Changing epidemiology of group B streptococcal infections among adults in Iceland: 1975-2014.

We studied the bacterial characteristics and incidence of invasive infections caused by group B streptococci (GBS) in adults in Iceland in 1975-2014. A total of 145 isolates were characterized by serotyping, antimicrobial susceptibility, multilocus sequence typing and surface protein gene profiling. Disease incidence increased during the studied period (p <0.001), reaching 2.17 cases/100 000 person-years in 2013-14. Overall, serotype Ia was the most frequently found (23%), but serotypes Ib, II, III and V showed similar prevalence (14%-17%). Although there were notable changes in the proportion of most serotypes during the study period, only the decline of serotype III was statistically supported (p = 0.003) and was reflected in a decrease of clonal complexes CC17 and CC19 that included most serotype III isolates (p <0.04). On the other hand, the increase in frequency of CC1 was caused by two lineages expressing distinct serotypes: ST1/V/alp3 and ST196/IV/eps. Underlying the relative stability of serotype Ia were major changes in the lineages expressing this serotype, with an increase in the relative importance of CC23, including both ST23/Ia/eps and ST24/Ia/bca lineages, and a decrease in CC7. Nine cases of invasive GBS disease were caused by ST7, of possible zoonotic origin. All isolates were susceptible to penicillin. Rates of erythromycin and clindamycin resistance were 8.3% and 9.7%, respectively. An over-representation of resistance solely to clindamycin was associated with the unusual lsaC gene and serotype III ST19/rib lineage (p <0.001).

Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012.

Epidemiology and clinical characteristics of invasive Group A streptococcal infections (IGASI) are highly variable. Long-term studies are needed to understand the interplay between epidemiology and virulence. In a population-based study of IGASI in Iceland from 1975 to 2012, 288 cases were identified by positive cultures from normally sterile body sites. Charts were reviewed retrospectively and emm-types of viable Streptococcus pyogenes isolates (n=226) determined. Comparing the first and last decade of the study period, IGASI incidence increased from 1.09 to 3.96 cases per 100,000 inhabitants per year. The most common were emm types 1 (25%), 28 (11%) and 89 (11%); emm1 strains were most likely to cause severe infections. Infections in adults were significantly more likely to be severe during the seasonal peak from January to April (risk ratio: 2.36, 95% confidence interval: 1.34­4.15). Significant seasonal variability in severity was noted among patients with diagnosis of sepsis, respiratory infection and cellulitis, with 38% of severe infections in January to April compared with 16% in other months (p<0.01). A seasonal increase in severity of IGASI suggested that generalised seasonal increase in host susceptibility, rather than introduction of more virulent strains may play a role in the pathogenesis of these potentially fatal infections.

Molecular epidemiology of late recurrent candidaemia--a population-based study in Iceland.

Candidaemia is associated with high patient mortality. Among those who survive an initial episode of candidaemia, the incidence of recurrent episodes has been incompletely defined. All patients in Iceland with candidaemia in 1980-2008 were identified, and clinical information was reviewed. Episodes of candidaemia in the same patient were considered to be separate if they occurred ≥ 1 month apart or were caused by different Candida species. The isolates were genotyped by using PCR fingerprinting, and antifungal susceptibility was determined. During the 29-year period, candidaemia was diagnosed in 307 patients in Iceland, 298 of whom (97.1%) had a single episode. Overall, 206 patients survived >1 month from the first episode and were therefore at risk of recurrence, yielding 1062 patient-years of observation in the survivors. Of those, nine (4.4%) later developed recurrent candidaemia. The median time between recurrences was 6 months (range, <1 month to 14 years). Patients with late recurrences were younger (p 0.012) and more likely to have underlying gastrointestinal diseases than patients with single episodes (55.6% vs. 18.5%, respectively; p 0.017). The recurrences were caused by identical Candida sp. genotypes in two of 13 cases (15%), but by different species or dissimilar genotypes in eight of 13 (62%); isolates were missing in three cases. In conclusion, late recurrent candidaemia was a relatively rare event, and younger patients with gastrointestinal disorders were more prone to recurrent infections. The majority of late recurrences represented re-infections with new Candida strains that were susceptible to common antifungal agents.

Evolving epidemiology of invasive Haemophilus infections in the post-vaccination era: results from a long-term population-based study.

