Systemic Haemophilus influenzae disease: an overview.
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Biomedical subjects
Publications and source records attributed to A S Dajani.
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Intravenous TMP-SMZ was used to treat 19 infectious episodes in 18 patients ranging in age from 3 weeks to 13 years. Thirteen patients with various soft tissue or skeletal infections caused by Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus. Streptococcus pyogenes, or Acinetobacter anitratus were successfully treated. Three children with four episodes of CSF shunt infections due to coagulase-negative staphylococci were treated successfully also. The only treatment failures were in two newborn infants with enteric gram-negative bacterial ventriculitis. TMP-SMZ was given at a daily dose of 10 and 50 mg/kg, respectively, every six hours. The drug was administered intravenously for a mean duration of 10 days (range 4 to 32); in 11 patients this was followed by oral administration for a mean of nine days (range 2 to 18). Half-life of TMP after intravenous administration was 5 1/4 hours; that of SMA was 8 1/2 hours. Levels determined three to four days after starting therapy were generally higher than levels obtained at corresponding times after the first dose. CSF/blood TMP and SMA ratios, determined in four patients, were 0.6 and 0.5, respectively. Side effects were observed in 14 patients, and neutropenia was the most common adverse reaction. Intravenous TMP-SMZ is an effective antimicrobic agent in the treatment of infections due to susceptible organisms. The frequent side effects, although reversible and of no major clinical consequence, suggest that future use of TMP-SMZ should be monitored closely.
Viridin B, a bacteriocin produced by Streptococcus mitis, copurified with the alpha-hemolysin after ammonium sulfate precipitation and gel filtration on Sephadex G-200. The bacteriocin and hemolysin were separated in some instances by ion-exchange chromatography on diethylaminoethyl-Sephadex A-50, but the two substances were shown to be distinct after polyacrylamide gel electrophoresis. Attempts at recovery of nonhemolytic or nonbacteriocinogenic mutants were unsuccessful after exposure to mutagenic agents. The molecular weight of viridin B was determined to be approximately 87,000.
Soluble antigens of Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis, and group B streptococcus were looked for in cerebrospinal fluid, serum, and urine by using the staphylococcal coagglutination test, latex agglutination test, and counterimmunoelectrophoresis. The staphylococcal coaggultination and latex agglutination tests were more sensitive than counterimmunoelectrophoresis in identifying antigens of H. influenzae type b, S. pneumoniae, and N. meningitidis. None of the three tests successfully detected group B streptococcal antigens in body fluids. Nonspecific reactions noted with the staphylococcal coagglutination test could be usually eliminated after premixing test specimens with soluble protein A.
Colonization of prepubertal boys and girls with group B streptococci was studied prosepctively for one year. Throat, anal canal, and vaginal cultures were obtained from 415 children not receiving antimicrobics. The over-all colonization rate at any site was 11.3% and did not vary with age, sex, or season. Streptococci were recovered most commonly from the anal canal. Throat colonization was comparable in boys and girls. A total of 71 sites were positive for the organism in the 47 colonized children. Serotype Ia was the most common (41% of isolates). Types II and III accounted for 24% and 20%, respectively. Colonization at more than one site occurred in 20 children and in two of these children, different serotypes were recovered from different sites.
Yersinia enterocolitica systemic infections are uncommon and osteomyelitis due to this organism is very rare. We report a 9-year-old girl with thalassemia major, liver cirrhosis, and hemosiderosis who developed osteomyelitis of the rib caused by Y enterocolitica type 0:3. Serologic response to the infection was confirmed. No definite source of infection was identified.
Two infants had pneumococcal pneumonia and bacteremia, complicated by pneumatocele formation. The pneumatoceles appeared during the recovery phase and were indistinguishable from those associated with staphylococcal pneumonia. Complete resolution occurred in both patients. Pneumatoceles occur in pneumonias caused by varied agents; therefore, determination of the cause is imperative for appropriate therapy.
