Haemophilus

J Antimicrob Chemother, 1990 Sep, 26(3), 371 - 80
Effect of low concentrations of clavulanic acid on the in-vitro activity of amoxycillin against beta-lactamase-producing Branhamella catarrhalis and Haemophilus influenzae; Cooper CE et al.; Concentrations of amoxycillin/clavulanic acid achievable in the respiratory tract following oral dosage were assessed for in-vitro activity against beta-lactamase-producing strains of Branhamella catarrhalis and Haemophilus influenzae . In agar-dilution studies, 8 mg amoxycillin/l was required to inhibit 45 strains of beta-lactamase-producing B . catarrhalis, whereas all the strains were inhibited by 0.5 mg amoxycillin/l in the presence of 0.01 mg clavulanic acid/l . Similarly, 0.1 mg amoxycillin plus 0.05 mg clavulanic acid/l were bactericidal against beta-lactamase-producing strain of B . catarrhalis and prevented regrowth within 24 h . In tests against 43 beta-lactamase-producing strains of H . influenzae, concentrations of up to 128 mg amoxycillin/l were required for inhibition, whereas 32 strains (75%) were fully sensitive to amoxycillin (MIC 0.5 mg/l) in the presence of 0.12 mg clavulanic acid/l . These concentrations of amoxycillin/clavulanic acid were also bactericidal for a beta-lactamase-producing strain of H . influenzae . The study therefore showed that amoxycillin/clavulanic acid, at concentrations similar to those likely to be achieved in the respiratory tract following oral dosage, was bactericidal in vitro for beta-lactamase-producing isolates of B.catarrhalis and H . influenzae.

J Infect Dis, 1990 Sep, 162(3), 659 - 63
Biochemical characterization and worldwide distribution of serologically distinct lipopolysaccharides of Haemophilus influenzae type b; van Alphen L et al.; The sugar composition and the electrophoretic mobility in SDS-polyacrylamide gel electrophoresis of the various lipopolysaccharides (LPS) from clinical isolates of Haemophilus influenzae type b (Hib) were determined to correlate epidemiologic data with compositional data . Rabbit sera specific in Ouchterlony immunodiffusion for 10 different LPS (LPS 1-10) reacted with 647 or 690 Hib strains isolated from patients with invasive disease in various continents . Serotype 1 was predominant and was found in 550 isolates (80%) . None of the Hib isolates reacted with antisera specific for LPS of two nonencapsulated isolates (LPS 5 and 6) . Sugar analysis by gas-liquid chromatography of trimethylsilylated methyl glycosides revealed that the LPS of the 10 serotypes contained glucose, galactose, L-glycero-D-mannoheptose, and glucosamine in various proportions . LPS 1, 2, 8, and 9 contained the highest amounts of glucose and galactose relative to L-glycero-D-mannoheptose, which is considered present in constant amounts in H . influenzae LPS . LPS 1, 2, and 9 were most frequently found in invasive disease isolates.

Infect Immun, 1990 Sep, 58(9), 2972 - 6
N-linked oligosaccharides of human transferrin are not required for binding to bacterial transferrin receptors; Padda JS et al.; Derivatives of human transferrin (hTf) with removed or modified N-linked oligosaccharides were compared with native hTf with respect to their binding to bacterial hTf receptors from Neisseria meningitidis, N . gonorrhoeae, and Haemophilus influenzae . Partially and fully deglycosylated hTf were prepared by enzymatic deglycosylation with glycopeptidase F and isolated by concanavalin A-Sepharose affinity chromatography . Oligosaccharide-modified hTf was prepared via mild periodate oxidation . Competition and direct binding experiments with the hTf derivatives demonstrated that the hTf oligosaccharides are not essential for binding to the bacterial hTf receptors.

Kitasato Arch Exp Med, 1990 Sep, 63(2-3), 131 - 6
Drug resistance plasmids of Actinobacillus (Haemophilus) pleuropneumoniae serotype 2 strains isolated from swine; Kawahara K et al.; Drug resistance plasmids were detected in two drug resistant strains of Actinobacillus (Haemophilus) pleuropneumoniae serotype 2 isolated in Japan . One strain, Hpn25, was resistant to ampicillin, kanamycin, streptomycin and sulfonamides, and harbored two plasmids with a molecular size of 3.7 and 4.1 kilobases (kb) . The other strain, Hpn18, which was resistant to streptomycin, tetracycline, and chloramphenicol, harbored three plasmids with a molecular size of 2.2, 12, and 35 kb . The resistance of Hpn 25 to streptomycin and sulfonamides is mediated by a 4.1 kb plasmid and that of Hpn 18 to streptomycin and chloramphenicol by one or more of the 2.2, 12, and 35 kb plasmids.

Hua Xi Yi Ke Da Xue Xue Bao, 1990 Sep, 21(4), 375 - 8
{Identification and typing of Actinobacillus actinomycetemcomitans by restriction endonuclease analysis}; Han A et al.; The aim of the present study was to investigate the potential of restriction endonuclease analysis (REA) for the identifying and typing of Actinobacillus actinomycetemcomitans (Aa) . Bacterial chromosomal DNA was extracted and digested with BamHI, HindIII, Sal I and Xho I respectively and separated by agarose gel electrophoresis . DNA fragment patterns of Aa and Haemophilus aphrophilus differed strikingly from each ether . The patterns of Aa FDC Y4 and Aa ATCC 29523, belonging to two different serotypes, also differed notably . Among the 4 enzymes used, Sal I and Xho I gave the most satisfactory results . The results of our work suggested that REA could be used to identify and type Aa . REA is stable, sensitive, accurate and reproducible . The method might be valuable in molecular epidemiologic studies on periodontopathic organisms.

Ugeskr Laeger, 1990 Aug 20, 152(34), 2420 - 2
{Purulent arthritis}; Riegels-Nielsen P et al.; At all ages, Staphylococcus aureus is the most common microorganism responsible for septic arthritis, but in children below five years of age Haemophilus influenzae is frequently found . In about 1/3 of the cases cultures are negative, primarily because of initiation of antibiotic therapy prior to sampling . A distended joint should be treated as infection until otherwise proved . Today repeated aspirations of the infected joint are recommended as initial treatment, if possible with additional joint lavage, together with systemic antibiotic therapy . In case with no clinical response within 2-4 days, surgical debridement of the joint with synovectomy is of utmost importance . Exercises without weight-bearing are initiated at an early stage and weight-bearing avoided for six weeks.

J Immunol Methods, 1990 Aug 7, 131(2), 195 - 202
Solid phase disruption of fluid phase equilibrium in affinity assays with ELISA; Hetherington S; Quantitation of antibody affinity for antigen can provide important information in assessment of the human immune response . Enzyme-linked immunosorbent assay (ELISA) methods are sufficiently sensitive to permit affinity measurements of low affinity, low titer antibody . The major assumption in using this method, that the solid phase does not influence the equilibrium of the fluid phase antibody-antigen interaction, is not strictly true . Hence, conditions must be chosen to minimize such interference, which can result in spuriously low values of affinity . The degree of solid phase interference was therefore quantitated for an ELISA that measures the affinity between antibody directed against the capsular polysaccharide of Haemophilus influenzae type b, using a monovalent 3-unit oligosaccharide prepared from polysaccharide . The solid phase antigen density had the greatest effect upon disruption of the fluid phase . The concentration of antibody chosen had a measurable but modest effect on the outcome of ELISA, whereas the time of incubation of the antibody and oligosaccharide had no demonstrable effect . By choosing the conditions of the assay carefully, it was possible to minimize interference from the solid phase, so that the measured affinity of anticapsular polysaccharide antibody for monovalent antigen was similar to that obtained with the more traditional precipitation method.

Lancet, 1990 Aug 4, 336(8710), 269 - 70
Effect of breast-feeding on antibody response to conjugate vaccine; Pabst HF et al.; Infants were immunised at the ages of 2, 4, and 6 months with conjugate Haemophilus influenzae type b vaccine, and their responses to the vaccine were evaluated by feeding method (breast or formula) . There were no significant differences between the groups in antibody levels at early ages . However the antibody levels were significantly higher in the breast-fed (57 infants) than the formula-fed group (24 infants) at 7 months (mean {SD} 29.8 {32.0} vs 17.5 {14.8} micrograms/ml) and at 12 months (55 vs 26 infants; 4.8 {4.4} vs 3.0 {2.3} micrograms/ml) . These findings are strong evidence that breast-feeding enhances the active immune response in the first year of life, and therefore the feeding method must be taken into account in the evaluation of vaccine studies in infants.

