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Biomedical subjects

M Kalin

Publications and source records attributed to M Kalin.

At least 37 records · Page 2Linked to original sources

Cefepime as empirical monotherapy in febrile patients with hematological malignancies and neutropenia: a randomized, single-center phase II trial.

The purpose of this phase II trial was to evaluate the efficacy and safety of cefepime monotherapy in patients with neutropenia expected to last more than 7 days. Sixty-nine patients with neutropenia (<0.5 x 10(9)/1) were randomized during 94 episodes of fever to receive either cefepime monotherapy (n=76) or combination therapy with trimethoprim/sulfamethoxazole plus amikacin (TMP/SMZ plus AMI, n=18). A successful response to cefepime was seen in 31/76 (41%) episodes, with 10/36 (28%) in microbiologically documented infections, 3/4 (75%) in clinically documented infections and 18/36 (50%) in fever of unknown origin. No patient in either treatment group died due to the presenting infection. One patient in the cefepime group discontinued treatment due to a rash. Susceptibility testing of blood isolates by E-test strip showed low MIC values to cefepime for most isolates. It is concluded that cefepime monotherapy appeared both safe and effective as empirical therapy in patients with febrile neutropenia.

Adolescent↗

Three cases of canine leptospirosis in Quebec.

Three dogs from different locations with acute renal failure were hospitalized in autumn 1996 and 1997. Leptospira interrogans serovar pomona was detected by the microscopic agglutination test. All dogs recovered after antibiotic treatment. The importance of the development of vaccines adapted to emerging serovars in dogs should be addressed.

Agglutination Tests↗

Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish Pneumococcal Vaccination Study Group.

BACKGROUND: We assessed the effectiveness of a 23-valent pneumococcal vaccine in the prevention of pneumococcal pneumonia and of pneumonia overall in non-immunocompromised middle-aged and elderly people. METHODS: The prospective, multicentre, double-blind, randomised, placebo-controlled trial was carried out across departments of infectious diseases at six tertiary-care or university hospitals in Sweden. 691 non-immunocompromised patients aged 50-85 years who had been treated as inpatients for community-acquired pneumonia (CAP) were randomly assigned either 23-valent pneumococcal capsular polysaccharide vaccine or placebo (sodium chloride). We used Cox regression models to estimate the relative risks of pneumonia overall and pneumococcal pneumonia for the placebo group compared with the vaccine group. FINDINGS: 63 (19%) of 339 patients in the vaccine group and 57 (16%) of 352 patients in the placebo group developed a new pneumonia, corresponding to a relative risk over time for the placebo group compared with the vaccine group of 0.83 (95% CI 0.58-1.12, p=0.31). Pneumococcal pneumonia was diagnosed in 16 (4.5%) patients in the placebo group and in 19 (5.6%) in the vaccine group, corresponding to a relative risk for the placebo group of 0.78 (95% CI 0.40-1.51, p=0.45). We found no difference in the death rate between the two study groups. INTERPRETATION: The 23-valent pneumococcal polysaccharide vaccine did not prevent pneumonia overall or pneumococcal pneumonia in middle-aged and elderly individuals.

Aged↗

Low incidence of candidaemia among neutropenic patients treated for haematological diseases.

Candida colonization and haematogenous infection were studied retrospectively in 277 patients with haematological diseases by reviewing the microbiological reports of fungal surveillance and blood cultures over a 4-year period. Most patients (83%) were colonized by Candida and in the majority (68%) the same Candida species was isolated from at least 2 body sites. However, candidaemia was diagnosed in only 3 patients. During the same period invasive aspergillosis was diagnosed in 7 patients. Possible causes for the low incidence of candidaemia were fluconazole prophylaxis, empirical amphotericin B and strict indication for antibacterial therapy.

Adolescent↗

Recurrence of pneumonia in middle-aged and elderly adults after hospital-treated pneumonia: aetiology and predisposing conditions.

In order to investigate the predisposing conditions and aetiologic agents in patients with recurrent pneumonia, we prospectively studied 653 immunocompetent patients, 50-85 years of age, who had been treated in hospital for community-acquired pneumonia. After an average patient follow-up period of 32 months, 11 variables were examined for association with the following end points: death, recurrence of pneumonia and recurrence of pneumococcal pneumonia. During the follow-up period there were 171 episodes of pneumonia in 115 of the 653 patients, and 52 deaths (all causes). Multivariate analysis showed that age, male sex, congestive heart failure and presence of other chronic diseases were significantly associated with higher mortality. Age and chronic pulmonary disease were associated with recurrence of pneumonia. The major aetiologic agents were Streptococcus pneumoniae (26%), Haemophilus influenzae (11%) and Moraxella catarrhalis (6%). We conclude that pneumonia recurrences are common in middle-aged and elderly patients after treatment in hospital for community-acquired pneumonia. The recurrence risk is higher in elderly patients, and in those with chronic pulmonary diseases. Given the prominence of H. influenzae and M. catarrhalis found in the present study, these organisms should always be considered when choosing the initial antibiotic in patients with recurrent pneumonia.

Age Factors↗

Clinical and laboratory diagnosis of invasive candida infection in neutropenic patients.

