Multidrug-resistant tuberculosis in Norway: a nationwide study, 1995-2014.

SETTING: The management of multidrug-resistant tuberculosis (MDR-TB) is strictly regulated in Norway. However, nationwide studies of the epidemic are lacking. OBJECTIVE: To describe the MDR-TB epidemic in Norway over two decades. DESIGN: Retrospective analysis of data on MDR-TB cases in Norway, 1995-2014, obtained from the national registry, patient records and the reference laboratory, with genotyping and cluster analysis data. Data for non-MDR-TB cases were collected from the national registry. RESULTS: Of 4427 TB cases, 89 (2.0%) had MDR-TB, 7% of whom had extensively drug-resistant TB (XDR-TB) and 24% pre-XDR-TB. Of the 89 MDR-TB cases, 96% were immigrants, mainly from the Horn of Africa or the former Soviet Union (FSU); 37% had smear-positive TB; and 4% were human immunodeficiency virus co-infected. Of the 19% infected in Norway, the majority belonged to a Delhi/Central Asian lineage cluster in a local Somali community. Among the MDR-TB cases, smear-positive TB and FSU origin were independent risk factors for XDR/pre-XDR-TB. Treatment was successful in 66%; 17% were lost to follow-up, with illicit drug use and adolescence being independent risk factors. Forty-four per cent of patients treated with linezolid discontinued treatment due to adverse effects. CONCLUSION: MDR-TB is rare in Norway and is predominantly seen in immigrants from the Horn of Africa and FSU. Domestic transmission outside immigrant populations is minimal.

Low prevalence of positive interferon-gamma tests in HIV-positive long-term immigrants in Norway.

OBJECTIVE: To determine the prevalence and predictors of positive interferon-gamma release assays (IGRAs) and tuberculin skin tests (TSTs) in human immunodeficiency virus (HIV) infected patients in Norway, a low tuberculosis (TB) endemic country. DESIGN: Multicentre cross-sectional study of 298 HIV patients tested with QuantiFERON®-TB Gold In-Tube (QFT-GIT), T-SPOT®.TB (T-SPOT) and TST. RESULTS: A total of 77/298 (26%) QFT-GIT, 29/117 (25%) T-SPOT and 52/217 (24%) TSTs (≥ 5 mm) were positive. The median CD4 count was 427 cells/l. Three QFT-GIT results but no T-SPOT results were indeterminate. Of 52 TST-positive patients, 34 (65%) were QFT-GIT-positive (median interferon-gamma [IFN-] 4.38 international units [IU]/ml), compared to 16% of the TST-negative patients (median INF- 0.81 IU/ml, P < 0.001). Origin from a TB-endemic country, previous active TB and TB exposure were associated with a positive QFT-GIT (P 0.01). Patients from TB-endemic countries living in Norway for ≥ 10 years had lower odds of a positive QFT-GIT (12%; OR 0.17, 95%CI 0.060.53, P 0.002) than patients with 03 years' residence (49%). CONCLUSION: The prevalence of positive IGRAs in HIV-infected patients was high in this low TB endemic setting. Lower QFT-GIT positivity in long-term residents from TB-endemic countries may reflect a waning of TB-specific immune responses.

p24 antigen detection on dried blood spots is a feasible and reliable test for infant HIV infection in rural Tanzania.

The difficulty of diagnosing HIV in infants is a major obstacle to early antiretroviral therapy (ART) in resource-limited settings. As serological tests are unreliable during the first 18 months of life, and the cost and complexity of polymerase chain reaction (PCR)-based assays limit their access in resource-limited settings, p24 antigen detection has emerged as an alternative diagnostic tool. In this study, the performance of an ultrasensitive p24 antigen assay on dried blood spots was evaluated under field conditions in rural Tanzania. Specimens were stored and shipped at tropical room temperature, and analysed within six weeks. In total, 27 consecutive children aged <18 months and exposed to vertical HIV transmission were enrolled. Overall sensitivity and specificity was 100% (95% confidence interval [CI], 47.8-100) and 95.5% (95% CI, 77.2-99.9), respectively. Our findings suggest that detection of p24 antigen on dried blood spots can be a reliable and feasible diagnostic tool for infant HIV infection in rural resource-limited settings.

Depletion of mitochondrial DNA copies/cell in peripheral blood mononuclear cells in HIV-1-infected treatment-naïve patients.

