Antibiotic susceptibility of blood culture isolates of Enterobacteriaceae. A Norwegian multicenter study.

From May to November 1997 each of six major hospitals throughout Norway collected 72 to 104 consecutive blood culture isolates of Enterobacteriaceae, altogether 563 isolates. Escherichia coli was the predominating organism (69%), followed by Klebsiella spp. (15%), Enterobacter spp. (6%), and Proteus mirabilis (4%). The susceptibility of the isolates to ampicillin, cefuroxime, ceftazidime, imipenem, tobramycin, and ciprofloxacin was determined by the E-test. 37% and 7% of the isolates were resistant to ampicillin and cefuroxime, respectively, and 1% were resistant to ceftazidime and tobramycin. Only one isolate of P. mirabilis was imipenem resistant. All isolates were susceptible to ciprofloxacin. The prevalence of ampicillin-resistant isolates at each hospital varied from 21 to 45%, and of cefuroxime-resistant isolates from 3 to 9%. The results were compared with those of a similar study performed in 1991-1992. No significant changes in the susceptibility to the various agents could be demonstrated. The high frequency of isolates resistant to ampicillin has clearly limited the usefulness of this agent in the treatment of septicemia and other serious infections caused by Enterobacteriaceae.

[Treatment of acute bacterial meningitis]. / Behandling av akutt bakteriell meningitt.

BACKGROUND: Acute bacterial meningitis requires immediate antimicrobial therapy. MATERIALS AND METHODS: Guidelines to antimicrobial treatment of children and adults with acute bacterial meningitis are presented. RESULTS: The most common agents causing acute bacterial meningitis are Streptococcus agalactiae in children less than one month of age, and Streptococcus pneumoniae and Neisseria meningitidis in individuals more than one month of age. If the causative bacterial agent is not known, children below one month of age should be given ampicillin and gentamicin, whereas older children and adults should be given benzylpenicillin in combination with either cefotaxime or ceftriaxone. We suggest treatment with specific antibiotic regimens in cases of known aetiology.

[Microorganisms strike back--infectious diseases during the last 50 years]. / Mikroorganismene slår tilbake--infeksjonssykdommene i de siste 50 år.

In the first half of the 20th century, improved living conditions, preventive measures, vaccines and antibiotics led to a marked reduction in morbidity and mortality from infectious diseases. It was predicted that the conquest of all infectious diseases was imminent. However, 50 years later, in 1999, they were still the major cause of disease worldwide, and caused nearly one third of all deaths (a total of 55.9 million). The eradication of smallpox in the 1970s and the approaching eradication of poliomyelitis represent major achievements. The prevalence of measles, pertussis and tetanus neonatorum is also markedly reduced, but still 1.5 million children in developing countries die each year because of lack of vaccines. Malaria and tuberculosis are re-emerging. Tuberculosis and HIV/AIDS are the diseases with known aetiology that cause most deaths, altogether 5 million each year. Respiratory and gastrointestinal infections cause 6.5 million deaths annually. Infections in the immunocompromised host have become a "trade mark" of today's advanced medicine. Almost every year, new diseases related to new micro-organisms are described; over the last 30 years, approximately 40 new diseases/micro-organisms have been diagnosed. Among the best known are HIV/AIDS, peptic ulcer caused by Helicobacter pylori, Legionnaires' disease, borreliosis (Lyme disease), hepatitis C, gastroenteritis caused by rotavirus, and Ebola haemorrhagic fever. Antimicrobial resistance development of micro-organisms has become one of the major health problems worldwide; a number of preventive measures are being introduced.

Eradication of non-typhoid salmonellae in acute enteritis after therapy with ofloxacin for 5 or 10 days.

Eradication of non-typhoid salmonellae was evaluated in a randomized, double-blinded study of 49 patients with acute enteritis after therapy with ofloxacin 400 mg once daily for 5 or 10 days. Early eradication of salmonellae was found in 57% of patients in the 5 day therapy group and in 74% of patients in the 10 day therapy group. This difference was larger among severely ill patients. Together with our previous study of ofloxacin therapy for 3 days or placebo, this shows that early eradication of non-typhoid salmonellae increases with duration of ofloxacin therapy without an increase in persistence of salmonellae in stools or development of resistant strains.