Zentralbl Veterinarmed B, 1990 Aug, 37(6), 430 - 5
{Examination of cattle with respiratory diseases for Mycoplasma and bacterial bronchopneumonia agents}; Binder A et al.; A total of 247 mycoplasma strains was isolated from 435 lungs, tracheobronchial secretions and nasal swabs originating from cattle with symptoms of bronchopneumonia . Mycoplasma (M.) bovis was found 89 times (36%) and was the most common mycoplasma species in the lungs . M . bovirhinis, M . bovigenitalium, M . spec . and Acholeplasma (A.) laidlawii were isolated 158 times (64%) . Among these mycoplasmas M . bovirhinis was the most widespread species (114 isolations) . In 55 cases (62%) M . bovis was associated with Pasteurella or Actinomyces (A.) pyogenes . The other mycoplasma species were found in 67 cases (42%) together with these bacteria . Without mycoplasmas Pasteurella and A . pyogenes occurred in 33 of the probes investigated (21%) . Beside mycoplasmas Haemophilus (H.) somnus was isolated from 16 of 162 tracheobronchial secretions investigated . The results confirm earlier suppositions that in most of the cases bronchopneumonia of cattle is a multifactorial event, frequently associated with mycoplasmas--especially M . bovis.

Wis Med J, 1990 Aug, 89(8), 461 - 3
Haemophilus influenzae B meningitis in a patient with a ventriculoperitoneal shunt and meningomyelocele; Brandstetter Y et al.; A child with an implanted ventriculoperitoneal (VP) shunt and meningomyelocele had an infection of his cerebrospinal fluid (CSF) . The organism cultured from the VP shunt apparatus and the meningomyelocele repair site was Haemophilus influenzae B (HIB), a very unusual pathogen in this setting . The patient was treated with the appropriate antibiotics, administered intravenously in accordance with accepted practice and available literature, with no improvement . The site of the persistent infection was finally determined to be within the meningomyelocele repair tissue . The patient's clinical status improved dramatically following the removal and replacement of the total shunt apparatus . The three-part apparatus tip was cultured according to the standard laboratory practice, but did not yield any organism . We conclude that the management of HIB meningitis in the presence of a VP shunt should include prompt removal of the apparatus . Recovery of the organism may be enhanced by separating the apparatus components and culture of the connections, instead of merely the indwelling tip.

J Pediatr Gastroenterol Nutr, 1990 Aug, 11(2), 201 - 4
Immunogenicity of Haemophilus influenzae type B vaccines in children with hepatoportoenterostomies; Rosenthal P et al.; To assess the immunogenicity of HIB vaccines in patients in whom hepatoportoenterostomies were performed for biliary atresia, eight such children received Haemophilus influenzae type b-polyribosylribitol phosphate (HIB-PRP) vaccine and had pre- and postvaccination total serum anti-PRP antibody concentrations determined by radioimmunoassay . Preimmunization anti-PRP antibody levels ranged from less than 0.125 to 0.40 microgram/ml {geometric mean antibody titer (GMT) 0.106 microgram/ml}, while postvaccination levels ranged from 0.161 to 1.192 micrograms/ml (GMT = 0.489 microgram/ml) . Five children who did not achieve postimmunization anti-PRP antibody levels greater than 1.0 microgram/ml received 15 micrograms of either PRP coupled to diphtheria toxoid (PRP-D) or PRP coupled to an outer membrane protein complex of Neisseria meningitidis group B (PRP-NOMP) conjugate vaccine . Anti-PRP antibody levels 1 month after immunization with HIB conjugate vaccines ranged from 1.51 to 10.35 micrograms/ml (GMT = 3.386 micrograms/ml) . Patients with extrahepatic biliary atresia and hepatoportoenterostomies who previously received the HIB-PRP vaccine should be revaccinated with PRP protein conjugate vaccines to ensure adequate protection against H . influenzae type b disease.

Biochim Biophys Acta, 1990 Aug 1, 1040(1), 84 - 8
Nonpolar interactions in the maleimide inactivation of Haemophilus influenzae D-lactate dehydrogenase; Denicola-Seoane A et al.; A series of N-alkylmaleimides varying in chain length from N-ethyl up to and including N-heptyl, was shown to effectively inactivate Haemophilus influenzae D-lactate dehydrogenase at pH 7.0 and 25 degrees C in processes proposed to involve covalent modification of cysteine residues . The inactivation proceeded through an initial reversible binding of maleimides facilitated by nonpolar interactions with a hydrophobic region of the enzyme . Subsequent irreversible inactivation of the enzyme indicated the modification of a fast-reacting group leading to approx . 80% loss of enzyme activity followed by a second slower-reacting modification process . At saturating concentrations of maleimides, the second inactivation process exhibited a common pseudo-first-order rate constant of 0.6 min-1 . The initial reversible binding of N-alkylmaleimides resulted in inhibition of the enzyme that was competitive with respect to NADH . Positive chain length effects were observed in the second-order rate constants for inactivation and in the 6-fold better binding of N-heptylmaleimide as compared to that for N-ethylmaleimide . It is suggested that the nonpolar interactions stabilizing the 1,4-dihydronicotinamide moiety of the reduced coenzyme also facilitate the initial binding of N-alkylmaleimides.

J Exp Med, 1990 Aug 1, 172(2), 497 - 507
Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation; Ramilo O et al.; Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in the meningeal inflammatory cascade, the results obtained by several groups of investigators have been discordant or, at times, contradictory . In the present study, homologous cytokines were applied to the rabbit meningitis model . Intracisternal administration of 10(2)-10(5) IU of purified rabbit TNF-alpha (RaTNF-alpha) produced significant cerebrospinal fluid (CSF) inflammation . A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant IL-1 beta (rrIL-1 beta) . Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response . In animals with Haemophilus influenzae type b lipooligosaccharide-induced meningitis, intracisternal administration of anti-rrIL-1 beta, anti-RaTNF-alpha, or both resulted in a significant modulation of meningeal inflammation . Simultaneous administration of 10(3) IU of RaTNF-alpha and 5 ng of rrIL-1 beta resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone . These data provide evidence for a seminal role of TNF-alpha and IL-1 beta in the initial events of meningeal inflammation.

Pediatrics, 1990 Aug, 86(2), 163 - 70
Subdural effusion and its relationship with neurologic sequelae of bacterial meningitis in infancy: a prospective study; Snedeker JD et al.; One hundred thirteen infants, aged 1 to 18 months, were screened systematically and serially using transillumination for the presence of subdural effusion during acute bacterial meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae, or Neisseria meningitidis . Effusion developed in 44 (39%) of the patients during the course of treatment . Young age, rapid onset of illness, low peripheral white blood cell count, and high cerebrospinal fluid levels of protein and bacterial antigen were associated with a higher likelihood of developing effusion . Although patients with effusion were more likely to have neurologic abnormalities both at the time of admission and at completion of therapy, and were more likely to have seizures during the course of treatment, there was no greater incidence of seizures, hearing loss, neurologic deficits, or developmental delay on longterm follow-up (median follow-up interval 5.5 years) in patients with effusion . Specific invasive therapy is not indicated in infants with meningitis and subdural effusion who are otherwise improving.

Jpn J Antibiot, 1990 Aug, 43(8), 1436 - 41
{A clinical evaluation of cefdinir in pediatric infections}; Katsushima N et al.; Cefdinir (CFDN), a new oral cephalosporin, was administered to 10 patients with various infections and the following results were obtained . 1 . Clinical responses in 10 patients (1 patient with rhinitis, 2 with sinusitis, 1 with pharyngitis, 1 with tonsillitis, 4 with scarlet fever and 1 with abscess) were excellent in 6 and good in 4 with an efficacy rate of 100% . 2 . Eleven species of bacteria were isolated (3 of Staphylococcus aureus, 6 of Streptococcus pyogenes and 2 of Haemophilus influenzae) and all of them were eradicated by the treatment with CFDN . 3 . No side effects or abnormal laboratory test values were noted . None of the patients refused to take the drug.

Nippon Hifuka Gakkai Zasshi, 1990 Aug, 100(9), 929 - 34
{The role of bacteria on facial rosacea-like dermatitis in adult type atopic dermatitis}; Noguchi T et al.; To investigate the role of bacteria on facial rosacea-like dermatitis lesion in adult type atopic dermatitis, we measured the numbers of bacteria on the skin, nasal and pharyngeal surface of each individual, and then examined its sensitivity to antibiotics . The numbers of bacteria on the surface of skin increased according to the severity of skin eruption . Staphylococcus aureus was detected from the skin and nasal surface more than pharyngeal surface . Bacteria on the pharyngeal surface were both staphylococcus aureus and haemophilus parainfluenzae . Therefore, it is suggested that bacterial flora on the pharynx is different from those of the skin and nose . The treatment with antibiotics was effective for exudative lesions, whereas lichenified lesion did not respond to antibiotic therapy . These results suggest that bacteria on the skin surface are one of precipitating factors of the rosacea-like dermatitis of atopic dermatitis.

Arch Fr Pediatr, 1990 Aug-Sep, 47(7), 491 - 5
{Therapeutic management of purulent meningitis in children . Report of 101 cases}; Slide precipitation: a simple method to type Actinobacillus (Haemophilus) pleuropneumoniae; Regional Veterinary Investigation Centre, Torhout, BelgiumSoluble thermostable antigens prepared from Actinobacillus pleuropneumoniae, as commonly applied in the ring precipitation test, were used in rapid slide tests . This method was easier to perform than the ring precipitation test and showed the same specificity . This specificity was higher than that obtained in slide agglutination tests using whole bacterial cells.

