Determination of serum gentamicin sulfate levels: ordering patterns and use as a guide to therapy.

Determination of serum gentamicin levels (SGLs) is helpful in monitoring therapy in patients receiving this drug because there is a narrow therapeutic margin and serum levels may vary greatly between patients receiving similar doses. During a ten-month period, definite indications for obtaining SGL determinations were present for 189 of 212 serum samples (89.2%) submitted to the laboratory. However, 110 samples (51.9%) were improperly drawn and results of 85 samples (40.1%) were ignored. Only 26 of the 62 correctly drawn and not ignored samples (41.9%) were appropriately acted on. At most, 42 of the 212 samples (19.8%) were appropriately used in making patient-care decisions. Thus, in this study, an inordinatley large number of SGLs were incorrectly drawn, apparently ignored, or inappropriately used in making patient-care decisions.

Zygomycosis of the maxillary sinus and palate caused by Basidiobolus haptosporus.

Basidiobolus haptosporus is known to cause subcutaneous zygomycosis in tropical Africa and Asia. We cared for a 49-year-old hyperglycemic, asplenic man who had never traveled outside the United States and who was seen initially for a painless palatal ulcer with cutaneous hypesthesia of the right cheek and upper lip. An invasive process involved the right middle nasal turbinate, maxillary antrum, maxillary division of the trigeminal nerve, and bony palate. Histological examination of biopsy tissue showed necrotizing granulomata with broad, nonseptate hyphae. Basidiobolus haptosporus was cultured from this tissue. Various laboratory studies revealed no immunologic defect and his lesions responded to therapy with amphotericin B. To our knowledge, this represents the first case of zygomycosis caused by B haptosporus in the Americas and the first culture-documented case of invasive mycosis caused by this mold.

Pseudobacteremia caused by Clostridium sordellii.

Thirteen of 280 (4.6%) blood cultures collected over a 12-day period were positive for Clostridium sordellii, a spore-forming anaerobe, rarely considered a human pathogen. Nosocomial bacteremia and intrinsic contamination of material used to culture blood were excluded as the source of the organism. Contaminated tincture of thimerosal used to swab the rubber stoppers of blood culture bottles prior to venting (aerobic) or during blind subculturing after 24 hours of incubation (anaerobic) in the clinical microbiology laboratory was determined to be the cause of the pseudobacteremia. After appropriate safe-guards were implemented, we have continued to use tincture of thimerosal for these procedures with no further growth of C sordellii from blood cultures. The importance of less-conspicuous steps in the routine processing of culture material have been reemphasized.

Actions of tacrine and galanthamine on histamine-N-methyltransferase.

Histamine-synthesizing neurons in the brain may play an important role in cognition, and a histaminergic deficit has been found in Alzheimer's disease (AD). The AD medication tacrine was previously shown to inhibit some forms of rodent histamine-N-methyltransferase (HNMT), but the effects of AD drugs have not been investigated on human HNMT activity. Presently, the effects of tacrine and galanthamine (another AD medication) were studied on the activity of several forms of human and rat HNMT. Tacrine (0.01-10 microM) inhibited both human and rat HNMT activity in a concentration-dependent manner, but was less potent on both human embryonic kidney and recombinant human brain HNMT than on rat kidney HNMT (IC50 values were 0.46 and 0.70 microM vs. 0.29 microM, respectively). Galanthamine (up to 10 microM) did not influence the activity of rat kidney or human HNMT. Tacrine, but not galanthamine, may achieve brain levels sufficient to influence histamine metabolism in some patients treated for AD.

Infective endocarditis of a bicuspid aortic valve caused by Hansenula anomala.

Infective endocarditis due to Hansenula anomala developed on a bicuspid aortic valve in a 40-year-old man. H. anomala, an ascomycetous yeast, may be a member of the normal flora of the throat and alimentary tract in humans but has not been previously known to be pathogenic in humans. A past history of intravenous drug use may have contributed to the development of disease in this patient.

Characteristics of coagulase-negative staphylococci from infants with bacteremia.