OBJECTIVES: Mitochondrial toxicity is believed to be the main reason for adverse effects related to nucleoside reverse transcriptase inhibitors (NRTIs). The aim of the present study was to compare mitochondrial toxicity in NRTI-treated HIV-positive patients, HIV-positive treatment-naïve patients and HIV-negative controls by comparing mitochondrial DNA (mtDNA) copies/cell in peripheral blood mononuclear cells (PBMCs) and lactate/pyruvate (L/P) ratios in the different groups. METHODS: We enrolled 60 participants in the study: 31 patients on combined antiretroviral therapy (CART), 14 HIV-positive treatment-naive patients and 15 HIV-negative controls. mtDNA (copies/cell) in peripheral blood was analysed using quantitative real-time polymerase chain reaction (PCR). Standard curves and serial dilutions of plasmid-cloned mitochondrion and retinoblastoma (RB1) PCR products with known concentrations were generated to estimate the mtDNA and nuclear DNA (nDNA) copy numbers in each sample. The L/P ratio was enzymatically and spectrophotometrically analysed in samples from individuals in a fasted, non-exercise state. Results The median mtDNA copy number was 63 copies/cell (interquartile range 33-94) in HIV-positive patients and 153 (132-283) in HIV-negative controls (P<0.001). No significant difference was seen between the HIV-positive NRTI-exposed patients and the HIV-positive treatment-naive patients. Current use of didanosine was negatively correlated with depletion of mtDNA (r=-0.36, P=0.046). HIV-positive patients also had a higher L/P ratio compared with HIV-negative controls (P=0.004). CONCLUSIONS: The number of mtDNA copies/cell in PBMCs was depleted in HIV-positive treatment-naive patients as well as in HIV-positive NRTI-exposed patients. HIV-positive patients also had a higher L/P ratio compared with HIV-negative controls, which supports this conclusion. The study suggests that neither mtDNA in PBMCs nor L/P ratio is a good marker of NRTI-associated mitochondrial toxicity.

Lipoatrophic men 44 months after the diagnosis of lipoatrophy are less lipoatrophic but more hypertensive.

OBJECTIVES: To identify clinical factors associated with HIV-associated lipoatrophy and to evaluate body composition changes, blood pressure and lipid levels in lipoatrophic subjects 3-4 years after the atrophy diagnosis. METHODS: Clinical signs of lipoatrophy were assessed in 308 ambulant HIV-positive patients in 2000-2001. Possible clinical risk factors, such as age, gender, race, wasting, duration of HIV infection, presence or absence of AIDS diagnosis, viral load and CD4 count, and detailed information about drug treatment were analysed and explored in a multivariate model. Lipoatrophic white males with triceps skin fold <10 mm were re-examined after 44 months. Signs of lipoatrophy and associated factors, blood pressure, lipid levels, diet and level of exercise at first and second visits were compared. RESULTS: In the multivariate analysis, significant clinical risk factors for lipoatrophy were weight loss >7 kg compared to normal weight [odds ratio (OR) 3.76; 95% confidence interval (CI) 1.80-7.82; P<0.001], current and/or previous use of stavudine (OR 3.72; 95% CI 1.57-8.83; P=0.003) and duration of HIV infection >80 months (OR 2.28; 95% CI 1.13-4.59; P=0.021). Forty of 47 lipoatrophic white males with skin fold < 10 mm were available for re-examination. Of these, 15 (38%) no longer fulfilled the atrophy diagnosis (P<0.001). The prevalence of arm atrophy fell from 63 to 28% (P=0.001) and facial atrophy from 55 to 43% (P=0.23). Use of stavudine for < 36 months was significantly associated with lipoatrophy reversal (OR 5.00; 95% CI 1.15-21.80; P=0.032), but weight gain and increased CD4 count were not. Prevalence of hypertension increased from 28 to 50% (P=0.035), mean systolic blood pressure from 130+/-14 to 136+/-19 mmHg (P=0.021) and diastolic blood pressure from 82+/-10 to 87+/-12 mmHg (P<0.001). In spite of increased use of lipid-lowering drugs (from two to nine patients), levels of total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were unchanged. CONCLUSIONS: In this study, we found that weight loss >7 kg, use of stavudine and long duration of HIV infection were significant risk factors for clinical lipoatrophy. Clinical lipoatrophy was partly reversible, and <36 months on stavudine was significantly associated with atrophy reversal. The prevalence of hypertension and the yearly increase of mean blood pressure were disturbingly high in these patients. However, the number of patients in this study was limited, and prospective studies in larger cohorts are required to confirm these findings.