Pediatr Infect Dis J, 1990 Aug, 9(8), 555 - 61
Safety evaluation of PRP-D Haemophilus influenzae type b conjugate vaccine in children immunized at 18 months of age and older: follow-up study of 30,000 children; Vadheim CM et al.; We evaluated the safety of the PRP-D conjugate Hib vaccine (ProHIBit, Connaught) in 29,309 children vaccinated at 18-60 months of age in the Southern California Kaiser Permanente medical clinics during the period April 1, 1988, to July 31, 1989 . Surveillance for potential reactions involved postcard questionnaires, telephone surveys, reports of Kaiser staff and review of hospitalizations and covered two periods following immunization: (1) the first 48 hours and (2) days 2 through 30 . Surveillance for invasive Hib disease involved the above methods in addition to systematic reviews of laboratory and hospital records through January 31, 1990 . Rates of local and systemic reactions within 48 hours of vaccination with PRP-D alone were low (less than or equal to 2% for fever greater than 102 degrees F, local redness or swelling) and similar to those previously reported after vaccination with PRP . Hospitalization and seizures (0.15% and 0.09% of vaccinated children, respectively) occurring within 1 month of immunization appeared to be unrelated to vaccination . One 29-month-old child had onset of a fatal episode of Hib sepsis/meningitis within 48 hours of vaccination . Also, a 30-month-old child developed Hib meningitis 10 months after PRP-D vaccination . We conclude that PRP-D is safe when given alone or in combination with other childhood vaccines between 18 and 60 months of age.

Antimicrob Agents Chemother, 1990 Aug, 34(8), 1480 - 4
Problems with current recommendations for susceptibility testing of Haemophilus influenzae; Mendelman PM et al.; We compared results of MIC and disk susceptibility tests on Haemophilus test medium (HTM) and those on comparative media . Ampicillin MICs were determined with seven ampicillin-resistant, non-beta-lactamase-producing (AmprNBLP) isolates by using HTM and supplemented brain heart infusion (sBHI) agar . Ampicillin and amoxicillin-clavulanate disk tests with 16 AmprNBLP strains, 18 ampicillin-susceptible (Amps) isolates, and 17 ampicillin-resistant, beta-lactamase-producing (AmprBLP) strains were performed by using five media: laboratory-prepared HTM (PHTM), commercial HTM (CHTM), sBHI, enriched chocolate agar, and Mueller-Hinton chocolate agar . We observed that five of seven and three of seven AmprNBLP strains were misclassified as susceptible with PHTM (MIC, less than 2 micrograms/ml) with inocula of 10(3) and 10(5) CFU, respectively, but were resistant with sBHI (MIC, greater than or equal to 2 micrograms/ml) . Whereas Mueller-Hinton chocolate agar and enriched chocolate agar plates supported the growth of all 51 strains by the disk tests, 37% (19 of 51) and 8% (4 of 51) of strains did not grow on PHTM and CHTM, respectively . Lack of growth on PHTM was observed for all three phenotypes; 7 of 18 Amps, 4 of 17 AmprBLP, and 8 of 16 AmprNBLP strains did not grow . The four strains that did not grow on CHTM were all AmprNBLP isolates . Zone sizes were significantly larger on PHTM than on the other media . Of the strains that were evaluable by the new National Committee for Clinical Laboratory Standards guidelines with either PHTM or CHTM, all Amps strains were classified as susceptible . Among the AmprBLP strains, CHTM correctly identified all as resistant, whereas PHTM detected two isolates to be intermediate . Among the AmprNBLP strains, CHTM and PHTM misclassified four (33%) and five (62%) isolates, respectively, as susceptible; an additional isolate was identified as intermediate on both media . We conclude that there is strain-dependent growth on HTM, that adoption of this medium for routine Haemophilus susceptibility testing is problematic due to this growth variability, and that detection of AmprNBLP isolates would be unreliable.

Q J Med, 1990 Aug, 76(280), 799 - 816
Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis; Currie DC et al.; Thirty-eight patients with bronchiectasis and daily expectoration of purulent sputum despite conventional antibiotic courses were randomly allocated to receive a sachet of amoxycillin (3 g) or matched placebo twice daily for 32 weeks in a double-blind study . Nine patients (four amoxycillin, five placebo) were withdrawn from the study treatment; the response of the two patients (both on amoxycillin) withdrawn within the first six weeks was not assessed . The pretreatment characteristics of the two groups were similar . Independent assessment of overall response based on patients' diary cards showed that a higher proportion improved in the amoxycillin group (11 of 17) than in the placebo group (four of 19; p = 0.02) . Patients in the amoxycillin group spent significantly less time confined to bed and away from work during treatment . The frequency of exacerbations during the study treatment phase was similar in the two groups but they were less severe than before study treatment in the amoxycillin group . There was a greater reduction in purulent sputum volume between exacerbations during the study treatment in the amoxycillin group to 20 per cent of pretreatment volume than in the placebo group (88 per cent of pretreatment volume, p = 0.008), although the concentrations of Haemophilus spp . in sputum between exacerbations was similar in the two groups . Adverse effects experienced were minor except in one patient (amoxycillin) withdrawn after developing a rash and in six patients (three amoxycillin, three placebo) who had diarrhoea lasting more than one week necessitating withdrawal of two patients (one amoxycillin, one placebo) from study treatment . Sputum and stool cultures collected regularly during the study showed no important changes in the bacterial flora in either group . Prolonged higher-dose antibiotic therapy in these patients with severe purulent bronchiectasis significantly reduced the host (patient) inflammatory response to colonizing microorganisms and reduced morbidity.

Br J Clin Pract, 1990 Aug, 44(8), 329 - 31
Haemophilus aphrophilus endocarditis; Webb CH et al.; We report a case of Haemophilus aphrophilus endocarditis involving mitral and tricupsid valves in a boy with congenital heart disease . He had received dental treatment without antibiotic cover . Prolonged high-dose ampicillin with gentamicin was necessary for cure . Short courses of ampicillin alone may not successfully treat H . aphrophilus.

APMIS, 1990 Aug, 98(8), 753 - 7
In vitro activity of 9 antimicrobial agents against 177 strains of Haemophilus influenzae isolated from hospitalized patients; Teigen K et al.; In vitro activity of 4 commonly used and 5 new antibiotics was examined against 177 strains of Haemophilus influenzae . All strains were collected from various sites in patients with clinical infections . The study confirms that several newer antibiotics are useful alternatives to older drugs, as measured by in vitro activity . Ciprofloxacin and ofloxacin were the most active agents, (MIC90 0.012 micrograms/ml and 0.05 micrograms/ml respectively), followed by aztreonam (MIC90 0.1 micrograms/ml) and cefuroxime (MIC90 0.8 micrograms/ml) . A new macrolide, azithromycin (CP 62,993), was more active than erythromycin, MIC90 1.6 micrograms/ml vs 6.4 micrograms/ml . Beta-lactamase production was detected in 4.5% (8/177) of the strains . In vitro activity was the same against strains collected in 1985 and 1988 . No increase in beta-lactamase production was recorded.

J Clin Microbiol, 1990 Aug, 28(8), 1862 - 3
Comparison of the RIM-H rapid identification kit with conventional tests for the identification of Haemophilus spp; Palladino S et al.; A commercially available system, the RIM-H system (Austin Biological Laboratories, Austin, Tex.), was evaluated for its ability to rapidly and accurately identify various Haemophilus spp . A total of 110 clinical isolates were tested by both the RIM and conventional identification procedures . The RIM agreed with the standard identification for 100% of the Haemophilus influenzae (76 of 76) and 92.0% of the Haemophilus parainfluenzae (23 of 25) isolates tested . The identifications of Haemophilus parahaemolyticus, Haemophilus aphrophilus, and Haemophilus haemolyticus also correlated with those obtained by conventional methods . The RIM was found to be rapid and easy to use and was considered a suitable alternative to conventional identification procedures.

Antimicrob Agents Chemother, 1990 Aug, 34(8), 1473 - 9
In vitro evaluation of nicotinamide riboside analogs against Haemophilus influenzae; Godek CP et al.; Exogenous NAD, nicotinamide mononucleotide, or nicotinamide riboside is required for the growth of Haemophilus influenzae . These compounds have been defined as the V-factor growth requirement . We have previously shown that the internalization of nicotinamide riboside is energy dependent and carrier mediated with saturation kinetics . Thionicotinamide riboside, 3-pyridinealdehyde riboside, 3-acetylpyridine riboside, and 3-aminopyridine riboside were prepared from their corresponding NAD analogs . These compounds and several other nicotinamide riboside analogs were evaluated for their ability to support the growth of H . influenzae and for their ability to block the uptake of {carbonyl-14C}nicotinamide riboside by H . influenzae . 3-Aminopyridine riboside blocked the uptake of {carbonyl-14C}nicotinamide riboside and inhibited the growth of H . influenzae when NAD, nicotinamide mononucleotide, or nicotinamide riboside served as the V factor . The antibacterial activity of 3-aminopyridine riboside was found to be specific for H . influenzae but had no effect on the growth of Staphylococcus aureus or Escherichia coli . In additional experiments by reversed-phase high-performance liquid chromatography, it was determined that whole cells of H . influenzae degrade 3-aminopyridine adenine dinucleotide to 3-aminopyridine riboside, which is then internalized . Inside the cell, 3-aminopyridine riboside has the ability to interfere with the growth of H . influenzae by an undetermined mechanism.