Spread of Staphylococcus aureus in hospitals: causes and prevention.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen in many hospitals worldwide. Even more alarming, MRSA strains that are vancomycin intermediate-susceptible are isolated with increasing frequency, making therapy for staphylococcal infections even more difficult and prevention more important than ever. Spread of S. aureus in hospitals and infection control measures are reviewed. The major sources of S. aureus in hospitals are septic lesions and carriage sites of patients and personnel. Carriage often precedes infection. The anterior nares are the most consistent carriage site, followed by the perineal area. Skin contamination and aerial dissemination vary markedly between carriers and are most pronounced for combined nasal and perineal carriers. The principal mode of transmission is via transiently contaminated hands of hospital personnel. Airborne transmission seems important in the acquisition of nasal carriage. Infection control strategies include screening and isolation of newly admitted patients suspected of carrying MRSA or S. aureus with intermediáte resistance to vancomycin, implementation of an infection control program to prevent transmission of resistant strains between patients and hospital personnel, and institution of a proper antibiotic policy to minimize antibiotic resistance development. MRSA carriers should be treated with intranasal antibiotics, e.g. mupirocin, and skin disinfectants to eliminate carriage. Education of hospital personnel is essential. Improved knowledge about the best ways to ensure favourable infection control practices is needed. Active intervention against the spread of MRSA is important.

[Pneumococcal vaccine]. / Pneumokokkvaksinen.

Streptococcus pneumoniae is a common cause of morbidity and mortality in children, immunodeficient individuals and elderly people. As antibiotic resistant strains become more prevalent, pneumococcal infections will become more difficult to manage. Pneumococcal vaccination is inexpensive, and serious side effects are rare. However, the efficacy and safety of the vaccine have been questioned, and the use of vaccination is limited. This article discusses factors to be considered when assessing the indications for pneumococcal vaccination. Immunisation together with a strict policy on the use of antibiotics are our most efficient means for preventing pneumococcal disease and spread of antibiotic resistant strains. Norwegian physicians are encouraged to use pneumococcal vaccine according to the present indications.

Vertebral osteomyelitis at a Norwegian university hospital 1987-97: clinical features, laboratory findings and outcome.

Altogether 40 patients aged 13-91 y (average 58 y) with vertebral osteomyelitis were treated at the Bergen University Hospital between July 1987 and June 1997. All patients presented with back pain, 33 (83%) had vertebral tenderness, and 26 (65%) patients were febrile. The duration of symptoms before diagnosis was < 3 weeks in 13 patients, and from 3 to 16 weeks in the remaining 27 patients. C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) were elevated in 39 and 38 patients, respectively. Staphylococcus aureus was the most frequent cause of osteomyelitis followed by Streptococcus spp., Escherichia coli and Mycobacterium tuberculosis. Magnetic resonance imaging was superior to other radiological methods and demonstrated changes consistent with osteomyelitis in all 23 patients examined with this method. 35 patients survived. 18/35 surviving patients had pareses and 17 underwent surgery with drainage of abscesses or laminectomy. All 35 patients made a good recovery and only 3 patients experienced permanent pareses. The diagnosis of vertebral osteomyelitis is easily missed, and treatment is often delayed, particularly in the elderly in whom signs of sepsis may not manifest. However, persisting localized pain and tenderness over the spine together with elevated CRP and ESR should prompt the physician to consider vertebral osteomyelitis. Fever and leukocytosis may support the diagnosis, but may not always be present.

Antibiotic susceptibility of blood culture isolates of Enterobacteriaceae from six Norwegian hospitals 1991-1992.

