Poor Correlation between Pneumococcal IgG and IgM Titers and Opsonophagocytic Activity in Vaccinated Patients with Multiple Myeloma and Waldenstrom's Macroglobulinemia.

Patients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n= 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [r] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group (r= -0.18 to 0.21) or in the group with Waldenstrom's macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes (r= 0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstrom's macroglobulinemia patients.

A clinical study of culture-negative endocarditis.

Culture-negative infective endocarditis (CNE) is a diagnostic problem in spite of improved echocardiographic and blood culturing techniques. We conducted the present study to estimate the proportion of CNE in patients with infective endocarditis, to investigate data regarding risk factors, and to evaluate the Duke and the modified Beth Israel criteria in patients with CNE. We evaluated 820 consecutive suspected episodes of infective endocarditis in adults at the Departments of Infectious Diseases in Göteborg and Borås, Sweden (1984-1996). All patients were diagnosed and treated according to a protocol; 487 episodes were identified as infective endocarditis. Episodes with absence of bacterial growth at blood culture were defined as CNE and were classified with the Duke and the modified Beth Israel criteria. We identified 116 CNE episodes (median age, 67 yr). Mortality was 7%, and in 15%, cardiac surgery was performed. The Duke criteria classified 20 definite, 80 possible, and 16 reject episodes. The modified Beth Israel criteria distinguished 13 definite, 15 probable, 27 possible, and 61 reject episodes. The proportion of CNE among patients with infective endocarditis varied from 19% to 27% at the 2 departments. Antibiotic treatment preceded blood culture in 45% of the CNE episodes. About 20% in a Scandinavian population of infective endocarditis patients have CNE. Antibiotic pretreatment explains less than 50% of all CNE episodes. The Duke criteria are more sensitive but less specific than the modified Beth Israel criteria in classifying patients with CNE.

Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance.

Whereas patients with multiple myeloma (MM) have a well-documented susceptibility to infections, this has been less studied in other B-cell disorders, such as Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS). We investigated the humoral immunity to 24 different pathogens in elderly patients with MM (n = 25), WM (n = 16), and MGUS (n = 18) and in age-matched controls (n = 20). Antibody titers against pneumococci, staphylococcal alpha-toxin, tetanus and diphtheria toxoids, and varicella, mumps, and rubella viruses were most depressed in MM patients, next to lowest in WM and MGUS patients, and highest in the controls. In contrast, levels of antibodies specific for staphylococcal teichoic acid, Moraxella catarrhalis, candida, aspergillus, and measles virus were similarly decreased in MM and MGUS patients. Comparable titers in all study groups were seen against Haemophilus influenzae type b (Hib), borrelia, toxoplasma, and members of the herpesvirus family. Finally, a uniform lack of antibodies was noted against Streptococcus pyogenes, salmonella, yersinia, brucella, francisella, and herpes simplex virus type 2. To conclude, although MM patients displayed the most depressed humoral immunity, significantly decreased antibody levels were also evident in patients with WM and MGUS, particularly against Staphylococcus aureus, pneumococci, and varicella. Conversely, immunity was retained for Hib and certain herpesviruses in all study groups.

A 10-year survey of blood culture negative endocarditis in Sweden: aminoglycoside therapy is important for survival.

We estimated the prevalence of blood culture negative endocarditis (CNE) and described and analysed data with special attention to antibiotic treatment from patients with infective endocarditis (IE) reported to the Swedish endocarditis registry during the 10-y period 1995-2004. All 29 departments of infectious diseases in Sweden reported data to the registry. During the 10-y period, 2509 IE episodes (78% Duke definite) were identified in 2410 patients. 304 CNE episodes (25% Duke definite) were found. The proportion of CNE was measured to be 12% of all IE episodes. Fatal outcome occurred in 10.7% of all IE patients and in 5% of the CNE patients. The risk of dying was significantly increased in female (9%) compared to male (2%) CNE patients (OR 5.1). Mortality was significantly decreased in patients treated with an aminoglycoside (3%) versus patients without aminoglycoside therapy (13%), OR 0.2. In conclusion, the prevalence of CNE was 12% in Swedish IE patients in a 10-y survey. The mortality in IE was low (10.7%) and 4.6% for CNE. Women have higher mortality rates than men in CNE. CNE patients who received aminoglycoside therapy survived more frequently than CNE patients without this therapy.

