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Biomedical subjects

M Kalin

Publications and source records attributed to M Kalin.

At least 19 recordsLinked to original sources

Clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen.

BACKGROUND: Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The role of the different capsular and clonal types in invasive disease severity remains to be defined. METHODS: Disease severity and disease type were correlated to age, underlying disease, capsular serotype, and clonal type of the causative agent for 494 adult patients with invasive pneumococcal disease. RESULTS: Pneumococcal isolates of serotypes 1 and 7F were genetically homogenous, had the highest potential to infect previously healthy individuals, and were not causing deaths. Also, type 1 isolates were only found among younger adults, whereas other serotypes were mainly found among elderly persons (e.g., type 23F). Some serotypes and/or clones were more prone to cause more-severe disease, as observed by high APACHE II scores calculated at admission, and were also associated with a high mortality (e.g., clones of type 3 and 11A). We found no evidence of an impact of penicillin resistance on disease severity and disease type. CONCLUSIONS: We suggest that clones with capsular types 1 and 7F, which are known to have a high invasive disease potential, behave as primary pathogens, whereas clones with other capsular types with a lower relative risk of causing invasive disease are more opportunistic, primarily affecting patients with underlying disease. Disease caused by the latter group, however, was more severe, even in previously healthy individuals.

Adult↗

Addition of a macrolide to a ss-lactam in bacteremic pneumococcal pneumonia.

In the study presented here, data collected prospectively from 340 adult patients hospitalised in five countries with bacteremic pneumococcal CAP and treated with a ss-lactam +/- a macrolide were analysed retrospectively to evaluate the efficacy of this antimicrobial combination. Univariate and multivariate analyses revealed no significant effect on case fatality rate when a macrolide/ss-lactam regimen was used as initial therapy. Results were not affected by severity of illness, or by excluding patients who died within 2 days of admission. Identified predictors of death in a multivariate regression model were age >65 years (OR=2.6), two or more lung lobes affected (OR=2.2), and severity of disease as estimated using the acute physiology score (APS)>8.

Adult↗

A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma.

BACKGROUND: Splenectomy is accompanied by a life-long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune-mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA). METHODS: A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay technique the patients were revaccinated with 23-valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month +/- 2 weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a national population-based database, and microbiological databases were checked for 124 HL patients to identify OPSI. RESULTS: A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow-up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle-aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7-year period. CONCLUSIONS: A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype-specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1-5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.

Adolescent↗

Different trends in antibiotic resistance rates at a university teaching hospital.

OBJECTIVES: To investigate long-term trends in antibiotic resistance of common bacterial species isolated at a university hospital and in its intensive care units (ICUs). METHODS: Levels of antibiotic resistance of common bacterial pathogens were investigated at the Karolinska Hospital during the 12-year period 1988-99. Resistance rates were analyzed for the entire hospital, as well as for ICUs combined. RESULTS: At the Karolinska Hospital, we found increased ciprofloxacin resistance among Escherichia coli isolates, from 0% in 1991 to 11% in 1999. In the ICUs, the corresponding increase was from 0% to 4.8% during the same period. Co-trimoxazole resistance levels increased from 7.5% to 14%, with lower levels for the ICUs. For ampicillin, cefuroxime, and gentamicin, the levels of resistance were similar in the whole hospital and in the ICUs. Among Pseudomonas aeruginosa isolates, imipenem resistance was higher in the ICUs. For ciprofloxacin, resistance increased from 2.5% in 1991 to 13% in 1999 in the whole hospital, with similar figures for the ICUs. CONCLUSION: The resistance rates at the Karolinska Hospital were still generally low, but were increasing for some antibiotic-microbe combinations. The results emphasize the importance of including all sectors of a hospital in resistance surveillance studies, and also the value of long surveillance periods.

Anti-Bacterial Agents↗

Dynamics of penicillin-susceptible clones in invasive pneumococcal disease.

