The Norwegian experience with penicillin G plus an aminoglycoside as initial empiric therapy in febrile neutropenia; a review.

BACKGROUND: The occurrence of antibiotic resistance and the use of broad-spectrum antibiotics are relatively low in Norway. The national recommendation in febrile neutropenia (FN) is prompt initial therapy with penicillin G plus an aminoglycoside. We sought to evaluate the evidence behind this recommendation. METHODS: We did a literature search in Medline and EMBASE with search terms penicillin, aminoglycoside and febrile neutropenia. RESULTS: Seven Norwegian studies (six adult and one pediatric) conducted over the last 25 years were identified. They all conclude that penicillin G plus an aminoglycoside are effective and safe initial empiric antibiotic therapy in FN provided the regimen is modified if the clinical response is unsatisfactory. Overall 40-50% of the patients required only penicillin G and an aminoglycoside during their FN episode. The overall fatality rate was similar in the Norwegian and in international studies. CONCLUSION: Many countries use a broad-spectrum ß-lactam as initial therapy in FN. International experts are sceptic towards the Norwegian recommendations. We discuss the arguments for and against penicillin G plus an aminoglycoside in FN. The main arguments to continue the Norwegian treatment tradition are the satisfactory clinical results and the reason to believe that it contributes to the low levels of antibiotic resistance in Norway.

Community-acquired pneumonia (CAP) in children in Oslo, Norway.

AIM: To investigate the epidemiology and clinical characteristics of community acquired pneumonia (CAP) in children before the introduction of the 7-valent pneumococcal vaccine in the national vaccination programme. METHODS: For the period 21 May 2003 to 20 May 2005 hospitalization rates for pneumonia in children were obtained from retrospective studies of medical journals. Pneumonia was also studied prospectively in children less than sixteen years old referred to Ullevål University Hospital (Oslo) in the same time period. RESULTS: The overall observed hospitalization rate of pneumonia was 14.7/10 000 (95% CI: 12.2-17.1), for children under five it was 32.8/10 000 (95% CI: 26.8-38.8), and for children under two 42.1/10 000 (95% CI: 32.0-52.3). In the clinical study 123 children, of whom 59% (73) were boys, met the inclusion criteria and were enrolled. Only 2.4% (3) had pneumonia complicated with pleural effusion and in general few complications were observed. No patients required assisted ventilation, and none were transferred to the intensive care unit. Penicillin was effective as treatment for pneumonia. CONCLUSION: Pneumonia, seen in a paediatric department in Oslo, is a common but benign disease. Penicillin is effective as treatment for pneumonia in Norwegian children.

[Invasive pneumoccal disease in children in Oslo 1998-2004]. / Invasiv pneumokokkinfeksjon hos barn i Oslo 1998-2004.

BACKGROUND: Invasive pneumococcal disease (IPD) is an important cause of morbidity and mortality in Norwegian children. MATERIAL AND METHODS: This retrospective study included all children (under 16 years) with isolates of Streptococcus pneumoniae from a normally sterile site admitted to the Department of Paediatrics at Ullevaal University Hospital in the period 1998 to 2004. We studied the epidemiology, predisposing factors, clinical picture, antimicrobial resistance, outcome of IPD and the theoretical coverage of the 7-valent conjugate pneumococcal vaccine (PCV7) in these children. The isolates were tested for antimicrobial susceptibility, serogrouped and serotyped. RESULTS: 68 children were identified; 31 of them had one or more predisposing factors. Six children died, all of them had a predisposing factor. Six of the seven children who survived with sequelae were previously healthy. 67 of 68 isolates were fully susceptible to benzyl penicillin and 13 isolates showed intermediate susceptibility or resistance to erythromycin. Serogroups or serotypes were obtained in 66 children. 24 (36.8%) children fulfilled the criteria for PCV7. 35 (51.1%) children had serotypes covered by the vaccine. Only 12 (17.6%) fulfilled the criteria for PCV7 and had serotypes covered by it. Four of the six children who died had serotypes covered by PCV7. INTERPRETATION: Invasive pneumococcal disease is a serious condition in children and vaccination can prevent disease in many children.

Clinical symptoms and signs in sore throat patients with large colony variant beta-haemolytic streptococci groups C or G versus group A.