Swedish guidelines for diagnosis and treatment of infective endocarditis.

Swedish guidelines for diagnosis and treatment of infective endocarditis (IE) by consensus of experts are based on clinical experience and reports from the literature. Recommendations are evidence based. For diagnosis 3 blood cultures should be drawn; chest X-ray, electrocardiogram, and echocardiography preferably transoesophageal should be carried out. Blood cultures should be kept for 5 d and precede intravenous antibiotic therapy. In patients with native valves and suspicion of staphylococcal aetiology, cloxacillin and gentamicin should be given as empirical treatment. If non-staphylococcal etiology is most probable, penicillin G and gentamicin treatment should be started. In patients with prosthetic valves treatment with vancomycin, gentamicin and rifampicin is recommended. Patients with blood culture negative IE are recommended penicillin G (changed to cefuroxime in treatment failure) and gentamicin for native valve IE and vancomycin, gentamicin and rifampicin for prosthetic valve IE, respectively. Isolates of viridans group streptococci and enterococci should be subtyped and MIC should be determined for penicillin G and aminoglycosides. Antibiotic treatment should be chosen according to sensitivity pattern given 2-6 weeks intravenously. Cardiac valve surgery should be considered early, especially in patients with left-sided IE and/or prosthetic heart valves. Absolute indications for surgery are severe heart failure, paravalvular abscess, lack of response to antibiotic therapy, unstable prosthesis and multiple embolies. Follow-up echocardiography should be performed on clinical indications.

Bartonella and Coxiella antibodies in 334 prospectively studied episodes of infective endocarditis in Sweden.

Bartonella spp. have been identified as aetiological agents in culture-negative infective endocarditis (IE). Coxiella burnetii may cause chronic Q-fever with endocarditis, 334 blood samples collected from 329 patients (334 episodes) with IE diagnosed between 1984 and 1996 in Göteborg, Sweden, were investigated for antibodies to Bartonella spp. and C. burnetii. 71 of the episodes (21%) were blood culture negative. A microimmunofluorescence assay revealed immunoglobulin G (IgG) antibodies to Bartonella in 13 of the culture verified episodes and in 2 of the culture-negative episodes. Three of the patients had IgG antibodies to > or = 200 in the blood culture-verified group, but none had a titre > or = 800, the cut-off level for Bartonella endocarditis. One patient had elevated antibodies to C. burnetii, diagnosing chronic Q-fever endocarditis. In conclusion, serologically verified Bartonella endocarditis is not prevalent in western Sweden and Q-fever endocarditis is rare.

Pacemaker endocarditis during 18 years in Göteborg.

Pacemaker endocarditis is a rare but serious complication. Few studies addressing its treatment have been published. Clinical characteristics and outcome were retrospectively studied in 38 patients with 44 episodes of pacemaker infective endocarditis (PMIE) in Göteborg, during 1984-2001. The male/female ratio of episodes was 27/17 and the mean age 69 y. Transthoracic echocardiography (TTE) showed vegetation in 4/22 (18%) episodes and transoesophageal echocardiography (TEE) in 22/33 (67%). Staphylococci were isolated in 66% of blood cultures. The pacemaker system (PS) was removed in 28 episodes and in 18 of these there were no signs of reinfection at follow-up. In 16 episodes the PS was not removed, and in 13 of these, signs of infection were found at follow-up. Thus, the present study of PMIE showed staphylococci to be predominant causative agents and demonstrated a high diagnostic sensitivity of TEE. According to our results, PM removal rather than conservative treatment should be considered in all cases.