J Antimicrob Chemother, 1990 Aug, 26(2), 237 - 46
Temafloxacin in acute purulent exacerbations of chronic bronchitis; Davies BI et al.; Temafloxacin hydrochloride, a new fluoroquinolone, was given orally in doses of 300 or 600 mg twice daily for ten days to 36 patients, all hospitalized because of severe acute purulent exacerbations of chronic bronchitis . Sputum cultures before, during and after treatment showed that the infection was eliminated in 12/18 evaluable patients given 300 mg and in 13/16 receiving the 600 mg doses . Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae were effectively eliminated, but only half the Pseudomonas aeruginosa infections were eradicated . MICs for most pathogens were 1 mg/l or less (including the majority of the pneumococci) but the MICs for Ps . aeruginosa ranged from 0.5 to greater than 16 mg/l, those for 10 of the 22 strains being greater than 2 mg/l . Pharmacokinetic studies on serum and sputum specimens showed serum Cmax values of 3.5 and 6.0 mg/l, the sputum Cmax being 2.35 and 4.17 mg/l after the different doses . No interaction with concomitant theophylline could be found . Two patients complained of moderate nausea or water-brash . Temafloxacin can be considered safe and effective at these dosages, but for Ps . aeruginosa infections higher dosages need to be investigated.

J Antimicrob Chemother, 1990 Aug, 26(2), 209 - 13
Ceftibuten--in-vitro activity against respiratory pathogens, beta-lactamase stability and mechanism of action; Wise R et al.; The in-vitro activity of ceftibuten against respiratory pathogenic bacteria was studied and compared with that of other oral beta-lactam agents . Ceftibuten displayed high activity against Haemophilus influenzae and Branhamella catarrhalis . There was reduced activity against Streptococcus pneumoniae (MIC90 16 mg/l) . The protein binding of ceftibuten was 77% and the primary target site PBP 3 . A high degree of stability to beta-lactamase hydrolysis was observed.

Ir J Med Sci, 1990 Aug, 159(8), 231 - 2
Increased ampicillin resistance in Haemophilus influenzae in Northern Ireland hospitals; Murphy PG et al.; Twenty-nine of one hundred and ninety-three (15%) clinical isolates of Haemophilus influenzae from Northern Ireland hospitals during 1985-1986 were found to be ampicillin resistant . This is twice the national average for the same period and 65% increase since a similar report in Northern Ireland three years previously . Computerised monitoring of routine specimens has shown this resistance level to be maintained in 1989 . Susceptibility to other antimicrobials is discussed.

Microb Pathog, 1990 Aug, 9(2), 81 - 93
Induction of an immune response to the porin of Haemophilus influenzae type b by monoclonal anti-idiotypic antibodies; Hamel J et al.; Monoclonal anti-idiotypes were generated against monoclonal antibody (mAb) Hb-2 which recognized a highly conserved epitope on the outer membrane porin protein from Haemophilus influenzae type b (Hib) . Four hybridomas reacting with F(ab') 2 fragments of Hb-2 were selected and characterized . Inhibition studies using syngeneic anti-anti-idiotypic antisera suggested that at least three different antigenic determinants on Hb-2 were recognized by these monoclonal anti-idiotypes . The binding of each anti-idiotype to Hb-2 was inhibited by Hb-2 whereas the reaction was not affected by any other anti-Hib mAb . Complete inhibition of the binding of anti-idiotype to the idiotype could be achieved with 10 micrograms of total outer membrane protein (OMP) from Hib suggesting that the anti-idiotypes might be directed against paratope-associated idiotypes . Outer membrane antigens not recognized by mAb Hb-2 did not inhibit the reaction . Furthermore, the pre-incubation of Hb-2 with each anti-idiotype specifically prevented the reaction of Hb-2 with its antigen . Antibodies with specificity for the porin were generated in guinea pigs immunized with anti-idiotypes AHb-22 and AHb-23 . This study indicates that these particular monoclonal anti-idiotypes may be used as an antigen substitute for the porin of Hib in a xenogeneic species.

J Clin Microbiol, 1990 Aug, 28(8), 1720 - 4
Antigenic relationships among the porin proteins of encapsulated Haemophilus influenzae clones; Martin D et al.; Monoclonal antibodies (Mabs) specific for Haemophilus influenzae were generated to identify antigenic determinants shared among encapsulated H . influenzae clones . Sixteen MAbs reacted by Western immunoblot with a protein of an approximate molecular size of 40 kilodaltons corresponding to the P2 major outer membrane protein (porin) . These MAbs also reacted with purified and recombinant H . influenzae porin . Fourteen of the MAbs recognized cell surface-exposed epitopes, and two of the MAbs, P2-16 and P2-17, identified epitopes that are not present or are not accessible on the cell surface . The reactivity spectrum of the MAb panel was studied by dot immunoassay against 32 serologically nontypeable and 119 encapsulated H . influenzae strains recovered worldwide, representing the major serotype a, b, and d clone families . MAbs P2-4 and P2-6 recognized only serotype b clones assigned to primary phylogenetic division I . These clones account for more than 99% of all invasive episodes worldwide . MAbs P2-3, P2-8, and P2-11 reacted with division I serotype b isolates and also identified all genetically allied strains expressing serotype a and d polysaccharide capsules . In contrast, none of the 16 MAbs reacted with genetically divergent serotype a or b clones assigned to primary phylogenetic division II . These results demonstrate that, in general, the patterns of P2 protein surface epitope exposure are cognate with genetic lineages of encapsulated H . influenzae strains and support the hypothesis that the population structure of encapsulated H . influenzae is predominantly clonal.

Lancet, 1990 Jul 21, 336(8708), 159 - 60
Cross-infection by non-encapsulated Haemophilus influenzae; Gough J et al.; From October, 1988, to January, 1989, 18 patients admitted to an acute medical chest ward were infected with an ampicillin-resistant beta-lactamase-producing strain of Haemophilus influenzae . All 18 isolates were non-encapsulated strains of biotype III and showed identical cell envelope protein profiles, as judged by sodium dodecyl sulphate-polyacrylamide gel electrophoresis . The organism was not isolated from repeated environmental samples but there was strong circumstantial evidence that a spirometer was a common iatrogenic source of the cross-infection.

Infect Immun, 1990 Jul, 58(7), 2343 - 51
Effect of mutations in lipooligosaccharide biosynthesis genes on virulence of Haemophilus influenzae type b; Cope LD et al.; Chemical mutagenesis techniques and genetic transformation methods were used to construct isogenic mutants of Haemophilus influenzae type b (Hib) defective in the ability to synthesize lipooligosaccharide (LOS) . A mutant (17B) which expressed a LOS molecule with an altered oligosaccharide was less virulent than the wild-type parent strain, as determined by measurement of the ability of these strains to produce bacteremia in infant rats after intranasal challenge . Further mutagenesis of this mutant strain yielded two new mutants with different LOS phenotypes . Mutant 7A was slightly sensitive to the bactericidal activity present in normal infant rat serum and was even less virulent than its immediate parent strain (17B) in the intranasal challenge model . However, both mutants 17B and 7A could produce bacteremia and meningitis when introduced into infant rats by the intraperitoneal route . The other LOS mutant (14A) derived from mutant 17B exhibited a level of virulence equivalent to that of the original wild-type strain . Genetic transformation of wild-type chromosomal DNA into the essentially avirulent mutant 7A and selection of transformants on the basis of their LOS antigenic characteristics resulted in the sequential restoration of full virulence to this mutant . These findings suggest that LOS is involved on at least two different levels in the ability of Hib to produce invasive disease in the infant rat model . Changes in LOS phenotype can independently affect the ability of Hib to produce bacteremia after intranasal challenge and the sensitivity of Hib to killing by normal infant rat serum . These results reinforce the significance of Hib LOS in the expression of virulence by this pathogen.

Nucleic Acids Res, 1990 Jul 11, 18(13), 3903 - 11
Cloning, nucleotide sequence, and expression of the HincII restriction-modification system; Ito H et al.; Two genes, coding for the HincII from Haemophilus influenzae Rc restriction-modification system, were cloned and expressed in Escherichia coli RR1 . Their DNA sequences were determined . The HincII methylase (M.HincII) gene was 1,506 base pairs (bp) long, corresponding to a protein of 502 amino acid residues (Mr = 55,330) . The HincII endonuclease (R.HincII) gene was 774 bp long, corresponding to a protein of 258 amino acid residues (Mr = 28,490) . The amino acid residues predicted from the R.HincII and the N-terminal amino acid sequence of the enzyme found by analysis were identical . These methylase and endonuclease genes overlapped by 1 bp on the H . influenzae Rc chromosomal DNA . The clone, named E . coli RR1-Hinc, overproduced R.HincII . The R.HincII activity of this clone was 1,000-fold that from H . influenzae Rc . The amino acid sequence of M.HincII was compared with the sequences of four other adenine-specific type II methylases . Important homology was found between tne M.HincII and these other methylases.

