[Two-step tuberculin testing and BCG vaccination in the personnel of a medical and pharmaceutical university].

In an attempt to cope with recent nosocomial spread of tuberculosis, the tuberculin test with a 0.05 microgram of 0.1 ml intradermal dose of purified protein derivative was performed by a two-step procedure on the personnel of a medical and pharmaceutical university, followed by BCG vaccination for non-reactors in the second test. The second test was repeated after two weeks in all but those with erythema of 10 mm or more in diameter associated with double erythema, vesicle formation, and/or necrosis on the initial testing. The first test was done in a total of 935 participants (73% of all personnel) with a median age of 37 (range, 21-67) years. The rate of participation, by occupation, in the hospital personnel ranged from 63% (183/289) for doctors to 98% (351/358) for nurses. The size of erythema showed a unimodal distribution with a peak in the range of 10-19 mm, with a median of 20 mm (range, 0-102). Reactions below 9 mm, which are interpreted as negative, were found in 16% of all participants, and those above 30 mm in 35%. Among participants aged 20-49 years, especially among nurses, reactions tended to be larger with increasing age. Among 539 participants undergoing repeated testing, reactions between the first and second tests correlated well, showing a median increase in size of 10 mm (range, -43-(+)70) on retesting. Reactions above 30 mm associated with an increase in size larger than 20 mm, among those initially below 29 mm in diameter, were observed in 28% of those retested. Adverse reactions such as vesicle formation with or without hemorrhage, or lymphangitis occurred in 2.5% of all participants on the initial testing and in 1.5% on the retesting, with the highest frequency seen in those aged 30-39 years. BCG was administered to 26 of the 49 participants with a negative reaction on the second test. All vaccinees with a median age of 30 (range, 21-46) years showed tuberculin conversion after two months without developing Koch's phenomenon soon after the vaccination. Incidentally, it is desirable that two-step tuberculin testing such as that in the present study should also be performed using the diameter of induration, particularly that measured transversely, since erythema is not used in any other country than Japan.

Comparative sequences of two type 1 dengue virus strains possessing different growth characteristics in vitro.

The complete genome sequences of two dengue-1 virus strains having different growth characteristics (Mochizuki and A88) were compared with other published strains. The sequence analysis indicated several unique amino acid changes throughout the coding region of Mochizuki strain, mostly in envelope (E) protein. A unique amino acid, Ile-69 for Mochizuki strain at E protein resulted in the loss of an Asn-67-linked glycosylation site. A Thr substitution for Ala-114 at C protein and amino acid changes found in E, non-structural NS3, NS4a, and NS5 proteins were unique for A88 strain. These substitutions might be correlated to their different growth characteristics in vitro.

Changes in the incidence and etiological patterns of bacteremia associated with acute leukemia over a 25-year period.

During the 25-year period from 1972-1996, 360 episodes of bacteremia occurred in 248 (45%) of a total of 548 patients with acute leukemia on our hematology ward, with the rate of occurrence remaining almost unchanged. Patients with acute nonlymphocytic leukemia, however, had a significant decrease in the incidence of bacteremia during the last 5-year period. Gram-negative bacilli decreased in relative frequency from 64% for the first 15-year period to 40% for the last 5-year period, whereas gram-positive cocci increased from 24% to 51%. Escherichia coli and Enterobacter cloacae somewhat decreased in frequency, whereas coagulase-negative staphylococci and streptococci had considerable increases. In contrast, Pseudomonas aeruginosa was isolated at a relatively constant frequency, forming one of the top two pathogens throughout the study period. Despite the shift toward gram-positive cocci, therefore, P. aeruginosa remains a key organism in considering the initial empiric antibiotic regimen and infection prevention during neutropenia.

Aeromonas bacteremia in patients with hematologic diseases.