Historically, Haemophilus influenzae (Hi) serotype b (Hib) caused most invasive Haemophilus infections worldwide, mainly in children. In 1989 routine childhood vaccination against Hib was initiated in Iceland. We conducted a population-based study of all patients in the country with Haemophilus spp. isolated from sterile sites (n = 202), from 1983 to 2008. Epidemiology, clinical characteristics of the infections and serotypes of the isolates were compared during the pre-vaccination (1983-1989) and post-vaccination era (1990-2008). Following the vaccination, the overall incidence of Hib decreased from 6.4 to 0.3/100,000 per year (p <0.05) whereas the incidence did not change significantly for infections caused by Haemophilus sensu lato not serotype b, hereafter referred to as non-type b Hi (0.9 vs 1.2, respectively). The most frequent diagnosis prior to 1990 was meningitis caused by Hib, which was subsequently replaced by pneumonia and bacteraemia caused by non-type b Hi. Most commonly, non-type b Hi were non-typeable (NTHi; 40/59), followed by Hi serotype f (14/59) and Hi serotype a (3/59). Pregnancy was associated with a markedly increased susceptibility to invasive Haemophilus infections (RR 25.7; 95% CI 8.0-95.9, p <0.0001) compared with non-pregnant women. The case fatality rate for Hib was 2.4% but 14% for non-type b Hi, highest at the extremes of age. Hib vaccination gives young children excellent protection and decreases incidence in the elderly due to herd effect in the community. Replacement with other species or serotypes has not been noted. Pregnant women are an overlooked risk group.

The importance of strain variation in virulence of Candida dubliniensis and Candida albicans: results of a blinded histopathological study of invasive candidiasis.

The pathogenic yeast Candida dubliniensis is increasingly reported as a cause of systemic fungal infections. We compared the virulence of 9 clinical bloodstream isolates of C. dubliniensis with 3 C. albicans isolates in a murine model of invasive candidiasis. Quantification of organisms and inflammatory changes in kidneys of infected animals were evaluated in a blinded, systematic manner. Average 7-day mortality among animals infected with C. dubliniensis was 21.0% (33/157 animals; range for strains: 0-57.1%); and with C. albicans 23.2%, (23/99 animals; range for strains: 6.7-85.0%) (p 0.65). Greater strain variation was noted within species than between the two species. Both species comprised strains of either high or low virulence, and six of the nine C. dubliniensis strains showed negligible virulence. Colony counts determined on samples from liver and kidneys did not differ between species. According to histopathological analysis, C. dubliniensis produced significantly lower levels of hyphae than C. albicans (p <0.001). Candida albicans caused a greater inflammatory response in kidneys (p <0.001) and was more commonly associated with granulomatous inflammation (p 0.003) and greater mononuclear infiltrate (p <0.001). According to multivariate analysis, increasing tissue burden of both hyphal forms (p 0.032) and yeasts (p 0.016) was independently associated with death, whereas higher levels of mononuclear cells were protective (p <0.001). The results suggest a great overlap between the virulence properties of C. dubliniensis and C. albicans. Both yeast and hyphal forms are independently associated with mortality, suggesting similar virulence for both. The source of the fungal isolates may be a neglected confounding factor in virulence studies in animal models.

Risk factors and outcome in ICU-acquired infections.

BACKGROUND: Nosocomial infections are common in intensive care units (ICU). The objectives of this study were to determine risk factors of ICU-acquired infections, and potential mortality attributable to such infections. METHODS: An observational study was performed in a 10-bed multidisciplinary ICU. For a period of 27 months, all patients admitted for >or=48 h were included. Infections were diagnosed according to Centers for Disease Control and Prevention definitions. Airway colonization was explored by molecular typing. Risk factors for infection were determined by multivariable logistic regression. Survival was analyzed with time-varying proportional hazards regression. RESULTS: Of 278 patients, 81 (29%) were infected: urinary tract infections in 39 patients (14%), primary bloodstream infections in 25 (9%), surgical site infections in 22 (8%) and pneumonia in 21 (8%). Of the total of 147 episodes, Gram-negative bacilli were isolated in 90, Gram-positive cocci in 49 and Candida sp. in 25. Risk factors for pneumonia were mechanical ventilation [odds ratio (OR=7.9, CI 1.8-35), lack of enteral nutriment (OR=8.0, CI 1.4-45) and length of time at risk (OR=1.8, CI 1.2-2.8), while gastric acid inhibitors did not affect the risk (OR=0.99, CI 0.32-3.0). Transmission of bacteria from the stomach to the airway was not confirmed. The risk of death was increased as patients were infected with pneumonia [hazard ratio (HR)=3.6; CI: 1.6-8.1], or primary bloodstream infection (HR=2.5; CI: 1.2-5.4), independent of age and disease severity. CONCLUSIONS: Mortality was increased by ICU-acquired pneumonia and primary bloodstream infections. Our findings did not support the gastro-pulmonary hypothesis of ICU-acquired pneumonia. The proposition that blood transfusions increase the risk of ICU-acquired nosocomial infections was not supported.