Antimicrob Agents Chemother, 1990 Jul, 34(7), 1456 - 8
Comparative in vitro activity of cefixime against Haemophilus influenzae isolates, including ampicillin-resistant, non-beta-lactamase-producing isolates, from pediatric patients; Mortensen JE et al.; The in vitro activity of cefixime was comparatively tested against 232 non-type b and 102 type b isolates of Haemophilus influenzae derived from clinical specimens of pediatric patients, including 10 non-type b strains that did not produce beta-lactamase and demonstrated resistance to ampicillin . Cefixime was active against the ampicillin-susceptible and ampicillin-resistant, beta-lactamase-producing isolates; however, its activity against some non-beta-lactamase-producing, ampicillin-resistant isolates appeared to be limited.

Antimicrob Agents Chemother, 1990 Jul, 34(7), 1366 - 70
In vitro activity of E-1040, a 3-substituted cephalosporin, against pathogens from cystic fibrosis sputum; Stutman HR et al.; On the basis of preliminary in vitro data, we evaluated E-1040, a new cephalosporin, against 188 cystic fibrosis (CF) sputum isolates obtained from 26 CF centers in the United States . These isolates included mucoid and nonmucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli . In addition to MICs measured under standard conditions, selected isolates were tested at various pH values, inoculum sizes, and diluent (CF serum and sputum) conditions . E-1040 activities (MICs for 50 and 90% of the strains) against the isolates were as follows: P . aeruginosa (mucoid and nonmucoid), 1 and 4 micrograms/ml; P . cepacia, 4 and 16 micrograms/ml; S . aureus, 8 and 8 micrograms/ml; H . influenzae, 1 and 4 micrograms/ml; and E . coli, less than or equal to 0.12 and less than or equal to 0.12 microgram/ml . E-1040 activity against mucoid P . aeruginosa was 4-fold greater than that of aztreonam, 16-fold greater than that of ceftazidime, and 32-fold greater than that of piperacillin . E-1040 was similar to other broad-spectrum cephalosporins against S . aureus, H . influenzae, and E . coli . Bactericidal activity was less than or equal to 1 dilution of MIC for 88% of the strains, although kinetic studies with mucoid strains of P . aeruginosa demonstrated effective killing only at eight times the MIC . Variations in pH from 5 to 8, in inoculum size from 10(3) to 10(7) CFU/ml, and in diluent (CF serum or CF sputum) did not affect E-1040 activity.

Anaesthesia, 1990 Jul, 45(7), 561 - 2
Respiratory tract infection and anaesthesia . Haemophilus influenzae pneumonia that developed under anaesthesia; Campbell NN; A 2-year-old boy with symptoms of a minor upper respiratory tract infection developed Haemophilus influenzae pneumonia that presented as hypoxaemia under anaesthesia for minor emergency surgery . The patient required 72 hours of mechanical ventilation in an intensive care unit after the anaesthetic and thereafter made an uneventful recovery . The value of pre-operative chest radiology and the possible contributory effect of anaesthesia are discussed.

Rev Infect Dis, 1990 Jul-Aug, 12(4), 708 - 15
Life-threatening Haemophilus influenzae infections in Scandinavia: a five-country analysis of the incidence and the main clinical and bacteriologic characteristics; Peltola H et al.; The five countries of Scandinavia (Denmark, Finland, Iceland, Norway, and Sweden) comprise 22.6 million inhabitants and rather homogeneous socioeconomic conditions . A survey of systemic Haemophilus influenzae diseases over the last decades revealed that the reported incidence of H . influenzae disease is increasing . In recent years, the overall incidence has been 3.5 cases per 100,000 people each year (800 cases annually); in children less than 5 years of age, the annual incidence has been 49 cases per 100,000 . Meningitis represents only 52% of all systemic H . influenzae diseases, but lack of reliable data may obscure the importance of other entities . Few strains (less than 5%) are beta-lactamase-positive, and the case fatality rate is 3% . Analysis of seasonal variation shows peaks in June and September-October . If the efficacy of the H . influenzae conjugate vaccines were as high as that of a conjugate vaccine used in Finland during 1986-1987 (approximately 85% efficacy), then at least an 80% reduction in life-threatening H . influenzae infections would be achieved annually by routine immunization before or at the age of 6 months.

Res Vet Sci, 1990 Jul, 49(1), 8 - 13
Use of monoclonal antibodies for classifying Actinobacillus (Haemophilus) pleuropneumoniae; Lida J et al.; The serological typing (by enzyme-linked immunosorbent assay) of 119 isolates of Actinobacillus (Haemophilus) pleuropneumoniae (representing in varying numbers the 12 serovars of this taxon) by monoclonal antibodies derived from the reference strains of serovars 1 to 5 in general correlated reasonably with the serotype previously established for these strains by conventional procedures employing polyclonal antisera . However, where there were reasonable numbers of isolates representing a given serovar to provide a decision, there was no instance where the correlation between the monoclonal and the polyclonal antibody was in complete accord . In addition, some of the differences between monoclonal and polyclonal antibody binding with some isolates suggest that the distribution of the serotype-specific antigens within the taxon may be even more complex than has previously been supposed.

Pediatr Infect Dis J, 1990 Jul, 9(7), 488 - 94
A population-based retrospective assessment of the disease burden resulting from invasive Haemophilus influenzae in infants and young children in Santiago, Chile; Ferreccio C et al.; Clinical discharge and laboratory records were reviewed in the seven government hospitals that provide care for 93% of the pediatric population of Santiago, Chile, to detect cases of meningitis and other invasive (bacteremia-associated) infections caused by Haemophilus influenzae . infections that occurred in children less than five years of age from January, 1985, through December, 1987, were recorded and matched with census data to calculate incidence rates . The incidence of meningitis and non-meningitis syndromes peaked in the 6- to 11-month age group and tapered sharply after 12 months of age . The city-wide incidence (ca . 21.6 cases/10(5) children less than 5 years of age) is one-third to one-half that reported for the general pediatric population in the United States . However, there is much evidence for under-reporting in Santiago . In Area Norte, served by Roberto del Rio Children's Hospital where H . influenzae has been a subject of research by pediatricians for years, the incidence of invasive H . influenzae infections (42.5/105) is approximately two-fold higher than the rest of Santiago . The cumulative proportions of episodes of H . influenzae disease occurring in successively older age groups closely parallel the pattern seen in the general United States pediatric population . Although only ca . 20% of all episodes occur during the first 6 months of life, nearly 80% of episodes are seen by 18 months of age . Based on the observed incidence rates, the apparent underreporting and the high city-wide case fatality of Hib meningitis (16%), invasive H . influenzae infections represent an important public health problem in Santiago, Chile.

J Infect Dis, 1990 Jul, 162(1), 248 - 50
C4B deficiency: a risk factor for bacteremia with encapsulated organisms; Bishof NA et al.; The fourth component of complement (C4) is crucial to the activation of the classical complement pathway, a key defense against invading microorganisms . The two isotypes of C4, C4A and C4B, have very different in vitro activities . An increased incidence of total C4B deficiency was found in white patients with Streptococcus pneumoniae, Haemophilus influenzae, or Neisseria meningitidis infection (14% of bacteremic children vs . 2% of race-matched controls, P = .02) . In black patients, however, there was no difference in incidence of C4B deficiency between bacteremic patients and race-matched controls (7% and 5%, respectively, P greater than .5) . These data suggest that, at least in whites, total C4B deficiency is a risk factor for invasive disease with these three encapsulated organisms.

J Infect Dis, 1990 Jul, 162(1), 163 - 71
Bactericidal and opsonic activity of IgG1 and IgG2 anticapsular antibodies to Haemophilus influenzae type b; Amir J et al.; Complement-mediated bactericidal and opsonic activity of IgG1 and IgG2 antibodies to Haemophilus influenzae type b polysaccharide (polyribosyl ribitol phosphate {PRP}) were investigated . The antibody sources were IgG1 or IgG2 subclass polyclonal antibody fractions prepared by immunoabsorption of sera from adults immunized with PRP or PRP-diphtheria toxoid conjugate vaccine or clonally purified anti-PRP antibodies from eight adults immunized with PRP vaccine . In bactericidal assays using an inoculum of 3 x 10(3) colony-forming units (cfu)/ml, twofold lower concentrations of IgG1 compared with IgG2 antibody were required for 50% killing . With approximately 10(6) cfu/ml, IgG1 antibody killed 3 logs more of bacteria than were killed by comparable concentrations of IgG2 antibody . The IgG1 antibody also required lower concentrations of complement than did the IgG2 antibody for comparable bacteriolytic activity . Clonally purified IgG1 and IgG2 anti-PRP antibodies from most individuals showed similar relative differences in bactericidal activity . IgG1 anti-PRP antibody was also more efficient than IgG2 anti-PRP antibody in enhancing the uptake of radiolabeled type b H . influenzae by human polymorphonuclear leukocytes in the presence of complement and in protecting infant rats from developing bacteremia . However, the differences in opsonic or protective activity of the two subclasses were smaller than the differences in bactericidal activity . Thus, IgG1 anti-PRP antibody is functionally more effective than IgG2 antibody, but it is likely that both subclasses can confer protection against disease.