BACKGROUND: The role of large colony streptococci groups C or G as pathogen agents in sore throat has been questioned. AIM: To analyse clinical features of patients with large colony streptococci groups C or G compared with patients with group A streptococci (GAS) and with negative cultures. DESIGN OF STUDY: Prospective study of patients with sore throat. SETTING: Two Norwegian general practices in Stokke and Kongsberg communities with 6500 patients. METHOD: Frequency of clinical features in the three patient categories including the four Centor criteria (fever, anterior cervical lymphadenopathy, tonsillar exudates, and lack of cough), degree of pain on swallowing, pharyngeal rubor, C-reactive protein (CRP) values, patient age between 3 and 14 years, and duration of symptoms before seeing the doctor. A logistic regression analysis to find independent predictors was performed. RESULTS: Out of 306 patients with a sore throat, 244 were adults and 62 were children under 10 years old; 40% were men. One hundred and twenty-seven had GAS, 33 had streptococci groups C or G, and 146 had negative throat cultures. Forty-eight per cent of the GAS patients and 45% of the C or G patients met three or four of the Centor criteria. The logistic regression revealed that in patients with GAS considerable pain on swallowing, an age of 3-14 years and a duration of symptoms of < or =3 days or less were significantly associated with GAS infection in addition to the Centor criteria. The same results were found when all streptococci were analysed together, in addition elevated CRP was significant. In patients with streptococci group C or G an elevated CRP-value was significantly associated. CONCLUSION: Patients with tonsillitis caused by streptococcus groups C or G have, to a large extent, the same clinical picture as patients with GAS. Large colony streptococci groups C and G should be considered as throat pathogens in line with GAS.

Use of robotized DNA isolation and real-time PCR to quantify and identify close correlation between levels of Neisseria meningitidis DNA and lipopolysaccharides in plasma and cerebrospinal fluid from patients with systemic meningococcal disease.

The present study, using robotized DNA isolation and quantitative PCR based on the Neisseria meningitidis-specific capsular transport A gene, demonstrates the ease, rapidity, specificity, and sensitivity of quantifying neisserial DNA in plasma (n = 65) and cerebrospinal fluid (CSF) (n = 12) from patients with systemic meningococcal disease. We found a close correlation between the levels of neisserial DNA and lipopolysaccharides in plasma (r = 0.905) and in CSF (r = 0.964). The median concentration of neisserial DNA in plasma in 23 patients with persistent shock was 2 x 10(7) copies/ml, versus <10(3) copies/ml in 42 nonshock patients. Furthermore, quantitative PCR made possible estimates of the total number of meningococci in plasma, as opposed to conventional blood cultures, suggesting about 1,000 dead meningococci for every viable bacterium. Finally, with logistic regression analyses, neisserial DNA may predict a patient's disease severity and outcome at hospital admission. The number of meningococci in plasma and CSF appears to be the main determinant of the lipopolysaccharide levels, clinical presentation, and outcome.

Plasma interferon-gamma and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock.

OBJECTIVE: To analyze plasma interferon-gamma and interleukin-10 concentrations in patients with systemic meningococcal disease and patients with severe Gram-positive septic shock caused by Streptococcus pneumoniae or Staphylococcus aureus. To study the in vitro cytokine (interferon-gamma and interleukin-10) responses in a whole blood model boosted with heat-killed Neisseria meningitidis, S. pneumoniae, and S. aureus before and after treatment with recombinant interleukin-10 or recombinant interferon-gamma. DESIGN: Experimental study. SETTING: Laboratory. SUBJECTS: Plasma samples were collected from patients with systemic meningococcal disease (n = 66) and patients with severe Gram-positive septic shock caused by S. pneumoniae (n = 4) or S. aureus (n = 3). INTERVENTIONS: Whole blood was boosted with heat-killed N. meningitidis, S. pneumoniae, and S. aureus (1 x 106 colony forming units/mL), and plasmas were analyzed for interleukin-10 or interferon-gamma at 0, 5, 12, and 24 hrs. Furthermore, recombinant interleukin-10 or recombinant interferon-gamma was added before bacteria, and the effect on the secretion of interferon-gamma and interleukin-10, respectively, was analyzed after 24 hrs. MEASUREMENTS AND MAIN RESULTS: The median concentration of interferon-gamma was 15 pg/mL and of interleukin-10 was 10,269 pg/mL in patients with meningococcal septic shock (n = 24) compared with median interferon-gamma concentration of 3400 pg/mL and interleukin-10 concentration of 465 pg/mL in patients with severe Gram-positive shock (p =.001). Increased interferon-gamma concentrations were associated with case fatality (p =.011). In a whole blood model we demonstrated that 1 x 106 colony forming units/mL of N. meningitidis induced more interleukin-10 but less interferon-gamma than S. pneumoniae. S. aureus induced minimal secretion of both cytokines. Recombinant interleukin-10 efficiently down-regulated the secretion of interferon-gamma, and vice versa, as shown in a whole blood model. CONCLUSION: We speculate whether high concentrations of interleukin-10 contribute to the low concentrations of interferon-gamma in fulminant meningococcal septicemia. In addition, it appears as if interferon-gamma plays a minor role in the pathophysiology of meningococcal septic shock.