Nationwide study of recurrent invasive pneumococcal infections in a population with a low prevalence of human immunodeficiency virus infection.

Recurrent invasive infections caused by Streptococcus pneumoniae are rare, and often considered to be indicative of serious underlying illness. However, the prevalence of this problem, and the relevance of specific predisposing conditions, can be hard to assess, since many of the studies are based on specific risk groups. A population-based study of recurrent invasive pneumococcal disease in Iceland during the 30-year period 1975-2004 was performed. Clinical information, including mortality and vaccine use, was analysed retrospectively. Invasive pneumococcal isolates were serotyped and susceptibility testing was performed. During this period, 36 (4.4%) of 819 patients who survived an initial infection experienced recurrence, with a median time between episodes of 9.7 months. Pneumonia with bacteraemia was the most common clinical diagnosis (48% of cases), followed by bacteraemia without a clear focus (21%) and meningitis (13%). Most (94%) of the patients had identifiable predisposing conditions, most commonly, multiple myeloma in adults, and antibody deficiencies in children. Compared with children, adults were more likely to present with pneumonia (65% vs. 18%; p 0.0001). No significant change in the 30-day mortality rate was observed during the three decades of the study. Only 26% of eligible patients received pneumococcal vaccination. Patients with recurrent invasive pneumococcal disease should be investigated thoroughly for underlying diseases. Greater use of pneumococcal vaccines should be encouraged among high-risk patients. More effective preventive and therapeutic measures are needed to improve outcomes.

The improved survival of experimental animals fed with fish oil is suppressed by a leukotriene inhibitor.

Fish oil is believed to alter the immune response and improve survival after infections in experimental animals. This effect may be due to altered production of the leukotrienes (LT). We, therefore, performed a study in order to evaluate whether the effect of fish oil on the immune response of experimental animals is mediated through altered production of the LT. Female NMRI mice in four groups were fed with fish oil, fish oil with 5-lipoxygenase (5-LO) inhibitor (Zileuton, Abbott Laboratories, Chicago, IL, USA), corn oil or corn oil with 5-LO inhibitor. After 6 weeks, the mice were infected with Klebsiella pneumoniae and the survival was monitored. The experiment was performed twice. Analysis was performed mainly on data pooled from both experiments. The survival of the groups fed with fish oil was increased, compared to that of all the other groups and when compared to the groups fed with fish oil with 5-LO inhibitor (log-rank test) the difference was significant (P = 0.007). It has been postulated that the effect of fish oil on the immune system is mediated through altered production of LT. In our study, blocking of the production of the LT eliminated the beneficial effects of fish oil. Our results are in concord with the hypothesis that the effect of fish oil is, at least partly, mediated through altered production of LT.

Penicillin pharmacodynamics in four experimental pneumococcal infection models.

Clinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP). The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits. Two multidrug-resistant isolates of Streptococcus pneumoniae type 6B were used, one for which the penicillin MIC was 0.016 microg/ml and the other for which the penicillin MIC was 1.0 microg/ml. Two additional strains of PNSP were studied in the rabbit. The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (C(max)s) and times that the concentrations were greater than the MIC (T(>MIC)s). The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits. Similar pharmacodynamic effects were observed in all models. In the mouse models bactericidal activity depended on the T(>MIC) and to a lesser extent on the Cmax/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC. Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (approximately 6 log10 CFU/ml), followed by the thigh (approximately 3 log10 CFU/thigh), and being the lowest in the lung (approximately 1 log10 CFU/lung). In the rabbit model the maximal effect was approximately 6 log10 CFU/ml after 24 h. In the mouse models bactericidal activity became marked when T(>MIC) was > or =65% of the experimental time and C(max) was > or =15 times the MIC, and in the rabbit model bactericidal activity became marked when T(>MIC) was > or =35%, Cmax was > or =5 times the MIC, and the AUC at 24 h/MIC exceeded 25. By optimization of the Cmax/MIC ratio and T(>MIC), the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.