In a 10-year period, 1987-1997, there was a >4-fold increase in the rate of pneumococcal bacteremia in Sweden. Invasive pneumococcal isolates (n=1136), which were obtained from 18 Swedish clinical microbiology laboratories from 1987 through 1997, and other national and international isolates were serotyped, and their clonal relationships were determined by molecular typing. The increase in invasive pneumococcal disease in Sweden during this period was associated particularly with an increase in isolates of serotypes 1 and 14. A 3-fold increase of type 14 was seen from 1987 through 1992, and a 10-fold increase of type 1 occurred from 1992 through 1997. One dominating penicillin-susceptible clone of type 14 was responsible for the increase of type 14 during the first 5 years. This clone also was found in Canada and the United States and was shown by multilocus sequence typing to correspond to a previously identified hyper-virulent clone. A novel penicillin-susceptible clone of type 1, which was not found among invasive isolates from 1987 or 1992, was responsible for the increase of serotype 1 during the last 5 years. These results illustrate the ability of virulent penicillin-susceptible pneumococcal clones to emerge and spread rapidly within a country.

Alleles↗

[Prophylactic and empirical treatment of mycoses in neutropenic fever. Report and comments on meta-analysis].

Patients treated for cancer with chemotherapy and other cytoreductive therapy often develop serious bacterial, viral, and fungal infections due to B- and T-cell depletion, neutropenia and decreased barrier function of mucosal membranes. In patients with neutropenic fever not responding to broad spectrum antibiotic therapy there is a high risk of fungal infection. In a Cochrane Library meta-analysis of the effect of prophylactic and empirical antifungal treatment, amphotericin B was found to be the only drug affecting total mortality. Fluconazole, ketoconazole and itraconazole affected risk of colonization and invasive infection, but not the total risk of death. We agree with these conclusions, but emphasize that the appropriate time to initiate empirical antifungal therapy is still not settled. We also believe that azoles may be of value in the therapy of symptomatic mucositis.

Amphotericin B↗

Outpatient parenteral antibiotic therapy in patients with haematological malignancies. A pilot study of an early discharge strategy.

The objectives of this study were to estimate the feasibility of a self-administration outpatient parenteral antibiotic therapy (OPAT) model. to record the complication rate and to estimate patient acceptance during the OPAT period in patients with acute leukaemia (AL) or aggressive non-Hodgkin lymphoma (NHL). Patients were trained to administer the antibiotic infusions themselves, via their central venous access device, according to a checklist and step-by-step instructions. Study-specific questionnaires were used to evaluate patient acceptance. Eleven patients [AL (n=8) and NHL (n=3), median age 51 years, range 29-661 participated in the education programme and subsequent OPAT during ten episodes of documented infection and six episodes of fever of unknown aetiology. All patients had assessment of the infectious episode and initial parenteral antibiotic therapy in the hospital before they continued self-administration at home. The median education time was 3 h (range 0.75-4.5). The patients could stay at home for 4 days (median, range; 1-12) with ongoing intravenous antibiotic therapy instead of being hospitalised. None of the patients developed recurrent fever. All patients reported that OPAT was of great value and they would favour OPAT again during subsequent antibiotic therapy. In conclusion, the results of this pilot series suggest that OPAT, in this setting, is a safe alternative during the last days of an episode of fever / infection. All patients were satisfied overall, and none was readmitted.

Adult↗

Development of the phytoplankton community in a pit-lake in relation to water quality changes.

An open pit-lake was formed at a Northern Saskatchewan mine site after flooding with lake water in early 1992. Since then, water and phytoplankton samples have been collected regularly from the artificial lake over seven years. The resulting data set provides a unique opportunity to examine the physical and chemical changes in water quality and phytoplankton community over time. Seventeen major variables were examined in a principal component analysis. Axes 1, 2 and 4 are significantly correlated to other three variables, the number of days (since the first sampling after flooding of the pit), water temperature and depth, respectively. Total suspended solid (TSS), dissolved oxygen, total phosphorus (Total-P), arsenic, and iron decreased over time while Mg, Ca, K, Na, total organic carbon and HCO3 increased. Canonical correspondence analysis was used to infer the relationship between water quality variables and phytoplankton community structure, which changed substantially over the survey period. TSS, Total-P and arsenic were considered to be the key factors driving the change in phytoplankton community composition.