J Infect Dis, 1990 Jul, 162(1), 139 - 47
Cerebrospinal fluid cachectin/tumor necrosis factor-alpha and platelet-activating factor concentrations and severity of bacterial meningitis in children; Arditi M et al.; In prospective studies, tumor necrosis factor (TNF alpha) was detected in cerebrospinal fluid (CSF) of 33 of 38 children with bacterial meningitis (BM) but in none of 15 with viral meningitis/encephalitis (P less than .001) . BM CSF TNF alpha (less than 35 to greater than 25,500 pg/ml) correlated with CSF bacterial density (P less than .01), CSF protein (P less than .001), endotoxin (LPS) in gram-negative disease (P less than .01), and consecutive febrile hospital days (P less than .001); initial CSF TNF alpha greater than 1000 pg/ml was associated with seizures (P less than .05) . Only 5 children with BM (13%) had detectable plasma TNF alpha activity on admission . A higher proportion who died had detectable plasma TNF alpha activity compared with survivors (3/4 vs . 2/34, P less than .005) . Platelet-activating factor (PAF) in CSF was higher in 19 children with Haemophilus influenzae meningitis than in 17 controls (P less than .01) and correlated with bacterial density (P less than .01), CSF LPS (P less than .01), CSF TNF alpha levels (P less than .01), and the Herson-Todd severity score (P less than .01) . Elevated CSF TNF alpha and PAF are often present in children with BM and are associated with seizures and severity of disease . Detectable CSF TNF alpha appears to distinguish BM from viral meningitis.

Eur Respir J, 1990 Jul, 3(7), 840 - 1
Haemophilus influenzae lobar pneumonia in the father of a child with epiglottitis; Manji H et al.; We present a case of Haemophilus influenzae lobar pneumonia in the father of a child admitted with acute epiglottitis caused by the same organism . The suggestion that adult, as well as child, contacts for Haemophilus influenzae epiglottitis should be prophylactically treated is discussed.

Pathology, 1990 Jul, 22(3), 162 - 4
Evaluation of a selective medium for the isolation and differentiation of Haemophilus influenzae and Haemophilus parainfluenzae from the respiratory tract of chronic bronchitics; Taylor DC et al.; Respiratory tract specimens from chronic bronchitic patients were cultured for Haemophilus species on conventional chocolate agar and a modified sucrose medium in order to determine the accuracy of the new medium in differentiating Haemophilus influenzae from Haemophilus parainfluenzae strains . Haemophilus influenzae biotypes II and III and Haemophilus parainfluenzae biotypes I and II were found to be the predominant strains isolated from the respiratory tract . The modified sucrose medium was found to be a rapid and reliable means of differentiating Haemophilus influenzae from Haemophilus parainfluenzae by sucrose fermentation, on initial isolation.

Avian Dis, 1990 Jul-Sep, 34(3), 643 - 5
Serotyping of Haemophilus paragallinarum by the Page scheme: comparison of the use of agglutination and hemagglutination-inhibition tests; Blackall PJ et al.; Seventy-two isolates of Haemophilus paragallinarum were serotyped according to the Page scheme, using a new hemagglutination-inhibition (HI) test . The results were compared with the plate agglutination method conventionally used in the Page scheme . The HI test used washed cells of H . paragallinarum, glutaraldehyde-fixed chicken erythrocytes, and rabbit antisera originally produced for the agglutination method . For 49 of the isolates, there was complete correlation between the results of the HI serotyping test and the previously performed agglutination test--23 were serovar A, two were serovar B, and 24 were serovar C . The other 23 isolates were nontypable by the agglutination test, but 21 of them could be serotyped by the HI method--six as serovar A, two as serovar B, and 13 as serovar C . Nine isolates required treatment of the bacterial cells with hyaluronidase for the expression of hemagglutination (HA) activity . Two isolates did not have HA activity despite hyaluronidase treatment and so could not be serotyped by the HI test.

Respir Med, 1990 Jul, 84(4), 325 - 30
Antibacterial and mutagenic activity of inhaled bronchodilators on the respiratory pathogen Haemophilus influenzae; Powell M et al.; The U.K . prevalence of non-beta-lactamase-mediated resistance to ampicillin among Haemophilus influenzae reached 4% in 1986 . The majority (70%) of isolates of this type come from sputa of patients with chronic obstructive airways disease . This study investigated whether bronchodilator drugs delivered directly to the respiratory tract have any antibacterial activity and/or play a role in promoting selection of organisms with this type of resistance . Antibacterial activity was detected in two out of six pharmaceutical preparations for nebulization examination but was entirely attributable to the preservative (benzalkonium chloride) in them . Exposure of ampicillin-susceptible H . influenzae (minimum inhibitory concentration 0.25 mg l-1) to concentrations of salbutamol, fenoterol and beclomethasone theoretically attainable in vivo resulted, after 48 h, in isolation of colonies with reduced susceptibility to ampicillin (minimum inhibitory concentration 1-4 mg l-1) but reversion to beta-lactam susceptibility occurred following serial subculture on chocolate agar . Organisms with stable reduced susceptibility to ampicillin were obtained when exposure to one of these three bronchodilators in broth was followed by serial subculture on agar containing the same preparations at equivalent concentrations and when the period of exposure to salbutamol at 100 mg l-1 in broth was extended to 5 days . The occurrence of these phenomena in vivo might be contributing to failures in treatment of exacerbations with ampicillin and to an increasing prevalence of beta-lactamase-negative, ampicillin-resistant H . influenzae.

Jpn J Antibiot, 1990 Jul, 43(7), 1214 - 24
{Synergy between sulbactam and ampicillin or cefoperazone in antimicrobial activity against beta-lactamase producing microorganisms . Results with the use of microdilution broth method}; Deguchi K et al.; Antimicrobial activities of sulbactam (SBT) with ampicillin (ABPC) or with cefoperazone (CPZ), in other words, the effects of SBT, an beta-lactamase inhibitor, against beta-lactamase producing strains of clinical isolates, were studied using microdilution broth method . 1 . beta-Lactamase producing strains such as Staphylococcus aureus, Branhamella catarrhalis, Haemophilus influenzae, Escherichia coli and Klebsiella pneumoniae decompose benzylpenicillin (PCG) which is one of substrates of the acid-metry disc method and show a strong reaction, while they do not decompose cefazolin (CEZ), another substrate, showing no or weak reaction . Thus, it is suspected that beta-lactamases produced by these organisms are mainly penicillinase (PCase) . MIC-distributions of ABPC and CPZ against these clinical isolates which seemed to produce PCase shifted to lower MIC ranges with MIC's reduced to 1/4 or below when 0.025 to 0.39 microgram/ml of SBT was added . 2 . It appears that beta-lactamase produced by Proteus vulgaris may be oxyiminocephalosporinase (CXase), because P . vulgaris showed strong reaction on CEZ, but moderate reaction on PCG in the acid-metry disc method . MIC-distribution of ABPC and CPZ against P . vulgaris shifted to a lower range with MIC's of 1/4 or below when 0.20 to 0.39 microgram/ml of SBT was added . 3 . All the test strains of Pseudomonas aeruginosa showed strong reaction on CEZ but only 56% of the test strains showed reaction on PCG . It appears that the beta-lactamases which showed strong reaction on CEZ is cephalosporinase and is encoded in chromosome, while those beta-lactamase that showed strong reaction on PCG is encoded in a plasmid which was acquired secondarily by P . aeruginosa . MIC-distribution of CPZ against P . aeruginosa shifted to a lower range with MIC values of 1/2 or below with the addition of SBT at 1.56 micrograms/ml . 4 . It appears that the synergy of SBT with ABPC or with CPZ against the PCase or CXase producing strains may occur in the presence of SBT at a concentration far less than that reported previously.

J Gen Microbiol, 1990 Jul, 136 ( Pt 7), 1203 - 9
Urogenital, maternal and neonatal isolates of Haemophilus influenzae: identification of unusually virulent serologically non-typable clone families and evidence for a new Haemophilus species; Quentin R et al.; A collection of 117 strains of Haemophilus influenzae, including 112 non-typable isolates recovered predominantly in the USA and France from genital, obstetric and neonatal sources, was characterized by the electrophoretic mobilities of 10 metabolic enzymes . Eighty-six distinctive multilocus chromosomal genotypes (electrophoretic types, ETs) were distinguished on the basis of allele profiles at the enzyme loci . Isolates of five allied biotype IV ETs were highly divergent from all other strains and hybridization of chromosomal DNA revealed that they undoubtedly represent a previously unrecognized species of Haemophilus . Isolates representing these ETs were recovered predominantly from obstetric infections and serious neonatal diseases and apparently possess specific tropism for the genital tract . Strains of these five ETs were present in samples from both the USA and France, but only in the USA did they cause bacteraemia and meningitis, an occurrence which probably reflects differences in patient management between the two countries . Although strains assigned to H . influenzae (sensu stricto) were strongly polymorphic in multilocus enzyme genotype, 69% of isolates recovered from patients with meningitis and/or septicaemia were assigned to only two clone families, a result suggesting that some serologically nontypable strains of H . influenzae originating from the genital tract are unusually virulent.