[The effect of dietary fish oil on bacterial growth in vivo.].

OBJECTIVE: Epidemiological studies have indicated that high intake of w-3 fatty acids influence various diseases such as cardiovascular diseases and autoimmune disorders. These fatty acids are essential in the diet since the body can not form them de novo. Fish oil is rich in w-3 fatty acids but the w-3 content of vegetable oil is low. The research group has shown increased survival of mice fed cod liver oil enriched diet versus mice fed corn oil enriched diet when infected with Klebsiella pneumoniae intramuscularly. In the present study we investigated the effect of dietary fish oil on bacterial growth in vivo. MATERIAL AND METHODS: Mice were fed fish oil enriched diet and a control group was fed corn oil enriched diet for six weeks and then the mice were infected with Klebsiella pneumoniae intramuscularly. The mice were sacrificed at various time intervals and bacteria were counted in blood and in the infected muscle. RESULTS: The bacteria count in blood and tissue was not significantly different between the two groups although a trend was noted towards more growth in the control group. CONCLUSIONS: We conclude that fish oil does not significantly affect bacterial growth in vivo. Hopefully, future research will reveal the pathophysiological effect of fish oil.

[Fungemia and other invasive fungal infections in Icelandic children. A nationwide study.].

INTRODUCTION: Invasive fungal infections are increasing in incidence. Among those who are at increased risk of fungal blood stream infections (fungemia) and disseminated fungal infections are premature infants and immunosuppressed children. These infections are associated with high morbidity and mortality. Invasive fungal infections have not yet been studied in Iceland. MATERIAL AND METHODS: We studied all cases of fungemia and/or disseminated fungal infections in Icelandic children (16 years) during a 20 year period. Histopathology reports and autopsies were reviewed. Information on predisposing factors, symptoms, treatment and outcome was collected. All obtainable fungal blood stream isolates were subcultured and their susceptibility to common antifungals determined. RESULTS: In the 20 year period from 1980-1999, 19 episodes of invasive fungal infections were diagnosed in 18 infants and children in Iceland. Twelve episodes of fungemia occured in 11 children and the nationwide annual incidence increased from 0.28 to 1.90 cases/100,000/year (p=0.037) during the study period. Half of the children were premature infants. All patients had a central venous catheter at the time of blood culture and most had received intravenous antibiotics or corticosteroids. Candida albicans was the most commonly isolated species (nine of 12 episodes, 75%). In addition to patients with fungemia, three children were diagnosed with disseminated fungal infection by histology or autopsy. Two cases of fungal meningitis, without fungemia, were identified. Furthermore, two children had invasive infections with Aspergillus fumigatus and both patients survived. Three children (3/16; 19%) with invasive Candida-infections died. CONCLUSIONS: In this study of invasive fungal infections among Icelandic children we demonstrate that the incidence of fungemia has risen significantly in the past 20 years. Diagnosis of invasive fungal infections can be complicated and negative blood cultures do not exclude disseminated infection. Given the high attributable mortality, timely diagnosis and aggressive treatment is extremely important.

Characteristics and dynamics of bacterial populations during postantibiotic effect determined by flow cytometry.