Canada↗

Biogeochemical and ecological considerations in designing wetland treatment systems in post-mining landscapes.

Although wetlands have gained acceptance as important components of ecosystems in post-mining landscapes in the past decade, their roles in contaminant retention/removal have not been well integrated into the designing of restoration programs. This paper describes the integration of sediment microbial activities and natural precipitation processes, along with approaches to defining the contaminant load from the mine wastes. The contaminant removal rates, which can be expected by a wetland sediment, are summarized and how they need to be reflected in the wetland size required, and the carbon supply which is needed. Contaminant loading from mining wastes can be balanced by wetland ecological processes, including wetland primary production and microbial mineralization in the sediment. This ecological engineering approach is demonstrated using case studies on hard-rock mining waste in Canada.

Canada↗

Liposomal amphotericin B and surgery in the successful treatment of invasive pulmonary mucormycosis in a patient with acute T-lymphoblastic leukemia.

Pulmonary mucormycosis is a usually fatal opportunistic infection in immunocompromised patients. We describe the first case of an adult patient with hematological malignancy and profound neutropenia to survive a disseminated pulmonary Rhizomucor pusillus infection. Early diagnostic procedures combined with high doses of liposomal amphotericin B and surgical resection may have contributed to the successful outcome.

Amphotericin B↗

Changes in serotype distribution may hamper efficacy of pneumococcal conjugate vaccines in children.

During the last 10 y we have observed an increased incidence of pneumococcal bacteremia in Sweden. In order to study the serotype distribution over time we collected 1136 invasive pneumococcal isolates from 1987, 1992 and 1997 from Swedish microbiological laboratories. Currently, new pneumococcal conjugate vaccines are being considered for introduction in the general childhood vaccination program in several countries, including Sweden. We studied the potential vaccine coverage rate for the new conjugate vaccines among our Swedish invasive isolates. We found that the serotype distribution fluctuated with time and observed a surprisingly low potential coverage rate for the 7-valent vaccine in Sweden, in contrast to other countries. Therefore we argue that pneumococcal conjugate vaccines have to be tailored to suit current, local serotype patterns and most likely will need to be changed over time.

Adolescent↗

Prospective study of prognostic factors in community-acquired bacteremic pneumococcal disease in 5 countries.

To define the influence of prognostic factors in patients with community-acquired pneumococcal bacteremia, a 2-year prospective study was performed in 5 centers in Canada, the United States, the United Kingdom, Spain, and Sweden. By multivariate analysis, the independent predictors of death among the 460 patients were age >65 years (odds ratio [OR], 2.2), living in a nursing home (OR, 2.8), presence of chronic pulmonary disease (OR, 2.5), high acute physiology score (OR for scores 9-14, 7.6; for scores 15-17, 22; and for scores >17, 41), and need for mechanical ventilation (OR, 4.4). Of patients with meningitis, 26% died. Of patients with pneumonia without meningitis, 19% of those with >/=2 lobes and 7% of those with only 1 lobe involved (P=.0016) died. The case-fatality rate differed significantly among the centers: 20% in the United States and Spain, 13% in the United Kingdom, 8% in Sweden, and 6% in Canada. Differences of disease severity and of frequencies and impact of underlying chronic conditions were factors of probable importance for different outcomes.

Aged↗

Molecular epidemiology of Streptococcus pneumoniae causing invasive disease in 5 countries.