Over a 23-year period, 17 patients with hematologic diseases developed Aeromonas bacteremia while in our hematology ward. Male predominance (14 patients, 82%) was seen, with a predilection for the elderly. Hematologic malignancies, especially acute leukemia, accounted for 15 (88%) of all patients. Cancer chemotherapy and neutropenia (15 patients each) were the most common preceding host conditions. Aeromonas bacteremia generally occurred in the second half of the year (July-December), with no exposure to water or fish. Seven recent isolates comprised Aeromonas sobria (five isolates) and Aeromonas hydrophila (two isolates). Twelve patients (71%) showed a clinical picture ranging from mild gastroenteritis to severe enterocolitis. Anorectal and hepatobiliary infections were also noted in a few patients. The overall mortality rate was 35%. Ten (77%) of the 13 patients who were treated with aminoglycoside plus cephalosporin or carbapenem survived in association with marrow recovery.

Pulmonary mucormycosis in a hematology ward.

During a 24-year period, seven patients with leukemia undergoing cytotoxic or immunosuppressive therapy developed pulmonary mucormycosis in our hematology ward. The autopsy incidence in patients with acute leukemia was 2.1%, with no significant rise during the last decade. Most cases occurred in early autumn. Two patients diagnosed premortem were successfully treated with antifungal drugs, whereas five patients diagnosed postmortem died within three weeks following radiographic identification. Persistent fever despite antibiotic coverage was the first clinical presentation, followed mostly by the radiographic appearance of rounded densities, subsequently progressing to hemorrhagic infarction with hemoptysis and/or pleuritic pain. Crescentic cavitation developed when hematologic remission was achieved. Thus, certain radiographic patterns with or without pulmonary infarct syndrome in the proper clinical setting should arouse suspicion of mucormycosis, providing the opportunity for early diagnosis and adequate treatment.

Rhabdomyolysis complicating polymicrobial sepsis in a patient with acute leukemia.

Rhabdomyolysis with myoglobinuria is an uncommon complication of sepsis, whether monomicrobial or polymicrobial, even in its severe form. We describe a middle-aged woman with acute leukemia who developed rhabdomyolysis and myoglobinuria during the fatal course of chemotherapy-induced sepsis due to Bacteroides thetaiotaomicron and Enterococcus faecalis, followed by multiple organ dysfunction syndrome. In addition, autopsy revealed disseminated infections with Aspergillus and Candida. None of these organisms has been reported to be involved in the pathogenesis of rhabdomyolysis. Therefore, the etiology of the rhabdomyolysis in this case was probably multifactorial, with polymicrobial septic processes being possibly important contributing factors.

Bacteremia caused by the Bacteroides fragilis group in patients with hematologic diseases.

During a 22-year period, 13 patients with hematologic diseases developed bacteremia caused by the Bacteroides fragilis group, with a frequency which remained almost unchanged. Nine patients (69%) had polymicrobial infections. Acute leukemia was the most common underlying disease. The lower intestinal tract (necrotizing enterocolitis and anorectal abscesses) was the most common source of infection. Prior antibiotic therapy was the most frequent host condition before bacteremia, followed by cancer chemotherapy, neutropenia, thrombocytopenia and hypoproteinemia. Septic shock occurred only in seven patients with polymicrobial infections. Six patients, including five with shock, died within a week of onset, while the other seven survived for at least three weeks. Despite its clinical similarity to aerobic gram-negative infection, bacteremia due to the B. fragilis group may well, therefore, be suspected particularly when neutropenic patients who present with lower intestinal symptomatology develop a persistent fever unresponsive to the initial empiric antibiotic therapy.

Jaundice associated with Pseudomonas aeruginosa bacteremia complicating acute leukemia.

Two adult patients with acute leukemia developed marked jaundice during Pseudomonas aeruginosa bacteremia. The progressive increase in serum conjugated bilirubin levels was disproportionate to the gradual decrease in serum alkaline phosphatase and transaminase activity to or below low normal. The production of coagulation factors decreased. Autopsy revealed periportal cholestasis with minimal liver-cell damage. These findings suggested decreased metabolic activity of liver cells associated with bacteremia, probably leading to impaired bilirubin excretion. Both patients died despite appropriate antibiotic therapy. Isolated hyperbilirubinemia, thus, seemed to be an ominous prognostic sign in severe infection.