Changes in bacterial ultrastructure after antibiotic exposure and during the postantibiotic effect (PAE) have been demonstrated by electron microscopy (EM). However, EM is qualitative and subject to individual interpretation. In contrast, flow cytometry gives qualitative and quantitative information. The sizes and nucleic acid contents of Escherichia coli and Pseudomonas aeruginosa were studied during antimicrobial exposure as well as during the PAE period by staining the organisms with propidium iodide and analyzing them with flow cytometry and fluorescence microscopy. The effects of ampicillin, ceftriaxone, ciprofloxacin, gentamicin, and rifampin were studied for E. coli, whereas for P. aeruginosa imipenem and ciprofloxacin were investigated. After exposure of E. coli to ampicillin, ceftriaxone, and ciprofloxacin, filamentous organisms were observed by fluorescence microscopy. These changes in morphology were reflected by increased forward light scatter (FSC) and nucleic acid content as measured by flow cytometry. For the beta-lactams the extent of filamentation increased in a dose-dependent manner after drug removal, resulting in formation of distinct subpopulations of bacteria. These changes peaked at 20 to 35 min, and bacteria returned to normal after 90 min after drug removal. In contrast, the subpopulations induced by ciprofloxacin did not return to normal until > 180 min after the end of the classically defined PAE. Rifampin resulted in formation of small organisms with low FSC, whereas no distinctive characteristics were noted after gentamicin exposure. For P. aeruginosa an identifiable subpopulation of large globoid cells and increased nucleic acid content was detected after exposure to imipenem. These changes persisted past the PAE, as defined by viability counting. Swollen organisms with increased FSC were detected after ciprofloxacin exposure, even persisting during bacterial growth. In summary, for beta-lactam antibiotics and ciprofloxacin, the PAE is characterized by dynamic formation of enlarged cell populations of increased nucleic acid content, whereas rifampin induces a decrease in size and nucleic acid content in the organisms. Flow cytometry is an ideal method for future studies of bacterial phenotypic characteristics during the PAE.

Acute bacterial meningitis in adults. A 20-year overview.

BACKGROUND: Most clinical overviews of acute bacterial meningitis have either focused on children or all age groups combined, although the disease poses serious problems in the adult population. OBJECTIVE: To study the clinical and microbiological features of adult bacterial meningitis in Iceland, as a representative of the average European or North American community. PATIENTS AND METHODS: Data on a total of 132 cases in 127 patients (age, > or = 16 years) who were diagnosed as having acute bacterial meningitis in Iceland during the years 1975 to 1994 were collected from patient and laboratory records. Complete hospital records were found for 119 of the 132 cases identified. RESULTS: The annual incidence was 1.7/100,000 to 7.2/ 100,000 inhabitants (mean, 3.8/100,000). The most common causative organisms were Neisseria meningitidis (56%), Streptococcus pneumoniae (20%), Listeria monocytogenes (6%), and Haemophilus influenzae (5%). Neisseria meningitidis caused 93% of the infections in the 16- to 20-year-old age group, but it caused only 25% of the infections in patients aged 45 years or older. Listeria monocytogenes caused 14% of these cases. Cases of nosocomial and recurrent meningitis were rare. A significant underlying illness or condition was present in 39% of the patients. The mean mortality was 19.7%, and it did not change during the study period. CONCLUSIONS: In a study that involved all adult patients with bacterial meningitis in a single country for 2 decades, meningococci and pneumococci were the most frequent causative agents. However, meningococci were responsible for only one fourth of the cases among adult patients aged 45 years or older, most of these cases were caused by pneumococci and Listeria. Despite modern medical developments, approximately 20% of adult patients with bacterial meningitis died.

[Nosocomial infections in the Intensive Care Unit at Landspitalinn.].

OBJECTIVE: To determine the nosocomial infection rate, pathogens, colonisation and hospital mortality in the Intensive Care Unit (ICU) at Landspitalinn, which is a ten bed, general medical-surgical ICU. METHODS: Patients admitted for more than 48 hours were included. Surveillance- cultures were performed on admission and thereafter three times a week (tracheal aspirate, oropharyngeal swab, gastric aspirate, urine and other specimens as indicated). ICU infections were defined by the criteria of CDC, USA. In the first 12 months 140 patients met the inclusion criteria at 150 admissions. The study is ongoing. RESULTS: Eighty-seven ICU-acquired infections were diagnosed in 48 of the 150 admissions (32%), the mean age was 58 years (0-87) and 60% were males. The most common infections were: UTI 27 (31%), pneumonia 18 (21%), septicemia 15 (17%), wound infections eight (9%) and tracheitis seven (8%). Etiologic agents of the 87 infections were E. coli (15), Klebsiella sp. (7) and other Enterobacteriacae (9), Enterococcus sp. (12), Candida sp. (12), S. epidermidis (7), P. aeruginosa (7) and other/unknown pathogens (18). Infected patients stayed for a mean of 15.0 days and uninfected patients 4.2 days (p<0.05). Every patient staying for more than three weeks had at least one infection. The mean age of infected patients was 63 years and of uninfected patients 56 years (p<0.05). Neither APACHE-II nor TISS score on admission differed significantly between the infected and uninfected groups. Mortality in the ICU was 10.4% (5/48) in the infected group and 19.6% (20/102) in the uninfected group (p=0.24). CONCLUSION: Nosocomial infections in patients admitted to the ICU were common and associated with extended stay. Most of the infections were caused by Gram-negative bacilli.