An algorithm-based genotypic resistance score is associated with clinical outcome in HIV-1-infected adults on antiretroviral therapy.

OBJECTIVES: The aim of this study was to evaluate the association between genotypic drug resistance and the occurrence of HIV-related diseases and death in HIV-1-infected adults on antiretroviral therapy. METHODS: We performed an observational study on patients from an out-patient clinic in a university hospital. Genotypic drug resistance analysis after virological treatment failure was performed in 141 patients receiving two or more antiretroviral drugs. All patients had follow up of at least 6 months after the resistance test. An algorithm was developed to estimate the level of genotypic drug resistance and to assign an actual resistance score (ARS) for the drugs prescribed to each patient. The patient population was divided into quartiles according to patients' ARS values. Our endpoint was the risk of developing an HIV-related disease [Centers for Disease Control and Prevention (CDC) category B or C] during the period starting 6 months prior to and ending 6 months after the genotypic resistance test, or death during the 6 months following the resistance test. RESULTS: There was a significant association between the level of resistance to the drugs prescribed (ARS) and our clinical endpoint: the odds ratio for an endpoint (with 95% confidence interval) was 3.20 (1.28-7.99), adjusted for CD4 cell count and HIV RNA, in patients in the highest ARS quartile compared with patients in the other three quartiles. CONCLUSIONS: Our study indicates that patients with high-level genotypic drug resistance are at increased risk of developing an HIV-related disease. This association could not be explained by differences in CD4 cell count or HIV RNA levels.

Elevated Framingham risk score in HIV-positive patients on highly active antiretroviral therapy: results from a Norwegian study of 721 subjects.

Highly active antiretroviral therapy (HAART) may induce dyslipidemia and thus increase the risk of future cardiovascular heart disease (CHD). In this cross-sectional study performed in 2000-2001, the prevalence of a Framingham CHD risk score of >20% in HIV-positive individuals treated or not treated with HAART was compared with that in age- and gender-matched controls. The study included 721 subjects: 219 HIV-positive individuals on HAART, 64 HIV-positive, HAART-naïve individuals, and 438 age- and gender-matched controls randomly selected from a simultaneous health survey. The prevalence of a 10-year estimated CHD risk of >20% was 11.9% in patients on HAART compared to 5.3% in controls ( P=0.004). The main contributors to the increased CHD risk in patients on HAART were increased prevalence of daily smoking (54.5% vs 30.1%; P<0.001), total cholesterol of >6.2 mmol/l (36.1% vs 21.7%; P<0.001), and HDL cholesterol of < 0.9 mmol/l (20.9% vs 8.0%; P<0.001). In HAART-naïve patients, the prevalence of a 10-year estimated CHD risk of >20% was 6.3% ( P=0.25 vs HAART patients, P=0.76 vs controls), the prevalence of daily smoking was 56.3% ( P=0.89 vs HAART patients, P<0.001 vs controls), the prevalence of total cholesterol >6.2 mmol/l was 9.4% ( P<0.001 vs HAART patients, P=0.019 vs controls), and the prevalence of HDL cholesterol of <0.9 mmol/l was 30.9% ( P=0.16 vs HAART patients, P<0.001 vs controls). The results show that, compared to controls, twice as many patients on HAART have an estimated 10-year CHD risk above 20%. These patients are candidates for intensive interventions. HAART patients should be encouraged to permanently stop smoking, make healthy food choices, and increase physical activity. In patients with elevated lipid levels, a change in the HAART regimen or treatment with lipid-lowering drugs should be considered.

Prevalence of hypertension in HIV-positive patients on highly active retroviral therapy (HAART) compared with HAART-naïve and HIV-negative controls: results from a Norwegian study of 721 patients.