J Antimicrob Chemother, 1990 Jul, 26(1), 71 - 9
Antibacterial activity of cefpodoxime proxetil in a pharmacokinetic in-vitro model; Wiedemann B et al.; The antibacterial activity of cefpodoxime proxetil was studied in an in-vitro model simulating doses of 100, 200 and 400 mg . Strains of Klebsiella spp . Proteus mirabilis, Escherichia coli, Streptococcus pyogenes, and Haemophilus influenzae were effectively reduced by a dose of 200 mg . While for Esch . coli no dose-activity relationship was observed--the maximal effect was achieved with a simulated dose of 100 mg--Staphylococcus aureus could be reduced effectively only by a simulated dose of 400 mg . The lower doses showed stepwise lower activities . Apart from broad spectrum beta-lactamases like SHV 2 or TEM 5 the presence of plasmid coded beta-lactamases in Esch . coli and H . influenzae did not affect the antibacterial activity of cefpodoxime proxetil . The results show that cefpodoxime was more active against Gram-negative bacteria than amoxycillin, and comparable activity to intramuscular cefotiam in the in-vitro model.

Pediatr Neurol, 1990 Jul-Aug, 6(4), 260 - 4
Haemophilus influenzae meningitis with prolonged hospital course; Martin LD et al.; A retrospective evaluation of Haemophilus influenzae type b meningitis observed over a 2-year period documented 86 cases . Eight of these patients demonstrated an unusual clinical course characterized by persistent fever (duration: greater than 10 days), cerebrospinal fluid pleocytosis, profound meningeal enhancement on computed tomography, significant morbidity, and a prolonged hospital course . The mean age of these 8 patients was 6 months, in contrast to a mean age of 14 months for the entire group . Two patients had clinical evidence of relapse . Four of the 8 patients tested for latex particle agglutination in the cerebrospinal fluid remained positive after 10 days . All patients received antimicrobial therapy until they were afebrile for a minimum of 5 days . Subsequent neurologic examination revealed a persistent seizure disorder in 5 patients (62.5%), moderate-to-profound hearing loss in 2 (25%), mild ataxia in 1 (12.5%), and developmental delay with hydrocephalus which required shunting in 1 (12.5%) . One patient had no sequelae.

Antimicrob Agents Chemother, 1990 Jul, 34(7), 1354 - 9
Sequence analysis and evolutionary perspectives of ROB-1 beta-lactamase; Juteau JM et al.; The nucleotide sequence of the ROB-1 beta-lactamase gene from Haemophilus influenzae plasmid RRob was determined . The structural gene encodes a polypeptide of 305 amino acids, with an estimated molecular mass of 30,424 for the mature form of the protein . The ROB-1 gene showed low homologies with other beta-lactamases at the nucleic acid level . By using two statistical computer methods, assessment of the extent of similarity between ROB-1 and other known beta-lactamase amino acid sequences suggested that ROB-1 is a class A enzyme . Alignment of class A beta-lactamases with ROB-1 identified conserved residues . The use of a mutation matrix for detecting distance relationships indicated that ROB-1 has higher values and homologies with beta-lactamases of gram-positive bacteria, giving insight into its ancestry and divergence.

Rev Infect Dis, 1990 Jul-Aug, 12(4), 628 - 35
Bacteremic disease due to Haemophilus influenzae capsular type f in adults: report of five cases and review; Slater LN et al.; Five cases of bacteremic infections due to Haemophilus influenzae type f in adults are described, and previous reports of type f disease in nonpediatric patients are reviewed . Respiratory tract infections were most common in our series (two cases of pneumonia, one of epiglottitis, and one of nosocomial septicemia probably resulting from aspiration pneumonitis) . All of these patients had factors predisposing them to respiratory tract infections, e.g., neurologic disease, congestive heart failure, or cigarette smoking . A fifth patient, who was bacteremic without an apparent primary focus, had dysgammaglobulinemia . Six episodes of bacteremia occurred in five patients; 11 of 13 cultures of blood obtained before parenteral antibiotic therapy were positive . All isolates were biotype I and susceptible to ampicillin . Antibiotic therapy was curative in cases of proved respiratory tract infection but failed in the setting of nosocomial septicemia, perhaps because of delayed initiation . The brevity of antibiotic treatment of the cryptogenic bacteremia permitted infection of a prosthetic vascular graft and recurrent bacteremia . Graft removal and repeated antibiotic therapy were curative.

J Clin Pathol, 1990 Jul, 43(7), 581 - 3
Evaluation of two rapid methods for identifying and biotyping Haemophilus influenzae; Murphy PG et al.; Several rapid method kits (one to four hours) have become available for the identification of Haemophilus and related genera . Two kits (the "Rapid NH" system and the "RIM Haemophilus" system), which include the identification and biotyping of H influenzae, were investigated for the rapid identification and biotyping of 193 isolates of H influenzae and the results compared with those obtained by more standard overnight methods . The kits were convenient to use and gave reliable and rapid speciation of all isolates . Both test systems were unreliable for biotyping: 42 isolates were wrongly biotyped by the RIM kit and 40 isolates wrongly biotyped by the rapid NH kit . It is concluded that the test kits may be useful for the rapid identification of H influenzae but that they are not reliable for the biotyping of this species.

Am J Med Sci, 1990 Jul, 300(1), 45 - 52
Pneumococcal vaccination: work to date and future prospects; Musher DM et al.; In our opinion, the conclusion from all these studies is that pneumococcal polysaccharides in the form in which they have been administered are relatively poor immunogens when compared, for example, to certain proteins such as tetanus toxoid . Had pneumococcal vaccination been the success that might reasonably have been predicted, there would be no argument, this many years later, over its merits . Although polysaccharide vaccines appear to have been effective in mass vaccination programs and in epidemic situations where presumably healthy adults have been involved, it has been more difficult to document their efficacy in individuals who are most in need of them, namely those with aberrant or senescent immune systems . There seems to be no disagreement that antibody at some concentration (the precise level remains to be determined) will, in general, be associated with protection, although in any one individual, for a variety of reasons, infection with a vaccine serotype might still occur . Thus, the clear direction for the future should be not to argue further the merits of currently available vaccine preparations, but rather to work rapidly and efficiently to develop and test new and more effective polysaccharide antigens . Studies in the past 10 years have shown that the polyribosyl ribitolphosphate (PRP) of Haemophilus influenzae type b is a far more effective antigen when conjugated to diphtheria toxoid . For example, in a study in our laboratory, vaccination of healthy young adults with PRP-conjugated diphtheria toxoid yielded serum antibody levels 10- to 100-fold higher than after PRP alone . Responses may be even better if other proteins are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioorg Khim, 1990 Jul, 16(7), 889 - 97
{Isolation and characteristics of new restriction endonucleases from Haemophilus influenzae}; Lazariavichiute LG et al.; Various strains of Haemophilus influenzae have been examined for the presence of site-specific endonuclease activities, and eleven restriction endonucleases have been isolated from seven strains . For all the endonucleases recognition sequences were determined, for three of them cleavage sites being identified . The enzymes proved to be isoschizomers of known endonucleases, viz . Hin1 I, Hin8 I--Acy I; Hin1 II, Hin8 II--Nla III; Hin2 I, Hin5 I--Hpa II; Hin3 I--Cau II; Hin5 II--Asu I; Hin5 III--Hind III; Hin6 I, Hin7 I--Hha I . Restriction endonucleases Hin1 I, Hin1 II and Hin6 I recognize nucleotide {formula: see text} sequences 5'GRCGPYC, 5'CATG, 5'GCGC, respectively, and cleave them as indicated by arrows.