From August 1991 to February 1992, each of the six largest hospitals throughout Norway collected 84 to 107 consecutive blood culture isolates of Enterobacteriaceae, altogether 571 isolates. The distribution of various species and genera at the different hospitals was uniform; Escherichia coli being most prevalent (57-67%), followed by Klebsiella spp. (12-18%) and Proteus mirabilis (7-11%). Twenty-one and 4% of E. coli isolates were resistant to ampicillin and cefuroxime, respectively, and 11% of Klebsiella isolates were cefuroxime resistant. Five Enterobacter isolates and one Citrobacter isolate were resistant to ceftazidime, and one Salmonella isolate was resistant to imipenem. All isolates were susceptible to ciprofloxacin and tobramycin. These results were compared with the antibiotic consumption in each hospital region. Although hospitals in the regions with the highest consumption of ampicillin tended to have a higher percentage of isolates resistant to this agent, no significant differences were found. There was no significant difference between hospitals regarding prevalence of cefuroxime-resistant isolates.

Serum levels of adhesion molecules and cytokines in patients with acute leukaemia.

The cytokine network and the adhesion molecule system are intercellular signal pathways. The cytokine effects are modulated in vivo by soluble cytokine antagonists, whereas the cell to cell contact mediated by adhesion molecules and their ligands may be blocked by the soluble forms of the adhesion molecules. The cytokine network is important for proliferation and cytokine secretion by acute leukaemia blasts, and membrane-bound adhesion molecules are important for blast interactions with neighbouring cells of the in vivo microenvironment. Both these signal systems are operative during the period of cytopenia following intensive chemotherapy for acute leukaemia. In the present review, we discuss the influence of disease status, chemotherapy and complicating infections on serum levels of cytokines and soluble adhesion molecules in acute leukaemia patients. We have demonstrated increased serum levels of both cytokines and cytokine antagonists in acute leukaemia patients with complicating bacterial infections during chemotherapy-induced cytopenia. Serum levels of the selectin adhesion molecules were decreased during bacterial infections in leukopenic patients compared to healthy individuals. In contrast, the intercellular adhesion molecule-1 response and the cytokine/cytokine antagonist responses were qualitatively similar to responses seen in previously healthy individuals with serious bacterial infections.

Safety and efficacy of meropenem in patients with septicaemia: a randomised comparison with ceftazidime, alone or combined with amikacin.

Meropenem is a new broad spectrum carbapenem antibiotic which can be administered as monotherapy for serious infections. The efficacy and safety of meropenem was compared with that of ceftazidime (alone or in combination with amikacin) in 153 patients with septicaemia who were enrolled into identical, prospective, randomised studies. Forty-five patients with infections arising from the urinary or lower respiratory tracts were given either meropenem 500 mg or ceftazidime 250-1000 mg intravenously every 8 h; 108 patients with more serious infections were given meropenem 1 g or ceftazidime 2 g every 8 h +/- amikacin 15 mg/kg/day. Overall, 71 patients received meropenem, 47 ceftazidime and 35 ceftazidime plus amikacin. Comparable clinical response rates were achieved in the meropenem and ceftazidime/amikacin groups (92% vs 94% at the end of therapy respectively). Furthermore, a satisfactory bacteriological response was obtained in all evaluable patients. The most common pathogens isolated were Escherichia coli, Streptococcus pneumoniae and Pseudomonas aeruginosa. Relapse occurred in one patient in the ceftazidime/amikacin group, who had a mixed infection of E. coli and P. aeruginosa. There were no relapses in the meropenem group. Both treatments were well tolerated and only one patient had to withdraw from the trial because of an adverse effect (rash associated with ceftazidime). In conclusion, these data confirm that meropenem monotherapy is well tolerated and is as effective as ceftazidime (alone or combined with amikacin) in the empirical treatment of septicaemia. It should prove to be a useful addition to the drugs currently available for this life-threatening disease.

[Infection with group A Streptococcus]. / Infeksjoner med gruppe A-streptokokker.