Cancer patients, especially those with acute leukaemia, represent a group that has the greatest risk for deep fungal infection. Almost no cases were seen before the advent of modern chemotherapy, and prior to the availability of antibacterial agents, less than 5% of patients with acute leukaemia died of fungal infection. These infections are now responsible for 40% or more of the deaths at some institutions. Candida species continues to be the most common fungal pathogen. Rapid and specific diagnosis of invasive candiosis enabling early effective therapy is therefore an important measure for reducing mortality in patients. Here the current status of clinical and laboratory diagnosis of invasive candida infection in neutropenic patients is discussed and recommendations made as to future development programmes.

Antineoplastic Agents↗

Imipenem/cilastatin monotherapy as salvage treatment in febrile neutropenic patients.

Imipenem/cilastatin (I/C) monotherapy was used as salvage treatment in 55 neutropenic patients (58 fever episodes) after treatment failure on first-line antibiotic therapy. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiologic evidence of infection on I/C monotherapy alone. Twenty-five out of the 58 episodes (43%) were classified as success, 6 episodes (10%) as initial response but the regimen had to be modified (amphotericin B was added) and 27 episodes (47%) as failures. In episodes with documented infections 9 out of 23 (39%) were classified as success. All patients survived during the first 72 hours after change to I/C therapy. One patient had to discontinue I/C due to a skin rash. In conclusion, the use of a treatment algorithm with I/C monotherapy as second-line treatment was safe and effective. Other antimicrobial agents, most often vancomycin and/or amphotericin B, had to be added in half of the patients.

Adolescent↗

Trimethoprim-sulfamethoxazole plus amikacin versus ceftazidime monotherapy as empirical treatment in patients with neutropenia and fever.

In a prospective randomized comparison, 217 episodes of fever (oral temperature > 38.5 degrees C on 1, or 38.0 degrees C on 2 occasions with a minimum interval of 4 h between recordings) during neutropenia (neutrophil count < 0.5 x 10(9)/I), patients were empirically treated with trimethoprim-sulfamethoxazole plus amikacin (TMP/SMZ plus AMI) or ceftazidime. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiological evidence of infection on the primary therapy alone. The overall success rate did not differ between the 2 treatment groups: 31/102 (30%; 21-39%, 95% confidence interval, CI) for TMP/SMZ plus AMI and 41/115 (36%; 27-44%) for ceftazidime (difference 0.06 +/- 0.13, 95% CI). The corresponding numbers for documented infections were 12/50 (24%; 12-36%) and 14/60 (23%; 12-35%), respectively (difference 0.01 +/- 0.16). One patient in the TMP/SMZ plus AMI group and 2 patients in the ceftazidime group died from Gram-negative bacteraemias within 72 h. No other early deaths were observed. Antibiotics were changed due to adverse events in 2 episodes of each treatment group. In conclusion, this study demonstrates that TMP/SMZ plus AMI combination is comparable (i.e. a difference of < 20%) to ceftazidime monotherapy with regard to efficacy and safety in haematological patients with severe neutropenia. Both regimens require frequent modifications, particularly in bacteraemic fever episodes. However, in centres with a low frequency of isolation of Pseudomonas and especially of multi-resistent Pseudomonas strains, TMP/SMZ plus AMI offers an inexpensive alternative for the empirical treatment of febrile neutropenia.

Adolescent↗

Systemic amphotericin B versus fluconazole in the management of antibiotic resistant neutropenic fever--preliminary observations from a pilot, exploratory study.

A pilot exploratory study was undertaken to collect preliminary information relating to safety and overall outcome in using intravenous fluconazole (FLUC) for managing antibiotic resistant neutropenic fever (ARNF), with the objective of assessing feasibility of performing a larger prospective controlled study. Patients who were neutropenic from treatment for leukaemia or bone marrow transplantation, received either fluconazole (FLUC) or amphotericin B (AB). Eight of 16 patients (50%) on FLUC and 21 of 25 patients (84%) on AB defervesced; the mean time to defervescence was 11.0 +/- 10.0 days for FLUC compared to 7.7 +/- 6.3 days for AB, and a similar proportion in each treatment group defervesced within 5 days (50% vs. 52%), respectively. Six of 16 patients (37.5%) on FLUC and three of 25 patients (12%) on AB developed overt invasive fungal disease, including pulmonary aspergillosis (FLUC 4 cases, AB 2 cases) and invasive candidiasis (FLUC 2 cases, AB 0 cases). The mean time to these events was 19.5 +/- 13.4 (FLUC) and 9.0 +/- 3.6 (AB) days. The fungal related mortality rates were higher in the FLUC group: five of 16 patients (31%) vs. two of 25 patients (18%) died respectively; the time to fungal death was 43.2 +/- 18.2 (FLUC) and 25.0 +/- 18.4 (AB) days. This tendency towards a more favourable outcome in patients on AB may have been due to absence of prior fluconazole prophylaxis in patients subsequently receiving IV FLUC. Analysis of a small subgroup of patients who had all received prior prophylaxis with clotrimazole only, indicated that a greater number of patients subsequently receiving IV FLUC died from fungal disease (5/16 vs.0/6, P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Incidence, capsular types, and antibiotic susceptibility of invasive Streptococcus pneumoniae in Sweden.