Different patterns of bacterial DNA synthesis during postantibiotic effect.

Studies on bacterial metabolism during the postantibiotic effect (PAE) period are limited but might provide insight into the nature of the PAE. We evaluated the rate of DNA synthesis in bacteria during the PAE period after a 1-h exposure of organisms in the logarithmic growth phase to various antibiotics. Staphylococcus aureus ATCC 25923 was exposed to vancomycin, dicloxacillin, rifampin, and ciprofloxacin; Escherichia coli ATCC 25922 was exposed to gentamicin, tobramycin, rifampin, imipenem, and ciprofloxacin; and Pseudomonas aeruginosa ATCC 25783 was exposed to imipenem, tobramycin, and ciprofloxacin. DNA synthesis was determined by measuring the rate of [3H]thymidine incorporation in S. aureus and E. coli and [3H]adenine incorporation in P. aeruginosa. DNA synthesis in S. aureus was suppressed during the PAE phase with vancomycin, dicloxacillin, and rifampin, it was suppressed in E. coli with rifampin, and it was suppressed in P. aeruginosa after exposure to tobramycin. Conversely, DNA synthesis was relatively enhanced in the gram-negative bacilli after exposure to imipenem and in all three species after exposure to ciprofloxacin. However, DNA synthesis in E. coli was only minimally affected after exposure to tobramycin and gentamicin. The differences in DNA synthesis observed after exposure to various antimicrobial agents suggest multiple mechanisms for the PAE.

The in-vitro effect of temperature on MICs, bactericidal rates and postantibiotic effects in Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Varying temperatures (35.5 degrees C, 38.5 degrees C, 41 degrees C) only minimally affected growth rates in vitro of Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, as well as bactericidal rates and postantibiotic effects of several antibiotics. However, MICs were reduced at least four-fold by increasing temperature in 25% of the drug-organism combinations tested.

[Acute bacterial meningitis in adults, a 20 year overview.].

INTRODUCTION: Although acute bacterial meningitis is most common among children, the disease nevertheless poses serious problems in the adult population. However, most clinical overviews of the disease have either focused on children or all age groups combined. SUBJECTS AND METHODS: Information on all patients 5=16 years of age diagnosed in Iceland during the years 1975-1994 was collected from patient records from 10 hospitals and the records of the Dept. of Microbiology at the University Hospital which processes all bacterial isolates from the CSF identified in the country. RESULTS: One hundred thirty six patients were identified, but complete records were found for 123 patients. Yearly incidence ranged from 1.7-7.2/100,000 inhabitants with a mean of 3.8/100,000. The most common causative organisms were Neisseria meningitidis (54%), Streptococcus pneumoniae (20%), Listeria monocytogenes (6%) and Haemophilus influenzae (5%). The relative incidence of N. meningitidis was dependent on age, the organism caused 93% of infections in the 16-20 year age group, whereas only 25% of infections in subjects 3=45 years of age were due to meningococci. On the other hand, the relative incidence of S. pneumoniae did increase from 2% in the younger age group to 37% in the older subjects. L. monocytogenes caused 14% of cases among patients 3=45 years of age. The mean mortality was 19.1% and did not change significantly during the study period. A significant underlying illness or condition was present in 39% of the patients. During the first third of the study period penicillin or ampicillin alone or in combination with chloramphenicol were used as initial empiric therapy in 76% of cases, wheras during the last third of the period these agents were used initially in 24% of patients. The third generation cephalosporins either alone or in combination were instead employed for empiric treatment in almost two-thirds of the patients. CONCLUSIONS: Meningococci were the most common cause of bacterial meningitis in adults in Iceland during the study period, albeit age dependent, and causing only a fourth of infections in patients 3=45 years of age. Mortality did not change during the period. The third generation cephalosporins are now the most commonly used agents for empiric therapy.