In the last 8-10 years, the prevalence of severe group A streptococcus (GAS) infections such as bacteremia, erysipelas, necrotizing fasciitis and puerperal fever has increased significantly in industrialized countries. Shock, acute respiratory distress syndrome and multiorgan failure have been common features, and the attributable mortality has been as high as 30 per cent. The majority of infections have occurred in otherwise healthy adolescents and adults, and the GAS strains have been predominantly M types 1 and 3, which produce pyrogenic exotoxins, indicating an increased virulence of these strains. The article reports on the prevalence, pathogenesis, clinical features and treatment of severe GAS infections.

Neisserial porins inhibit human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but prime the neutrophils to increase their oxidative burst.

Porins are trimeric proteins that constitute water-filled pores that allow transmembrane diffusion of small solutes through the outer membrane layer of gram-negative bacteria. The porins are capable of inserting into the membranes of eucaryotic cells, and in the present study we have examined the in vitro effects on neutrophil functions of the following purified porins: meningococcal outer membrane protein classes 1 and 3 and gonococcal outer membrane protein 1B (P1B). The neisserial porins inhibited human neutrophil chemoattractant-induced actin polymerization and degranulation of both primary and secondary granules. The neutrophil expression of immunoglobulin G (IgG) Fc receptors II (Fc gamma RII; CDw32) and III (Fc gamma RIII; CD16), as well as the activation-dependent downregulation of Fc gamma RIII, were reduced by the meningococcal and gonococcal porins. The neisserial porins impaired the upregulation of complement receptors 1 (CD35) and 3 (CD11b) and inhibited the phagocytic capacity of neutrophils, as evaluated by the uptake of meningococci (strain 44/76) in the presence of patient serum containing known amounts of IgG against meningococcal porins. The porins also primed neutrophils to increase their intracellular hydrogen peroxide production in response to FMLP, whereas no such priming was observed if the neutrophil protein kinase C was stimulated directly with phorbol myristate acetate. The neisserial porins influenced neutrophil functions in a time- and concentration-dependent manner. The meningococcal class 1 outer membrane protein and the gonococcal P1B tended to alter neutrophil functions more than the meningococcal class 3 protein. Thus, the neisserial porins inhibited human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but primed the neutrophils to increase their oxidative burst. It remains to be determined whether these in vitro observations reflect mechanisms that may be of importance for the interaction between neutrophils and Neisseria species in vivo.

Bloodstream infections at a Norwegian university hospital, 1974-1979 and 1988-1989: changing etiology, clinical features, and outcome.

All episodes of bloodstream infection in patients admitted to a Norwegian university hospital in 1974-1979 and in 1988-1989 were analyzed; altogether, there were 1,447 episodes involving 1,286 patients, and 54.3% of all episodes were hospital-acquired. The incidence of bloodstream infection increased between the two periods studied from 4.26/1,000 admissions to 8.71/1,000. Crude mortality rates were 27.6% and 18.8% and attributable mortality rates were 12.3% and 6.9% in the first and second periods, respectively. Patients > 60 years of age accounted for more than half of the bloodstream infections; mortality in this group was significantly higher than that among younger patients (31.4% vs. 13.9%). The frequency of isolation of Enterobacteriaceae decreased from 48% in the first period to 34% in the second, while the rate of isolation of coagulase-negative staphylococci increased from 6.5% to 16.9%. The shift in etiology may be explained in part by the occurrence of significantly more bloodstream infections related to intravascular devices, endocarditis, and skin and wound infections and of significantly fewer episodes related to abdominal or genitourinary disease in the second than in the first period. Almost all isolates of Enterobacteriaceae were susceptible to newer cephalosporins and aminoglycosides. In 1974-1979, 96 (69.1%) of 139 patients with septic shock died; in 1988-1989, the figure was 35 (52.2%) of 67 patients (P = .019). Clinical factors predictive of an adverse outcome were septic shock (odds ratio for first/second period, 12.7/4.6), intensive care treatment (not significant/10.6), malignant disease (4.6/2.6), any underlying disease (4.2/not significant), diabetes mellitus (3.6/not significant), age of > 60 years (not significant/3.0), and pulmonary source of infection (not significant/2.8).

