertaking triple therapy, i.e., treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. Of the nonresponders who remained culture positive despite the therapy, 69% had strains with metronidazole MICs of greater than or equal to 32 micrograms/ml before the therapy, and all nonresponders had metronidazole-resistant strains after the therapy. Metronidazole resistance was, however, also found in 27% of responders before therapy. To find whether the MICs of metronidazole for H. pylori strains remained constant for longer periods, consecutive isolates sampled several years apart from the same patients were tested in parallel and no changes in the MICs were found. H. pylori was successfully eradicated by the triple therapy from 91% of patients with metronidazole-susceptible pretreatment strains and from 63% of patients with metronidazole-resistant strains before the therapy (P less than 0.01). Although resistance to metronidazole has a significant role in treatment failures in H. pylori infections, high eradication rates can be achieved with the use of the present triple therapy even in populations with a high overall metronidazole resistance rate.

Emergence of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli in subjects from Finland.

The in vitro susceptibilities of 102 human campylobacter strains isolated between 1978 and 1980 and 100 strains isolated in 1990 to ciprofloxacin, norfloxacin, erythromycin, gentamicin, and doxycycline were examined. The biotypes and heat-stable serotypes of the strains as well as antimicrobial treatments and travel history of the campylobacter-positive patients were also studied. The results indicated that susceptibility to erythromycin, gentamicin, and doxycycline has remained the same during the past 10 years. No gentamicin-resistant strains were found. Resistance to erythromycin was 3% in both groups of strains. However, the number of norfloxacin-resistant strains increased from 4 to 11% in the follow-up period, and ciprofloxacin-resistant strains, which had not occurred 10 years ago, composed 9% of the strains isolated in 1990. Thus, the increase of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli has been significant in Finland in the past 10 years.