A multicenter study was done during 1993-1995 to investigate prospectively the influence of several prognostic factors for predicting the risk of death among patients with pneumococcal bacteremia. Five centers located in Canada, the United Kingdom, Spain, Sweden, and the United States participated. Clinical parameters were correlated to antibiotic susceptibility and serotyping of the 354 invasive pneumococcal isolates collected and to molecular typing of 173 isolates belonging to the 5 most common serotypes (14, 9V, 23F, 3, and 7F). Serotype 14 was the most common among all isolates, but serotype 3 dominated in fatal cases and in isolates from Spain and the United States, the countries with the highest case-fatality rates. Fewer different patterns were found among the type 3 isolates, which suggests a closer clonal relationship than that among isolates belonging to other serotypes. Of type 3 isolates from fatal cases, 1 clone predominated. Other penicillin-susceptible invasive clones were also shown to spread in and between countries.

Adult↗

Recurrence of pneumonia in relation to the antibody response after pneumococcal vaccination in middle-aged and elderly adults.

We have recently studied the efficacy of pneumococcal vaccine in preventing pneumonia recurrences after hospital treatment for community-acquired pneumonia in non-immunocompromised patients aged 50-85 y. Among these patients, we have now compared the antibody response to the pneumococcal vaccine between patients who developed pneumonia (n = 50) and patients without pneumonia recurrences (n = 100), during a mean follow-up period of 32 months after vaccination. The antibody levels of 5 pneumococcal serotypes were measured before, and 4 weeks, 1 y and 3 y after vaccination. A lower risk of pneumonia recurrences was seen in patients with antibody fold increases (FIs) > 4 from pre-vaccination to post-vaccination compared with patients with lower FIs (p = 0.02). The results suggest that in this patient category, the antibody response to pneumococcal vaccination is of importance for the risk of pneumonia recurrence.

Aged↗

Bioavailability of aciclovir after oral administration of aciclovir and its prodrug valaciclovir to patients with leukopenia after chemotherapy.

The median bioavailabilities of aciclovir after administration of aciclovir and its prodrug valaciclovir were 21.5 and 70.1%, respectively, in 12 patients with malignant hematological diseases with leukopenia after chemotherapy. The interindividual variations of the bioavailability were 48.5 and 21.0% after administration of aciclovir and valaciclovir, respectively. Neither the bioavailability nor the interindividual variation of area under the concentration-time curve of oral aciclovir or valaciclovir differed from that reported in healthy volunteers.

Acyclovir↗

[The elderly should be vaccinated against pneumococci].

Invasive pneumococcal diseases are associated with substantial mortality in the elderly. The incidence of such diseases, particularly that of bacteraemic pneumococcal pneumonia, has increased in Sweden during the past decade. At the same time, there is a growing problem with beta-lactam-resistant and multiresistant pneumococci in many nearlying countries. Although pneumococcal vaccine probably provides only limited protection against pneumococcal pneumonia in the elderly, it yields approximately 70 per cent protection against invasive pneumococcal disease. Pneumococcal vaccination should therefore be recommended to all those 65 years old and above, and a nationwide strategy developed to implement good coverage in the age group.

Aged↗

Successful extracorporeal membrane oxygenation in four children with malignant disease and severe Pneumocystis carinii pneumonia.

BACKGROUND: Toxic deaths due to intensified treatment are of increasing concern in view of the generally improved prognosis for children with malignancies. Pneumocystis carinii pneumonia (PCP) during immunosuppressive treatment in children with malignancies is a severe complication with a poor prognosis if mechanical ventilation is required. Extracorporeal membrane oxygenation (ECMO) is a recognized technique that provides temporary respiratory support for patients with intractable respiratory failure. PROCEDURE: We here report successful ECMO support in four children with PCP, secondary to chemotherapy-induced immunosuppression, in whom the respiratory situation deteriorated despite pharmacological treatment and mechanical ventilation. The duration of ECMO was 7-43 days. RESULTS: Three children with acute lymphoblastic leukemia recovered from their PCP to continue chemotherapy and are now in complete continuous remission. Their pulmonary function normalized completely during 6-12 months after ECMO therapy. One child with a primitive neuroectodermal tumor survived the PCP and was off ECMO for 11 days before succumbing to unrelated complications. CONCLUSIONS: We conclude that ECMO offers an important means of respiratory support in children with severe PCP that can also be adopted during treatment for malignant disease.

Adolescent↗