Twenty-nine infants were identified as having coagulase-negative staphylococcal (C-S) bacteremia. Fourteen infants had pneumonia and 10 had central line-associated bacteremia. Twenty-four of 29 (83%) had invasion of the mucocutaneous barrier at the time the positive blood culture was drawn. Clinical signs and symptoms were nonspecific. Apnea/bradycardia was the most prevalent clinical feature, occurring in 20 (69%) infants. Staphylococcus epidermidis was the most frequent blood culture isolate, occurring in 21 (72%) cases. Slime production by C-S blood culture isolates occurred in 23 (79%) cases. There was no prevalent antibiotic resistance pattern, phage type or plasmid profile among blood culture isolates from infants with bacteremia. Mucocutaneous isolates of C-S from infants with bacteremia were compared with those from infants without invasive disease. Infants with bacteremia had a significantly higher percentage of slime-producing organisms (75% vs. 58%, P = 0.027) and a significantly higher percentage of S. epidermidis species (79% vs. 53%, P = 0.001) than isolates from infants without bacteremia. Our data support the relationship of slime production and the S. epidermidis species of C-S as virulence factors in infants with foreign bodies. Testing C-S for slime production is a relatively simple laboratory procedure which may be an additional aid in the evaluation of their clinical significance.

Clinical significance of serotype, biotype, and beta-lactamase production of respiratory isolates of Hemophilus influenzae.

The correlation between clinical significance and serotype, biotype, and beta-lactamase production of 101 respiratory isolates of Hemophilus influenza from nonbacteremic patients was determined. Six of 33 (18.2%) isolates from patients with definite or probable infection were serotypable; only two of 67 (3%) isolates from colonized patients were serotypable. Eight-seven and one-half per cent of the serotypable strains were biotypes I or IV; 78.8% of nonserotypable strains were biotypes II, III, or V. Biotype distribution among isolates from patients with definite or probable infection were similar to isolates from colonized patients. beta-lactamase production was not helpful in evaluating clinical significance. Nonserotypable H. influenzae is an important cause of nonbacteremic pneumonia in elderly men.

Clinical significance of citrobacter isolates.

Little is know about the clinical significance of isolating Citrobacter in the clinical laboratory. During a one-year period, 116 Citrobacter isolates were obtained from 77 patients with 83 suspected infectious episodes. The majority of the suspected infectious episodes involved the urinary tract (45%) or respiratory tract (41%). Citrobacter diversus was associated with 42% of the episodes, Citrobacter freundii with 29%, and Citrobacter species with 29%. In 42% of the suspected infectious episodes, the presence of Citrobacter was considered clinically significant; in the others, the significance of the Citrobacter isolates was indeterminate or considered to be commensal. Two thirds of the significant infections were hospital-acquired. Most patients (73%) from whom Citrobacter was cultured had underlying diseases or factors predisposing to infection. These data suggest that Citrobacter is a cause of significant opportunistic nosocomial infection in the hospital.

Community-acquired bacteremic Achromobacter xylosoxidans type IIIa pneumonia in a patient with idiopathic IgM deficiency.

A man was hospitalized with bacteremic Achromobacter xylosoxidans type IIIa pneumonia. The authors are aware of no previously reported similar infections caused by this bacterium. A clinical cure was achieved with a combination of carbenicillin and kanamycin therapy. Microtiter susceptibility testing revealed that carbenicillin was the antibiotic to which A. xylosoxidans IIIa was most sensitive (minimal inhibitory concentration, 1.6 microgram/ml) and that synergy between carbenicillin and kanamycin existed. During the patient's hospitalization, deficiency of IgM (21 mg/dl) was found. Specific serum activity against A. xylosoxidans IIIa was detected by the agglutination method. Specific anti-A. xylosoxidans IIIa IgG, but not IgM, was detected by indirect immunofluorescence. It appears that a defect in immunologic recognition of A. xylosoxidans IIIa as an invasive bacterium, a defect in synthesis of specific IgM, or both, contributed to this patient's infection.

A third life for burimamide. Discovery and characterization of a novel class of non-opioid analgesics derived from histamine antagonists.