Age specific prevalence of antibodies against Chlamydia pneumoniae in Iceland.

Chlamydia pneumoniae is a newly recognized common cause of respiratory tract infections. The aim of this study was to examine its prevalence in Iceland. The study was based on 1020 serum samples from individuals 0-99 years old. The samples were divided into 10-year age groups. IgG and IgM antibodies were determined with microimmunofluorescence assay. An IgG titer > or = 32 and IgM titer > or = 16 were considered positive. The prevalence of positive IgG titer in the study population was 53 +/- 16% (mean +/- SD, age group range 14-66%). Neither seasonal nor gender-based difference in IgG antibody prevalence was demonstrated. It was lowest in the youngest group, 0-9 years old (p < 0.001), but rose linearly to age 70 (p < 0.005). 34 samples were IgM positive on initial testing; most from the older age groups. 12 were rheumatoid factor positive as well. After treatment with caprine antihuman IgG antibodies all became negative. The prevalence of C. pneumoniae infections is high in Iceland according to these results and similar to that in neighbouring countries. The presence of IgM rheumatoid factor may cause false positive tests for pathogen-specific IgM by immune complex binding with pathogen-specific IgG, thereby requiring its removal before testing.

Ultrastructural alterations of bacteria during the postantibiotic effect.

Ultrastructural alterations of Staphylococcus aureus and Pseudomonas aeruginosa were examined during the postantibiotic effect (PAE) with transmission electron microscopy. After exposure to dicloxacillin the staphylococci were characterized by an increase in the number of crosswalls, rifampin produced thickening of the cell wall, but only minimal changes were induced by gentamicin. Intracellular electrondense aggregates were observed in P. aeruginosa after exposure to imipenem, tobramycin and ciprofloxacin, and imipenem caused globoid cell formations. These alterations were not uniform in every organism, but they correlated well with the duration of the PAE determined by viable counts.

The post-antibiotic effect of antimicrobial combinations in a neutropenic murine thigh infection model.

The post-antibiotic effect (PAE) may allow for more widely spaced dosing of antibiotics than is currently employed without loss of efficacy. Antimicrobial combinations are widely used in clinical medicine. However, dosing schedules are usually based on pharmacological profiles of the drugs used alone. Previously we have demonstrated significant prolongation of the PAE induced by antimicrobial combinations in vitro as compared to PAEs induced by the agents alone. We examined this issue further in vivo in a neutropenic mouse thigh infection model, by exposing Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae to several antimicrobials, either singly or in combination. The PAE in vivo was defined as the difference in time needed for the organisms in the treated animals to grow 1 log10 as compared with controls after serum drug concentrations had fallen below the MIC. Drug concentrations exceeded the MIC for 1.2-3.2 h, but bactericidal activity occurred mainly during the first hour. When the agents were used singly a negative PAE was produced by ceftazidime against P. aeruginosa, a PAE of approximately 0 h by imipenem against E. coli and K. pneumoniae, a PAE of 2-4 h by cefazolin against S. aureus, gentamicin against E. coli and K. pneumoniae, and imipenem and tobramycin against P. aeruginosa, and a PAE of 6-7 h by gentamicin against S. aureus and rifampicin against P. aeruginosa. The beta-lactam/aminoglycoside combinations when used against S. aureus and P. aeruginosa prolonged the PAE by 1.0-3.3 h, compared with the longer of the individual drug PAEs, but no prolongation was observed against E. coli and K. pneumoniae. Ceftazidime reduced the PAE when used with tobramycin against P. aeruginosa. The long PAE of rifampicin against P. aeruginosa was 'carried over' to the combination, thus prolonging the growth suppression achieved by imipenem and tobramycin alone or in combination by 5.5-8.0 h. This effect on the PAE was additive only, and synergy was not observed. In conclusion, a potentially significant prolongation of the PAE by combination of drugs was observed in vivo, but only if both (or all) agents induced a PAE when used alone. The impact of this observation needs to be examined further in studies involving multiple and different dosing regimens in an infection model.