Using positive blood, lung, or pleural fluid cultures as definitive criteria for bacterial infection, 43 examples of Hemophilus influenzae type b pneumonia were identified in a 43-month period. The mean age of the patients was 26 months; 12% were older than 5 years of age. Associated infections were found in 34 patients and included upper respiratory infections, otitis media, epiglottitis, and meningitis. Positive nasopharyngeal cultures were observed in only 33%. Radiologically, segmental or lobar infiltrates accounted for 85% of the pneumonias. In two cases, death was attributed to the pneumonia alone. Treatment with penicillin G or ampicillin was equally effective. Our data suggest that H. influenzae pneumonia is commonly a serious infection that cannot be distinguished clinically or radiologically from other pneumonias.
Viridin B, a bacteriocin produced by Streptococcus mitis (mitior), is bactericidal to Neisseria sicca. Oxygen consumption by actively growing N. sicca cultures ceased immediately upon exposure to viridin B. Adenosine triphosphate production was slightly enhanced within 1 h of exposure to the bacteriocin but was subsequently repressed. The uptake and incorporation of glucose was prevented in the presence of viridin B. The bacteriocin also blocked uptake of an amino acid mixture in chloramphenicol-pretreated cells. Pretreatment or concomitant treatment with a variety of antibiotics known to inhibit specific synthetic pathways did not alter the inhibition of macromolecular synthesis produced by the bacteriocin. Although viridin B blocks protein and nucleic acid syntheses, no degradation of such macromolecules was observed. The inhibitory effects of viridin B on macromolecular synthesis and on viability required the presence of sufficient nutrients to allow active metabolism of N. sicca. The bacteriocin did not inhibit viability or macromolecular synthesis in anaerobically incubated N. sicca. Thus, active, oxidative metabolism by N. sicca cells is essential for viridin B action. A model for viridin B action is proposed.
Several body fluids and various substances were examined for their effects on the action of viridin B, a Streptococcus mitis bacteriocin. Heme has been shown previously to interfere with viridin B action. In the present study, peroxidase and catalase, but not superoxide dismutase, interfered with the bacteriocin. Sulfhydryl-containing compounds had no effect. Trypsin, protease, and amylase exhibited interfering capacities. Of various body fluids tested, serum, saliva, and leukocyte lysate interfered with viridin B. The activity in leukocyte lysate was probably due to myeloperoxidase. Salivary activity was likely due to both peroxidase and amylase. Interfering activity in serum was neither complement dependent nor antibody mediated and was probably due to a combination of enzymatic activities. Temporal studies with these agents suggested more than one mechanism of interference with viridin B.
Two patients with periobital cellulitis, one of whom also had buccal cellulitis, had violaceous discoloration of the skin. Blood cultures from both patients yielded Streptococcus pneumoniae. Therefore, pneumococci should be considered, in addition to Haemophilus influenzae, as possible causes of cellulitis with violaceous or bluish-red discoloration.
Protein A-rich staphylococci coated with Haemophilus influenzae type b antiserum agglutinate specifically with homologous bacterial cells or with cell-free supernatant fluids of cultures of the organism. Antibody-coated staphylococci were used to detect soluble antigens in body fluids of patients infected with H. influenzae type b. Cerebrospinal fluid from 36 cases of meningitis caused by this orgainsm showed positive coagglutination tests in 86% of patients prior to initiation of therapy. Antigens could be detected in 46% of sterile cerebrospinal fluid specimens obtained from the same cases 1 to 10 days after therapy. Soluble antigens were also detectable in sera (58%) and urine specimens (67%) of patients with H. influenzae type b septicemia, when such specimens were tested within 10 days of onset of illness. No antigen could be detected in body fluids beyond 10 days. The coagglutination test was positive in 57% of all body fluids examined; contercurrent immunoelectrophoresis (CCIE) was positive in only 27%. All specimens positive by CCIE were also positive by coagglutination. No false-positive reactions were noted by either test in body fluids from controls. The coagglutination test is simple, specific, and more sensitive than the CCIE method and could be a valuable tool for detecting antigens in body fluids of patients with various infections.