Burimamide, a histamine (HA) derivative with both H2- and H3-blocking properties, induces antinociception when injected into the rodent CNS. Several related compounds share this property, and structure-activity studies have shown that this new class of analgesics is distinct from known HA antagonists. The prototype, named improgan, shows a preclinical profile of a highly effective analgesic, with activity against thermal, mechanical and inflammatory nociception after doses that do not alter motor balance or locomotor activity. Improgen analgesia is not blocked by opioid antagonists and is observed in opioid receptor knock-out mice. Unlike morphine, improgan does not induce tolerance after daily dosing. Extensive in vitro pharmacology studies have excluded known histaminergic, opioid, serotonergic, GABAergic and adrenergic receptor mechanisms, as well as 50 other sites of action. The improgan-like analgesic activity of some HA congeners suggests an analgesic action on a novel HA receptor, but further studies are required to substantiate this. Studies in progress are characterizing the sites and mechanisms of action of improgan, and developing brain-penetrating derivatives that could be useful for clinical pain.

Evaluation of coagulase-negative staphylococcal isolates from serial nasopharyngeal cultures of premature infants.

The present study was undertaken to determine whether very low birth weight infants in a neonatal intensive care unit became colonized with virulent strains of coagulase-negative staphylococci (C-S) over time (i.e., those characterized as Staphylococcus epidermidis, slime positive, and/or multiply antibiotic resistant), and if so, whether the initial colonizing strains developed these characteristics or whether the strains themselves changed. Nasopharyngeal (NP) cultures were obtained weekly on 28 very low birth weight (less than 1750 g) infants hospitalized for a mean of 8 wk (range 4-15 wk). There were 105 isolates of C-S recovered from 96 cultures that were characterized by species, biotype, antibiotic susceptibility pattern, and slime production (screening parameters). Isolates from the same infant with highly similar screening parameters then underwent phage typing and plasmid analysis to increase the likelihood of establishing strain identity. C-S colonization rose from 12% on admission to 75% by wk 2, then gradually declined to 30% by wk 6 and remained stable through wk 10. There were no significant differences among C-S isolates from wk 1 compared with wk 10 of hospital stay with respect to distribution of species, slime positive, or multiply antibiotic resistant strains. One biotype of S. epidermidis was recovered from 46% of study infants, but only one infant was colonized with a predominant biotype of S. epidermidis throughout hospitalization. Thirteen pairs of isolates recovered from 12 of the infants on two or more wk were found to be identical by phage typing and plasmid analysis. Only seven of these 13 pairs of isolates had concordant results for all the screening parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Acremonium kiliense osteomyelitis of the calvarium.

A 35-year-old man with osteomyelitis of the calvarium, from which Acremonium kiliense was consistently isolated, was successfully treated with amphotericin-B and ketoconazole in addition to craniectomy. Subsequent acrylic cranioplasty produced a good cosmetic result.

Group B streptococcal infections in adult males.

A 19-month study of group B streptococcal infection was performed to investigate the spectrum of such infections in adult males, the relation of serotypes to clinical illnesses, the effects of previous antibiotic therapy on infection and colonization, and the antibiotic susceptibility pattern of these organisms. Twenty-four patients had definite or possible infections while 41 patients were colonized with group B streptococci. The most frequent infections encountered were pneumonia (ten cases) and soft tissue infections (nine cases). Five infections (21%) were nosocomial in origin. The most frequent serotypes were Ia and II. No correlation of serotype and type of infection was observed. Patients receiving previous antibiotic therapy were significantly more likely to be colonized than infected with group B streptococci. Penicillin was the antibiotic to which these organisms were most susceptible; tetracycline and gentamicin showed the least activity.

Hemophilus influenzae type F pneumonia in adults.

A 69-year-old man was hospitalized with fatal bacteremic Hemophilus influenzae type F pneumonia. Three cases of type F pneumonia have been reported previously. When compared with 22 reported cases of bacteremic type B pneumonia, patients with type F infection were more likely to be elderly males who succumbed to their infection (p less than 0.05). Statistically significant differences in the incidence of underlying conditions or in the extent of pneumonia were not present.

Case report. Disseminated sporotrichosis presenting as sarcoidosis: electron microscopic and immunologic studies.