Which is the best method to trace group A streptococci in sore throat patients: culture or GAS antigen test?

OBJECTIVE: To compare an antigen detection test (GAS antigen test) with the results from combinations of two various bacteriological test media in general practice patients with sore throat. Furthermore to assess the diagnostic properties of the chosen GAS antigen test and to compare semi-quantitative results of this test with the bacterial load found in the throat culture. SETTING: Two Norwegian general practices in Stokke and Kongsberg communities. SUBJECTS: 306 patients with sore throat lasting less than 7 days; 244 were adults, 62 were children under 10 years old, mean age 23.9 years (SD 15.0), 40% were men. MAIN OUTCOME MEASURES: Results from GAS antigen test, and distribution of bacteriological findings in throat cultures, compared with the results of our GAS antigen test; semi-quantitative results of the GAS antigen test compared with the bacterial load by culture. RESULTS: In the primary culture 110 patients harboured group A streptococci (GAS) infection, while the second culture identified another 17, giving a total of 127 patients. Some 33 patients harboured large-colony groups C and G. The GAS antigen test used had a sensitivity of 97% and specificity of 95% regarding GAS when compared with the two cultures. We found a significant correlation between the bacterial loads by culture and the semi-quantitative results of the GAS antigen test. CONCLUSIONS: By using a second, different set of bacteriological media, we identified an additional 17 patients with GAS infections. This raises the question of validity of frequently used reference standards in studies related to streptococcal infections. Compared with the combined results of the two throat cultures, the GAS antigen test used showed high sensitivity and specificity. Semi-quantitative evaluations of the rapid immunological test may also be of clinical value.

Predictors for spread of clinical group A streptococcal tonsillitis within the household.

OBJECTIVE: The objectives of this study were to explore how frequently group A streptococci (GAS) were giving additional cases of clinical GAS tonsillitis within the households and to analyse predictors for such spread of GAS infection. SETTING: Two Norwegian general practice populations in Stokke and Kongsberg communities. PATIENTS: 110 households with at least one member with sore throat lasting less than 7 days, and GAS demonstrated in throat culture. Among the 110 index patients 51 (46%) were parents, 35 mothers and 16 fathers; 23 were children 6 years and younger, while 36 were children aged 7-15 years. MAIN OUTCOME MEASURES: Frequency of spread of clinical GAS infection to another household member within 4 weeks. Distribution of age and size of household in families with and without spread of GAS infection. RESULTS: In 30 (27%) households one or more new cases of GAS tonsillitis was found, adding 40 new infections. No spread of GAS disease was found in households with only adult members. A significantly higher proportion of spread was found in households with 4 or more members compared with households with fewer members, and low age of the index person. Short duration of symptoms before seeing a doctor was also associated with spread of GAS. In a logistic regression analysis carried out in the households with children, short duration of symptoms before diagnosis and treatment and low age of index person were significantly associated with spread of the infection. CONCLUSIONS: Even with standard penicillin treatment, GAS infection is frequently spread within households, and most frequently in households with children and many members.

Outer membrane vesicles from Neisseria meningitidis.

Flow cytometry was used to study the expression of leukocyte adhesion molecules CD11a, CD11b, CD11c, CD14, and CD62L (L-selectin) and production of reactive oxygen species (ROS) in an ex vivo human whole-blood system stimulated with lipopolysaccharide-containing outer membrane vesicles (LPS-OMV) from N. meningitidis. Results demonstrated a dose-dependent increase in surface expression of CD11a, CD11b, CD11c and CD14 in granulocytes and monocytes (maximal at 30-120 min) upon OMV-LPS challenge, whereas CD62L expression was heavily downregulated (maximal at 30-120 min). The OMV-associated LPS was almost as potent (on a weight basis) as purified LPS from E. coli in inducing adhesion molecule modulation but the response was delayed. Upon stimulation with OMV-LPS or E. coli-LPS, the production of intracellular ROS increased in both granulocytes and monocytes when dihydroethidium (DHE, mainly reflecting superoxide anion) was used as a probe, whereas peroxynitrite production monitored with dihydrorhodamine 123 (DHR) was not significantly changed. The OMV-mediated modulation of leukocyte adhesion molecule expression and increased ROS production may certainly lead to increased entrapment of leukocytes in the microcirculation and contribute to untoward inflammatory reactions as seen in systemic meningococcal disease.

Lactobacillus rhamnosus septicaemia in a patient with a graft in the inferior vena cava.

A case of septicaemia that repeatedly showed growth of Lactobacillus rhamnosus in blood cultures is reported. The patient improved after removal of a Goretex patch in the inferior vena cava that was the focus of the infection. Lactobacilli can, in certain settings, be the cause of clinically important infections.