Changing epidemiology of pediatric Staphylococcus aureus bacteremia in Denmark from 1971 through 2000.

BACKGROUND: Staphylococcus aureus is known to be a leading cause of bacteremia in childhood, and is associated with severe morbidity and increased mortality. To determine developments in incidence and mortality rates, as well as risk factors associated with outcome, we analyzed data from 1971 through 2000. METHODS: Nationwide registration of S. aureus bacteremia (SAB) among children and adolescents from birth to 20 years of age was performed. Data on age, sex, source of bacteremia, comorbidity and outcome were extracted from discharge records. Rates were population adjusted and risk factors for death were assessed by multivariate logistic regression analysis. RESULTS: During the 30-year study period, 2648 cases of SAB were reported. Incidence increased from 4.6 to 8.4 cases per 100,000 population and case-mortality rates decreased from 19.6% to 2.5% (P = 0.0001). Incidence in the infant age group (<1 year) were 10- to 17-fold greater compared with that in the other age strata and mortality rate was twice as high. Hospital-acquired infections dominated the infant group, accounting for 73.9%-91.0% versus 39.2%-50.5% in the other age groups. By multivariate analysis, pulmonary infection and endocarditis for all age groups, comorbidity for the older than 1 year, and hospital-acquired infections for the oldest group were independently associated with an increased risk of death. CONCLUSIONS: Mortality rates associated with SAB decreased significantly in the past 3 decades, possibly because of new and improved treatment modalities. However, incidence rates have increased significantly in the same period, underscoring that S. aureus remains an important invasive pathogen.

Staphylococcus aureus bacteremia.

Staphylococcus aureus bacteremia (SAB) is still associated with a high mortality, and knowledge on risk factors and the clinical and the therapeutic aspects of SAB is still limited. This thesis focuses on the clinical aspects of SAB and its metastatic infections. In a study of all patients with bacteremia in Copenhagen County October 1992 through April 1993 (study I) we emphasized previous findings, that S. aureus is one of the most frequent pathogens in bacteremia, and in a case control study also in Copenhagen County 1994-95 (study II) we demonstrated, that not only an inserted central venous catheter and nasal S. aureus carriage but also hyponatremia and anemia are important risk factors for hospital-acquired SAB (study II). Studies on the treatment of SAB have pointed out, that the eradication of a primary is important, but there are only limited clinical studies dealing with antibiotic treatment. By logistic regression analysis, we were able to demonstrate that focus eradication is essential, but also that treatment with dicloxacillin 1 g x 4 or 2 g x 3 are superior to 1 g x 3 (studie III), indicating that the time for serum concentration above the Minimal Inhibitory Concentration (MIC) for the bacteria plays a role in the outcome of SAB treatment. S. aureus osteomyelitis secondary to SAB is frequently observed. No other countries, however, have a centralized registration, which make it possible to evaluate a large number of these patients. Since 1960, The Staphylococcal Laboratory, Statens Serum Institut in Copenhagen, has registrated selected clinical informations from nearly all patients with positive blood cultures of S. aureus. Based on this registration, we were able to show an increased number of S. aureus osteomyelitis among older patients and a decreased number of S. aureus osteomyelitis of femur and tibia among younger infants in the period 1980-90 (study IV). By reviewing the records of a large number of patients with vertebral S. aureus osteomyelitis, we could evaluate important aspects in the diagnosis and treatment of these patients (study V). We illustrated, that symptoms and laboratory findings were relatively unspecific, and CT-scanning or bone scintigraphy were absolutely necessary for the diagnosis (study V). The relatively high number of patients in the study allowed us to evaluate different treatment regimens, and we found, that treatment with penicillinase-stable penicillins four grams daily for at least eight weeks was necessary (study V). S. aureus meningitis is relatively uncommon and most often a neurosurgical infection based on the presence of a catheter. Meningitis secondary to SAB is relatively rare. The nationwide registration on Statens Serum Institut enabled us to study a large number of patients with special emphasis on clinical, outcome and treatment (study VI). We found, that these patients often were older people with chronic underlying diseases, the infection developed as a community-acquired infection, and the patients also had an unknown focus of infection. Furthermore, these patients often had other secondary manifestations such as endocarditis or osteomyelitis and an extremely high mortality (study VI). Finally, I believe that our studies will contribute to reduce the incidence of SAB and improve the diagnosis and treatment of SAB in the future.