A 50-year-old black man with constitutional symptoms, cutaneous nodules, and bilateral hilar adenopathy was found to have non-caseating granulomata on bronchial biopsy. He was treated with corticosteroids for sarcoidosis. Within five months he was found to have disseminated sporotrichosis. Electron microscopy revealed mycelial forms of S. schenckii in superficial lesions and yeast forms from deep tissue sites: no novel forms were seen. Blood mononuclear cell studies revealed hyperactive suppressor cells with respect to non-specific T cell targets and the antigen specific target. Examination of the initial biopsy material after digestion with diastase before PAS staining revealed budding yeast consistent with S. schenckii. This case emphasizes the need for careful histopathologic examination of clinical material before a diagnosis of sarcoidosis is made, and reveals an immunologic abnormality which may account for the patient's anergic state and susceptibility to S. schenckii infection.

Pulmonary aspergillosis and the importance of oxalate crystal recognition in cytology specimens.

A 62-year-old man, previously healthy but alcoholic, and who was clinically thought to have bacterial pneumonia, presented with a pulmonary infiltrate in the right apex, and suddenly died of exsanguinating hemoptysis. Sputum cultures yielded Aspergillus niger and Candida krusei while sputum cytology revealed numerous birefringent crystals in a background of acute inflammatory exudate. Autopsy findings showed invasive aspergillosis with a large mycetoma-containing cavity in the lung that was associated with localized massive oxalosis. This case further substantiates the fact that the presence of calcium oxalate crystals in pulmonary biopsy and cytology specimens can be regarded as an important diagnostic aid in the diagnosis of pulmonary aspergillosis due to A niger.

Colonization with slime-positive coagulase-negative staphylococci as a risk factor for invasive coagulase-negative staphylococci infections in neonates.

Mucocutaneous cultures obtained at admission and subsequent weekly nasopharyngeal cultures were obtained on 182 infants in the neonatal intensive care unit (NICU) over 3 months to assess whether a relationship existed between colonization with coagulase-negative staphylococci and invasive infection, particularly with respect to slime production. Nasopharyngeal colonization by coagulase-negative staphylococci occurred in a mean of 58% of infants weekly, with an equal prevalence of slime-positive and slime-negative isolates over time. Colonization of the nasopharynx on admission increased from 8.9% of those admitted within the first day of life to 33% of those admitted thereafter (p less than 0.005). The presence of slime-positive coagulase-negative staphylococci on admission was not predictive of later patterns of colonization with respect to slime. Of infants not colonized on admission who had subsequent cultures, 72% became colonized with coagulase-negative staphylococci that were equally likely to be slime-positive or slime-negative. The incidence of invasive infections was 4.4%. Infants with slime-positive mucocutaneous colonization were more likely to develop invasive coagulase-negative staphylococci disease than infants with slime-negative or no colonization (8.4% versus 1.1%; p less than 0.025). The incidence of slime-positive coagulase-negative staphylococci isolates from blood cultures was 6/7 (86%) whereas those from mucocutaneous cultures was 131/260 (50%) (p = 0.06). Colonization with slime-positive coagulase-negative staphylococci is a significant risk factor for developing invasive coagulase-negative staphylococci disease and these organisms are responsible for the majority of coagulase-negative staphylococci invasive infections.

Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats.

Within the past 2 years, a putative causal relationship has been reported between vaccination against rabies and the development of fibrosarcomas at injection sites in cats. A retrospective study was undertaken, involving 345 cats with fibrosarcomas diagnosed between January 1991 and May 1992, to assess the causal hypothesis. Cats with fibrosarcomas developing at body locations where vaccines are typically administered (n = 185) were compared with controls (n = 160) having fibrosarcomas at locations not typically used for vaccination. In cats receiving FeLV vaccination within 2 years of tumorigenesis, the time between vaccination and tumor development was significantly (P = 0.005) shorter for tumors developing at sites where vaccines are typically administered than for tumors at other sites. Univariate analysis, adjusted for age, revealed associations between FeLV vaccination (odds ratio [OR] = 2.82; 95% confidence interval [CI] = 1.54 to 5.15), rabies vaccination at the cervical/interscapular region (OR = 2.09; 95% CI = 1.01 to 4.31), and rabies vaccination at the femoral region (OR = 1.83; 95% CI = 0.65 to 5.10) with fibrosarcoma development at the vaccination site within 1 year of vaccination. Multivariate analysis, adjusted for age and other vaccines, also revealed increased risks after FeLV (OR = 5.49; 95% CI = 1.98 to 15.24) and rabies (OR = 1.99; 95% CI = 0.72 to 5.54) vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)