A longitudinal study of phagocyte function in HIV-infected patients.

OBJECTIVE: To study the influence of HIV infection on phagocyte function. To date, the results of phagocyte function studies in HIV-infected patients have been contradictory. This is the first longitudinal study of these functions in HIV infection. DESIGN: We followed 50 individuals with HIV infection for 2-51 months (mean, 28 months) and examined polymorphonuclear leukocyte (PMNL) and monocyte functions at intervals of 0.5-1 years. METHODS: PMNL random migration and chemotaxis were assessed using an under-agarose method, and PMNL and monocyte oxidative metabolism by chemiluminescence production during phagocytosis of opsonized zymosan. RESULTS: PMNL random migration and chemotaxis were impaired at entry into the study by 15 and 19%, respectively. After 3 years the reduction was 35 and 32%, respectively. The mean chemiluminescence production by PMNL was reduced by 6% at entry into the study. After 4 years a decrease of 18% was observed. The decrease in PMNL function was most marked in patients with lymphadenopathy syndrome or AIDS. No significant change in monocyte chemiluminescence production was detected at any time during the study. CONCLUSIONS: A distinct and progressive decrease of PMNL function occurs during HIV infection. This may contribute to increased susceptibility to opportunistic infections in HIV-infected patients. For monocytes, chemiluminescence production is not influenced by HIV infection.

Isoprinosine stimulates granulocyte chemiluminescence and inhibits monocyte chemiluminescence in vitro.

Isoprinosine may delay disease progression in human immunodeficiency virus infection, presumably through modulation of lymphocyte function. However, the influence of isoprinosine on phagocyte function is largely unknown. This study describes the effects of isoprinosine and azidothymidine on phagocyte chemiluminescence and migration. Incubation with isoprinosine concentrations of 250 micrograms/ml and above increased the chemiluminescence of granulocytes. Random migration of granulocytes was decreased at isoprinosine concentrations of 50 micrograms/ml and higher, but chemotaxis was not affected. Azidothymidine exerted no effect on the chemiluminescence or migration of granulocytes. For monocytes, luminol-enhanced chemiluminescence was reduced at isoprinosine concentrations of 250 micrograms/ml and above, whereas migration was not affected. These findings suggest that the immunomodulatory properties of isoprinosine may extend to phagocytic cells. This may be of significance in the treatment of immunodeficiency states.

Humoral immune response to class 1 outer membrane protein during the course of meningococcal disease.

We have determined the amounts of specific anti-class 1 outer membrane protein antibodies in sera from 25 patients during the course of systemic meningococcal disease, using purified class 1 protein as the sensitizing antigen in an enzyme-linked immunosorbent assay. The class 1 protein was obtained from a variant of strain 44/76 (B:15:P1.7,16) lacking class 3 and class 4 outer membrane proteins. Specific anti-class 1 (serosubtype P1.7,16) outer membrane protein immunoglobulin G (IgG) antibody levels increased significantly in 12 patients (12 of 25; 48%), regardless of the serotype of the infecting strain, indicating that the antibodies reacted in part with epitopes not determined by the monoclonal antibodies used for serotyping. Most patients had low levels of anti-class 1 IgG antibodies during the acute illness. The antibody levels peaked during the second week of disease and returned to near baseline levels in sera collected 6 weeks to 12 months after the onset of the disease. The majority of the specific anti-class 1 IgG antibodies bound to surface-exposed epitopes on whole bacteria and belonged to the IgG1 and IgG3 subclasses. Anti-class 1 IgA and IgM antibodies were not detected in any of the patient sera. Prior to disease, seven patients had been immunized with a meningococcal outer membrane vesicle vaccine developed from strain 44/76 (P1.7,16). None of these patients was infected with meningococcal strains containing class 1 protein homologous or partly homologous to that of the vaccine strain, indicating serosubtype-specific protection. The highest anti-class 1 IgG antibody peak levels were seen in immunized patients infected with strains of heterologous serotype, suggesting an anamnestic response. However, these patients were not protected from meningococcal disease after immunization.