The number of reported cases of invasive pneumococcal infections in Sweden increased more than threefold from 1988 through 1992. We studied the capsular types and the antibiotic susceptibility of 619 pneumococcal strains isolated from blood or CSF at 18 Swedish microbiological laboratories in 1987 and in 1992. These strains belonged to 35 of the 84 recognized capsular types. We noted a remarkable increase in the prevalence of invasive infections with type 14 from 1987 (8.2%) to 1992 (18%) (P = .001), which correspond to a sevenfold increase in absolute numbers. The most prominent increase in infections was seen among elderly people; in 1992, type 14 accounted for 22.5% of the isolates from infected persons who were >64 years of age. The majority of the strains were susceptible to all antibiotics tested. However, there was a significant increase in trimethoprim-sulfamethoxazole resistance from 1.4% in 1987 to 7.1% in 1992. Nine multiresistant isolates (1.5%) were found.

Adolescent↗

Diagnostic and prognostic value of interleukin-6 and C-reactive protein in community-acquired pneumonia.

The diagnostic and prognostic value of admission serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) was investigated in 203 hospital-treated patients with community-acquired pneumonia (CAP). In serum samples obtained during the first 24 h after admission, IL-6 was detectable in 198 patients (98%), with a median value of 50 ng/l. Ten % of the patients had IL-6 values of 1000 ng/l. A clear positive correlation between IL-6 and CRP was found (r = 0.29, p < 0.0001). Patients with high IL-6 or CRP levels had longer duration of fever, longer hospital stay, and had less often recovered clinically or radiographically on follow-up weeks after discharge. A high IL-6, but not a high CRP, also seemed to be associated with a higher mortality. Bacteremic pneumococcal pneumonia had the highest levels of IL-6 (mean 2852 and median 420 ng/l) and CRP (mean 292 and median 285 mg/l). High IL-6 values were also seen in patients with non-bacteremic pneumococcal pneumonia, while all patients with pneumonia due to other bacterial, or viral, aetiology had IL-6 levels of < or = 300 ng/l. In conclusion, IL-6 and CRP are promising diagnostic and prognostic tools in the management of CAP. Further studies are needed to establish the usefulness of repeated measurements early in the hospital course of the disease.

Bacteremia↗

Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients.

The efficacy and safety of oral fluconazole versus a polyene regimen in preventing mycoses in neutropenic patients was compared. Patients with haematological malignancy or bone marrow transplantation received as antifungal prophylaxis either fluconazole 200 mg daily or a regimen consisting of clotrimazole trouches 10 mg twice daily with mycostatin, 500,000 I.U. four times daily, benadryl and cepacol mouthwash. Ninety patients at risk for fungus infection were evaluable. Four of 42 patients (9.5%; confidence interval 2%-23%) on fluconazole and 17 of 48 patients (35.4%; confidence interval 22%-52%) (p < 0.01) on the clotrimazole regimen developed a clinically significant fungal infection, including 3 (7.1%) and 11 (22.9%) patients respectively who had severe fungal infection, mainly pulmonary aspergillosis. Death directly due to a fungal infection within 100 days of the start of prophylaxis occurred in 2 of 42 patients (4.8%) and 9 of 48 patients (18.8%) respectively (p < 0.06). Kaplan-Meier analysis showed that the chance of survival on fluconazole was statistically greater than for the clotrimazole regimen (p < 0.04). A decrease of candidal colonisation of the gastrointestinal and genitourinary tracts occurred only in patients receiving fluconazole. No significant toxicity occurred. A 200 mg daily dose of fluconazole given to these patients thus appears to be well tolerated and to provide a protective effect against the development of fungal infection and death from severe fungal disease.

Adolescent↗

The role of IgA determination by ELISA in the early serodiagnosis of Mycoplasma pneumoniae infection, in relation to IgG and mu-capture IgM methods.

Enzyme-linked immunosorbent assay (ELISA) for IgA, IgG and IgM was evaluated with sera from 50 adult patients with pneumonia, selected on the basis of a positive complement fixation (CF) test for diagnosis of Mycoplasma pneumoniae infection and with sera from 105 healthy blood donors. The ELISA antigen for IgG and IgA was a sonicated suspension of M. pneumoniae solubilised by deoxycholate. For the IgM assay, the same antigen was directly conjugated to alkaline phosphatase and used in a mu-capture format. ELISA gave positive results with high or rising titres for one or several antibody classes in 47 (94%) patients. In two of the three ELISA-negative cases, the diagnosis of M. pneumoniae infection indicated by the CF test seemed unlikely on clinical grounds. Specific IgA antibodies was developed more regularly and more rapidly than IgM. IgA titres also started to decrease earlier than IgM or the late-peaking IgG response. Thus, the determination of IgA antibodies was found to be valuable for the early diagnosis of M. pneumoniae infection. The study also demonstrated that the determination of all three antibody classes is necessary to obtain an optimal level of serodiagnosis.

Adolescent↗