Highly active antiretroviral therapy (HAART) may induce dyslipidemia, insulin resistance and body fat distribution similar to that seen in the metabolic syndrome. Hypertension is often a part of the classic metabolic syndrome, but few studies are published about hypertension in HIV-positive patients on HAART. The aim of this study was to compare the prevalence of hypertension in HIV-positive patients on HAART with that in HIV-positive/HAART-naïve patients and HIV-negative controls. The cross-sectional study included 283 unselected HIV-positive ambulatory patients, 219 who were on HAART and 64 who were HAART-naïve. Age- and gender-matched controls (n=438) were randomly selected from a simultaneous health survey of the general population. The prevalence of hypertension was 21% in patients on HAART, 13% in HAART-naïve patients (P=0.20), and 24% in HIV-negative controls (P=0.28). Among several possible risk factors for hypertension, only body mass index (BMI) was found to be a confounder. BMI was similar in HAART-treated and HAART-naïve patients but elevated in controls compared to HAART-treated patients. After adjustment for BMI, the prevalence of hypertension in HIV-negative controls was slightly lower than that in patients on HAART (P=0.29). The results demonstrated a prevalence of hypertension in patients on HAART similar to that in HIV-negative controls. The prevalence of hypertension was somewhat higher in patients on HAART compared to HAART-naïve patients, but the difference was not statistically significant. Considering the marked drop in mortality following antiretroviral therapy, we conclude that the possible influence of HAART on the prevalence of hypertension appears to be a minor problem.

Early psychomotor slowing predicts the development of HIV dementia and autopsy-verified HIV encephalitis.

OBJECTIVES- To ask if slowed motor speed predicts later human immunodeficiency virus (HIV) dementia and HIV encephalitis. METHODS- In 100 deceased acquired immunodeficiency syndrome (AIDS) patients prior results from repeated testing of the movement reaction time test were correlated with later clinical signs of HIV dementia and with neuropathological signs of HIV encephalitis. Autopsy was performed in 72 patients. RESULTS- Movement reaction time 1-2 years prior to death, or at the time of clinical AIDS diagnosis predicted both development of HIV dementia (P<0.05) and HIV encephalitis at autopsy (P<0.01). CONCLUSION- Testing for early psychomotor slowing may be used to identify patients at risk of HIV dementia and HIV encephalitis.

Do HIV-seropositive patients become colonised with drug-resistant microorganisms?

The aim of the present study was to investigate whether HIV-infected patients, a group that is supposedly at risk for infection with antibiotic-resistant microbes, really does so, and to assess possible risk factors for acquiring these organisms. During the period from January 1998 to July 1999, samples of normal flora were obtained from 107 HIV-infected patients attending an outpatient clinic in Oslo, Norway. The samples were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, coagulase-negative staphylococci and Candida spp., and the resulting isolates were tested for antimicrobial susceptibility. The patients studied represented all stages of HIV infection, from recently infected to severely immunocompromised. Samples were taken at one, two or three time-points to determine whether antimicrobial resistance in colonising microorganisms increases over time. Antimicrobial resistance was linked primarily to antimicrobial prophylaxis, but it did not increase during the observation period. The level of a patient's immunodeficiency and the consequently intensified medical care was also of some importance. Even though about 50% of the patients were receiving antimicrobial agents at the time of sampling, the level of resistance found in these patients was very similar to that found in other patient groups in Norway; except for Candida albicans isolates, which were less susceptible to fluconazole. Overall, antimicrobial resistance was uncommon in the HIV-seropositive patients studied, a finding that is probably related to the overall low prevalence of antimicrobial resistance in the general population in Norway.

Dementia in AIDS patients in Oslo; the role of HIV encephalitis and CMV encephalitis.

In a well-defined population of adult AIDS patients from Oslo, we studied the correlation between clinical dementia and autopsy results. The study included 91% of all adult AIDS patients from Oslo who died between 1983 and 1996. The autopsy rate was 73% (167/229). Twenty-three percent of patients had definite dementia and 24% possible dementia. In more than half of the patients with definite dementia multinucleated giant cells were present in the brain tissue, suggesting that the dementia was due to HIV encephalitis. Diffuse damage of white matter also showed a significant association with clinical dementia. When found alone it tended to occur in symptomatic patients with a short survival time from onset of dementia until death. This indicates that diffuse damage of white matter may be an early stage of HIV encephalitis. CMV encephalitis was found in 28 cases (17%). Of these, 20 were classified as definitely or possibly demented. In 14 of these 20 cases we detected no multinucleated giant cells, suggesting that CMV caused or contributed to the dementia. Multiple logistic regression supported an association between CMV and conditions clinically classified as HIV dementia. We conclude that HIV encephalitis is the major cause of dementia in AIDS patients, but that CMV encephalitis as a cause of dementia has been underestimated.

Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.

OBJECTIVE: To compare the clinical response among patients who initiate protease inhibitor therapies with different virological potency. DESIGN: We analysed patients who started indinavir, ritonavir or saquinavir hard gel capsule (hgc) as part of at least triple therapy during prospective follow-up within the EuroSIDA study. METHODS: Changes in plasma viral load (pVL) and CD4 cell count from baseline were compared between treatment groups. Time to new AIDS-defining events and death were compared in Kaplan--Meier models, and Cox models were established to further assess differences in clinical progression (new AIDS/death). Adjustment was made for differences in baseline parameters, in particular pVL, CD4 cell count, and region of Europe. RESULTS: A total of 2708 patients (median follow-up: 30 months) were included, of which 556 started ritonavir (21%), 1342 indinavir (50%), and 810 saquinavir hgc (30%). The three groups were fairly evenly balanced at baseline regarding CD4 count, previous diagnosis of AIDS and pVL, After 12 months, the median changes in CD4 cell count were 90, 96 and 74 x 10(6) cells/l, respectively;P < 0.001, the proportions of patients with pVL < 500 copies/ml were 47, 54 and 41%; P < 0.001, and the proportions with clinical progression were 11.9, 9.2 and 11.9%, respectively; P = 0.20 (log-rank test). In multivariate models the relative risk of clinical progression for indinavir compared with saquinavir hgc was: 0.77 (0.60--0.99); P = 0.043, and for ritonavir 0.83 (0.62--1.11); P = 0.20. CONCLUSIONS: Saquinavir hgc was associated with an inferior long-term clinical response relative to indinavir, which was consistent with the observed differences in virological and immunological responses.

Influence of age on CD4 cell recovery in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy: evidence from the EuroSIDA study.

Influence of age on the CD4 cell response to highly active antiretroviral therapy (HAART) was examined in 1956 patients (median age, 37.2 years) in the EuroSIDA study. Median initial CD4 cell count was 192x106 cells/L, follow-up was 31 months, and time to maximum CD4 cell response was 20 months. Age groups were not different for baseline CD4 cell count, baseline human immunodeficiency virus RNA load, or treatment history. CD4 cell increase, stratified by age quartiles, differed during months 3-36 of HAART (P=.023). Maximum CD4 cell increase from start of HAART differed by age group (P=.0003), as did maximum CD4 cell count (P<10-4). Multivariate analysis confirmed the inverse relationship between age and maximum CD4 cell response (P=.023). Time to a CD4 increase of >200x106 cells/L was shorter for patients in the younger age groups (P=.0026), as confirmed by multivariate analysis (P<10-4). Younger age may favor CD4 cell restoration because of preserved thymic function.

[Antiviral therapy of HIV infection in adults]. / Antiviral behandling av kronisk HIV-infeksjon hos voksne.

BACKGROUND: Great progress has been made in antiviral treatment of HIV disease over the last few years. MATERIAL AND METHODS: The paper is based on relevant literature and our own experience in the largest HIV clinic in Norway. RESULTS AND INTERPRETATION: Generally speaking, therapy with at least three active drugs is necessary in order to obtain maximum viral suppression. It is not established what constitutes the best starting-point for therapy, or what combination of drugs is the most efficacious. Treatment should be initiated before clinical immunodeficiency develops. All patients with CD4 counts < or = 0.2 x 10(9)/l should be offered treatment. The initial regimen should be either two nucleoside-analogues and one or two protease inhibitors, or two nucleoside-analogues and efavirenz. In order to avoid resistance and treatment failure, the patient should be thoroughly informed before and during treatment about the importance of good compliance.

Early changes in peripheral blood T cell subsets induced by antiretroviral treatment of human immunodeficiency virus-1 positive individuals.