Capnocytophaga sputigena bacteremia associated with acute leukemia.

During a three-year period, Capnocytophaga sputigena bacteremia occurred in three patients with acute leukemia receiving induction therapy on a hematology ward. Oral pathology such as periodontitis or severe mucositis was considered to be the most likely source of bacteremia. All three blood culture isolates were identified as that species by deoxyribonucleic acid (DNA) homology studies. Because of the phenotypical similarity of Capnocytophaga species, it is difficult to differentiate them by conventional bacteriological methods. All three isolates were susceptible to antibiotics active against most anaerobes. However, production of beta-lactamase was found in two isolates, one of which proved resistant to both piperacillin and ceftazidime. Therefore, the empiric use of imipenem or clindamycin may be justified in febrile granulocytopenic patients with cancer who develop significant oral lesions.

Staphylococcus aureus bacteremia in patients with hematologic disorders.

During the 20-year period, 1972-1991, 27 episodes of Staphylococcus aureus bacteremia, including 10 with methicillin-resistant strains (MRSA), were documented in 26 patients with hematologic disorders, mainly acute leukemia and malignant lymphoma, representing 6% of all 433 episodes of bacteremia in a hematology unit. MRSA replaced methicillin-sensitive strains (MSSA) in the last four years. The skin and upper respiratory tract were the two most common primary foci. Most episodes occurred during neutropenia. Pharyngeal colonization often preceded the development of bacteremia. Antibiotic therapy predisposed to MRSA acquisition during hospitalization, whereas MSSA was mostly detected in admission cultures. Among 22 patients with monomicrobial bacteremia, 19 (86%) survived longer than one week, including all four with MRSA bacteremia who received vancomycin. The survival rate did not differ materially between MRSA and MSSA bacteremias. Secondary foci, chiefly located in the lung, were found in 30% of all patients with S. aureus bacteremia. Prolonged antibiotic therapy, therefore, seems warranted in patients with evident metastatic lesions, although abbreviated therapy is proposed in neutropenic cancer patients.

Changing patterns of blood culture isolates from patients with acute leukemia: a review of twenty years' experience.

During the 20-year period, 1972-1991, 286 episodes of bacteremia occurred in 200 (45%) of 445 patients with acute leukemia in a hematology ward, giving an incidence of 482 episodes per 1,000 hospital admissions. The frequency of bacteremia was almost unchanged throughout the study period. The frequency of gram-negative bacilli decreased significantly, however, from 81% of all the isolates for the first half of the study period to 50% for the latter half. Despite the common use of ceftazidime and imipenem during the last 5-year period, Pseudomonas aeruginosa increased in frequency to be the most frequent organism. This was opposite to the decreased frequencies of Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. The isolates of P. aeruginosa obtained during this period, all of which proved sensitive to ceftazidime and/or imipenem, were almost equally distributed among five serogroups, although a temporal preponderance of a limited number of serogroups was observed during the preceding 15-year period. On the other hand, the frequency of gram-positive cocci increased from 9% in the first decade to 35% in the latter decade. Staphylococcus epidermidis, Enterococcus species and, to a lesser extent, Staphylococcus aureus were ranked as major pathogens. Among the recent isolates of S. aureus, methicillin-resistant strains virtually replaced methicillin-sensitive ones. Therefore, until more effective means for control of P. aeruginosa bacteremia in particular become available, the occurrence of this infection will continue to limit the successful treatment of acute leukemia.

[Bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA)].

Bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) is most likely to occur in compromised patients with prolonged hospitalization who are receiving antibiotics, particularly beta-lactam ones. The clinical picture of MRSA bacteremia is almost the same as that of bacteremia due to methicillin-sensitive S. aureus. There seems to be no significant difference in prognosis between the two types of staphylococcal bacteremia when patients in the same disease category are considered. Vancomycin is at present the only antibiotic for the treatment of MRSA bacteremia. It is therefore important to use the drug adequately so as to prevent its adverse effects and delay the appearance of resistant organisms.