Two separate outbreaks due to Flavobacterium meningosepticum type E occurred in a neonatal intensive care unit in March-April and July 1975. The first outbreak involved all five infants in the unit. Two infants developed meningitis, one had bacteremia, and two were colonized. During the second outbreak, five of seven infants were colonized but none developed disease. The upper respiratory tract was colonized first in most instances, and the organism persisted at this site for a mean of 17.3 days. Duration of colonization was more prolonged in infants receiving antibiotics than in untreated infants. Extensive environmental surveillance failed to demonstrate a reservoir, however, F. meningosepticum was recovered from three nasoendotracheal tubes and from an aerosol tube before colonization of four infants. The organism was resistant to most antimicrobial colonization of four infants. The organism was resistant to most antimicrobial agents tested and developed resistance to others during the treatment course of one infant. Although F. meningosepticum was not recovered from cultures of transport vehicles, several other gram-negative bacteria were isolated and were also resistant to multiple antibiotics.
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Single-dose antibiotic therapy was evaluated in 108 episodes of culture-confirmed, uncomplicated gonorrhea in 100 prepubertal children. There were 15 boys and 85 girls between 14 months and 14 years of age. Penicillin G procaine, 100,000 units/kg intramuscularly, was compared with amoxicillin trihydrate, 50 mg/kg orally. Probenecid, 25 mg/kg, was given simultaneously. Both drugs provided prompt bacteriological and clinical response. Multiple episodes of gonorrhea, presumably caused by reexposure, occurred in six girls. Oral and anal cultures were negative in all of 47 Costa Rican cases but were commonly positive in US children. Anal cultures yielded gonococci in 52% of girls and 25% of boys, and oral cultures were positive in 18% and 13%, respectively. In three instances, rectal cultures confirmed the diagnosis when vaginal cultures were negative. Gonorrhea should be considered in every child with vaginal or urethral discharge. Single-dose penicillin-probenecid or amoxicillin-probenecid treatment is curative.
Bacteriocin-like activities were detected in 78% of 120 alpha-hemolytic streptococcal isolates. Inhibitory substances from three such isolates (one Streptococcus sanguis strain and two S. mitis strains) were investigated further and termed viridins (A, B, and C). The viridins were unique among bacteriocins of gram-positive bacteria in that they inhibited many gram-negative bacteria in addition to inhibition of a variety of gram-positive organisms. Viridins were obtained in a cell-free state only after mechanical disruption of bacteriocinogenic cells but could not be isolated from supernatant fluids of cultures of such bacteria or from freeze-thaw liquor of agar on which the bacteria had been grown. Viridin B could be partially purified by ammonium sulfate precipitation and by gel filtration on a Sephadex G-100 column. This bacteriocin had some unusual properties including heat lability, a narrow pH range of activity, and lack of adsorptive capacity to susceptible bacteria. Although viridin B was bactericidal to a Neisseria sicca strain, it was only bacteriostatic against a coagulase-negative staphylococcus.
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Viridin B, a bacteriocin produced by Streptococcus mitis strain 42885, was shown previously to exert a bactericidal effect against a Neisseria sicca strain but only a bacteriostatic effect against a coagulase-negative staphylococcus. In the present report, this dual effect was defined further. Viridin B caused the appearance of mesosomes in both indicator strains early in the course of exposure. Whereas mesosomes were the only noticeable alterations in the staphylococcal strain at all times of exposure to bacteriocin, progressive changes occurred in the N. sicca cells involving the nucleoid and cytoplasmic contents and resulting in the appearance of bacterial ghosts. Biochemical studies indicated a rapid and complete cessation of the incorporation of [3H]thymidine in N. sicca and in the staphylococcus. Whereas the incorporation of [3H]leucine and [3H]uridine in N. sicca was completely stopped, such incorporation was only reduced in the staphylococcus.