Human immunodeficiency virus (HIV)-1 infection causes a gradual decline in peripheral blood CD4+ T cells. Shortly after the primary infection, an expansion of the activated memory CD8+ T-cell pool is also observed paralleling increased levels of plasma viraemia. In the present study we investigated the immediate effects of zidovudine therapy on peripheral blood T-cell subsets during the first 3 weeks of therapy in a group of HIV-1 positive individuals receiving influenza vaccine. HIV-1 positive individuals who received vaccine, but no treatment, were included as controls. Both the number of CD4+ and CD8+ T cells increased during the first week of therapy in parallel with a decline in plasma viraemia. The majority of CD4+ T cells contributing to this expansion expressed CD28, CD45RO and Fas, whereas the expanded CD8+ T cells were predominantly CD28-, CD45RO+, CD38+, Fas+ and Fas+ (CD95). We propose that the increase in the number of activated memory T cells observed in peripheral blood immediately after the onset of antiretroviral treatment is most likely caused by the redistribution of cells from various lymphoid organs in response to decreased levels of viral load in these compartments. The degree of T-cell redistribution is probably dependent on the magnitude of virus suppression.

A Norwegian nosocomial outbreak of methicillin-resistant Staphylococcus aureus resistant to fusidic acid and susceptible to other antistaphylococcal agents.

In Norway, infections caused by methicillin resistant Staphylococcus aureus (MRSA) are still uncommon. From December 1993 to January 1997, MRSA was isolated from 22 people in Oslo county; 17 patients and five carriers (healthcare workers). A cluster of ten people (five patients and five healthcare workers) were associated with an outbreak at two hospitals in Oslo. The five patients were all admitted to the same intensive care unit (ICU) at Ullevål University Hospital between May-July 1995 (they were not transferred from abroad) and treated for acute neurological lesions. After surgery, four of them (one died) were transferred to another hospital for rehabilitation and training. The presence of MRSA was discovered in the patients and the five healthcare workers during the 10 months June 1995-March 1996. All cluster strains showed an unusual antibiotic resistance pattern in vitro, with a relatively low degree of methicillin resistance, resistance to fusidic acid, but sensitivity to all other anti-staphylococcal agents. A clonal spread of this fusidic acid resistant MRSA was supported by strain typing using pulsed-field gel electrophoresis (PFGE), which showed that all ten cluster strains belonged to one type or its subtype.

Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group.

BACKGROUND: The introduction of combination antiretroviral therapy and protease inhibitors has led to reports of falling mortality rates among people infected with HIV-1. We examined the change in these mortality rates of HIV-1-infected patients across Europe during 1994-98, and assessed the extent to which changes can be explained by the use of new therapeutic regimens. METHODS: We analysed data from EuroSIDA, which is a prospective, observational, European, multicentre cohort of 4270 HIV-1-infected patients. We compared death rates in each 6 month period from September, 1994, to March, 1998. FINDINGS: By March, 1998, 1215 patients had died. The mortality rate from March to September, 1995, was 23.3 deaths per 100 person-years of follow-up (95% CI 20.6-26.0), and fell to 4.1 per 100 person-years of follow-up (2.3-5.9) between September, 1997, and March, 1998. From March to September, 1997, the death rate was 65.4 per 100 person-years of follow-up for those on no treatment, 7.5 per 100 person-years of follow-up for patients on dual therapy, and 3.4 per 100 person-years of follow-up for patients on triple-combination therapy. Compared with patients who were followed up from September, 1994, to March, 1995, patients seen between September, 1997, and March, 1998, had a relative hazard of death of 0.16 (0.08-0.32), which rose to 0.90 (0.50-1.64) after adjustment for treatment. INTERPRETATION: Death rates across Europe among patients infected with HIV-1 have been falling since September, 1995, and at the beginning of 1998 were less than a fifth of their previous level. A large proportion of the reduction in mortality could be explained by new treatments or combinations of treatments.

[Methicillin resistant yellow staphylococci]. / Meticillinresistente gule stafylokokker.

The incidence of methicillin-resistant Staphylococcus aureus in Norway is extremely low. Isolation of such strains is nearly always associated with import. From December 1993 to January 1997 at the Ullevål University Hospital Department of Medical Microbiology, methicillin-resistant Staphylococcus aureus was isolated from 22 persons in Oslo (17 patients and five healthy carriers). A cluster of ten infected persons was detected (five patients and five carriers (nurses)) who were infected with strains showing an unusual antibiotic resistance pattern. All of the cluster strains except for beta-lactams were resistant to fucidic acid and sensitive to other antistaphylococcal agents. The cluster was associated with two hospitals. The five patients were all admitted to the same intensive care unit during the period May to July 1995. Four of the five patients (one died) were referred to the same department in a long-term care hospital for rehabilitation and training. Problems concerning epidemiological investigation and control are discussed.