Antimicrob Agents Chemother, 1990 Jul, 34(7), 1407 - 13
Enhancement of the in vitro and in vivo activities of clarithromycin against Haemophilus influenzae by 14-hydroxy-clarithromycin, its major metabolite in humans; Hardy DJ et al.; MICs of clarithromycin and its major human metabolite, 14-hydroxy-clarithromycin, for Haemophilus influenzae in combination were reduced two- to fourfold compared with the MICs of each compound alone . Serum reduced the MICs of the parent compound and metabolite two- to fourfold compared with the MICs in medium without serum . In serum spiked with clinically relevant concentrations of clarithromycin and 14-hydroxy-clarithromycin at a fixed ratio of 4:1, 15 of 16 strains (94%) were inhibited and killed by combinations containing 1.2 and 0.3 micrograms/ml, respectively . In time kill experiments, the combination of parent compound and metabolite at one-fourth and one-half of their individual MICs, respectively, reduced bacterial counts by greater than 5 log CFU . The postantibiotic effect of clarithromycin combined with 14-hydroxy-clarithromycin was twice that of clarithromycin when tested alone . When orally administered to gerbils with H . influenzae otitis media, the 14-hydroxy metabolite was significantly more active than clarithromycin in reducing bacterial counts from the middle ear . The in vivo activity of the two compounds in combination was synergistic or additive, depending on the level of H . influenzae present at the time treatment was initiated . Significant reductions in bacterial counts and increases in cure rates were observed when clarithromycin at 50 or 100 mg/kg of body weight was combined with 14-hydroxy-clarithromycin at 12 mg/kg or higher . Results from in vitro and in vivo combinations suggest that routine susceptibility tests and animal efficacy studies with clarithromycin alone may underestimate its potential efficacy against H . influenzae.

Indian J Pathol Microbiol, 1990 Jul, 33(3), 239 - 43
Counter immuno electrophoresis for the early diagnosis of acute pyogenic meningitis; Dasgupta J et al.; A total of 123 cases of acute pyogenic meningitis were studied to investigate whether counter current immunoelectrophoresis (CIEP) would facilitate rapid etiological diagnosis when used with other routine methods in a clinical bacteriology laboratory . Of the 123 cases, 53 (43.08 percent) were culture positive . Streptococcus pneumoniae was the commonest etiological agent accounting for 30 (56.6 percent) of the isolates . There were four isolates of Haemophilus influenzae and one of Neisseria meningitidis . High rates of isolation were found from turbid CSF samples, those showing a high polymorphonuclear cellular reaction and from those with a high protein and a low sugar level . CIEP detected antigen in 50 percent of cases of Haemophilus influenzae and 76.7 percent of cases of Streptococcus pneumoniae.

Diagn Microbiol Infect Dis, 1990 Jul-Aug, 13(4), 349 - 52
In vitro activity of BAY v 3522, a new oral cephalosporin tested against Haemophilus influenzae and Branhamella catarrhalis; Doern GV et al.; The in vitro activity of BAY v 3522, a new orally absorbed cephalosporin, was assessed against 150 clinical isolates each of Haemophilus influenzae and Branhamella catarrhalis . The MIC90S for beta-lactamase-positive and -negative strains of H . influenzae were 8 and 2 micrograms/ml, respectively . For beta-lactamase-positive and -negative strains of B . catarrhalis, the BAY v 3522 MIC90S were 4 and 0.25 micrograms/ml, respectively . In general, BAY v 3522 was less active against H . influenzae than amoxicillin/clavulanic acid and cefixime, equivalent in activity to cefuroxime, and more active than cefaclor . BAY v 3522 had activity most similar to cefuroxime and cefaclor for B . catarrhalis but was less active than amoxicillin/clavulanic acid and cefixime.

Pediatrics, 1990 Jul, 86(1), 102 - 7
Serologic responses to an Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in very young Gambian infants; Campbell H et al.; Recent studies in the United States and Europe have shown that Haemophilus influenzae type b polysaccharide-protein conjugate vaccines can induce protective antibody levels in young infants, but it was not clear that this would be the case in African infants, to whom H influenzae vaccines must be given at a very early age to prevent disease caused by H influenzae . Therefore, antibody responses to an H influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine were measured in very young Gambian infants . In the first group (n = 85), to whom the vaccine was given at the ages of 1 and 3 months, the geometric mean antibody level rose from a prevaccination level of 0.23 microgram/mL to a postvaccination level of 1.27 micrograms/mL, and in the second group (n = 56), vaccinated at the ages of 2 and 4 months, the prevaccination level of 0.16 microgram/mL rose to a postvaccination level of 1.59 micrograms/mL . These two final postvaccination levels did not differ significantly, and interpolation suggests that similar antibody levels were present in both groups of infants at the age of 3 months . This is the age by which protection would need to be achieved to protect against H influenzae meningitis in The Gambia and in other countries where the infection has similar epidemiologic characteristics . No significant side effects of vaccination were noted.

Rev Argent Microbiol, 1990 Jul-Sep, 22(3), 115 - 22
{Haemophilus influenzae type B: subtyping of strains isolated from respiratory infections using the outer membrane protein profiles}; Catalano M et al.; Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) applied to outer membrane protein (OMP), extracted by a micromethod, was employed to subtype H . influenza b type I . A total of 37 H . influenzae b strains were isolated from children under 4 years of age, either with lower acute respiratory infection (LARI), or asymptomatic carriers matched according sex, socioeconomic level and seasonality . Twenty seven out of the 37 H . influenzae b strains belonged to biotype I . On the basis of OMP profiles, these 27 were classified into 8 subtypes (Figs . 2, 3, 4 and 5) . The probability of two randomly chosen isolates having different OMP profiles was 0.733 . The subtype termed "a" showed the greatest relative frequency and was detected both in invasive strains and in those isolated from throat samples of LARI cases and healthy children . The use of 14% SDS-PAGE allowed de detection either of a 51kD or a 49kD, as well as 25-40kD proteins, in a single run (Fig . 1) . Most subtype profiles showed the 51 kD protein . Growth conditions and extraction of OMPs by our modified micromethod provide a single and inexpensive procedure within the means of the average clinical laboratory . Besides, this test is much less time-consuming than classical assays . Jointly, biotyping , serotyping and OMP profile determination, proved a useful epidemiological tool to survey H . influenzae b infection.

Plucne Bolesti, 1990 Jul-Dec, 42(3-4), 188 - 90
{Use of Runac in patients with infections of the lower respiratory tract}; Popovac D et al.; Thirty patients went through the outpatient treatment . Causative agent was established in sputum, throat and nose smears of 26 patients . Streptococcus pneumoniae (56%) and Haemophilus influenze (30%) are mostly isolated . Good effects of the medicine is characteristic by quick withdrawal of the symptoms characteristic for respiratory tract infections (cough and expectoration, febrility, physical finding) as well as by debacillosis after 10 days therapy . The effective result of medicine has been particularly noticed through quick reduction until complete disappearance of expectoration after three to four days since the onset of treatment . No side effects of the medicine have been found.

Int J STD AIDS, 1990 Jul, 1(4), 282 - 4
Soluble interleukin-2 receptors in serum and urine of patients with chancroid and their response to therapy; Abeck D et al.; To investigate cell-mediated immune response in chancroid, soluble interleukin-2 receptor levels in serum and urine samples of healthy individuals and patients were measured by an enzyme-linked immunosorbent assay . Increased levels both in serum and in urine were observed in cases of Haemophilus ducreyi infection . In patients showing a prolonged incubation period, urine levels exceeded serum values . Therapy led to a reduction of elevated interleukin-2 receptor levels in serum and in urine.

Diagn Microbiol Infect Dis, 1990 Jul-Aug, 13(4), 341 - 4
Antimicrobial susceptibility of clinical isolates of Haemophilus influenzae to ampicillin-sulbactam; Mortensen JE et al.; A total of 1092 clinical isolates of Haemophilus influenzae (306 type b; 786 non-type-b), from five medical centers were obtained during 1987 and 1988 . Disk diffusion antimicrobial susceptibilities were obtained for all isolates, and broth microdilution susceptibilities were obtained for 502 isolates . Beta-lactamase was produced by 34.3% of type-b and 22.1% of non-type-b isolates, with some geographic variations . Using disk diffusion antimicrobial susceptibility testing, all isolates were susceptible to ampicillin-sulbactam, ceftriaxone, cefuroxime, and rifampin; two isolates were resistant to chloramphenicol . Whether tested using a fixed ratio of ampicillin to sulbactam of 2:1 or a fixed concentration of sulbactam, the ampicillin-sulbactam combination demonstrated good activity against clinical isolates of H . influenzae . Only 8 of the 1092 isolates did not produce beta-lactamase but demonstrated MICs of greater than or equal to 2 micrograms/ml for ampicillin.

Infect Immun, 1990 Jul, 58(7), 2252 - 7
Conserved and nonconserved epitopes among Haemophilus influenzae type b pili; Gilsdorf JR et al.; We investigated the binding of antibodies raised against four different Haemophilus influenzae type b (Hib) plus antigen preparations to the native pili and denatured pilins of 21 Hib isolates . Antibodies against live piliated Hib M43p+, adsorbed with a nonpiliated variant to remove nonpilus antibodies, bound to 18 of the 21 piliated Hib isolates in immunodot assays but failed to recognize the denatured pilins from any of the strains in Western immunoblot assays . Similarly, antibodies against purified native pili of strain E1ap+ bound to 11 of 21 piliated strains in immunodot assays but to only 2 of 21 piliated strains in Western blot assays . The native pili of all 21 strains were recognized by one or both of the antisera . These observations suggest that the immunodominant epitopes of native Hib pili are dependent on conformation and are moderately conserved . In contrast, antibodies against denatured M43p+ pilin or against a peptide derived from amino acids 5 through 17 of M43p+ pilin failed to bind to native pili from any of the 21 piliated isolates on immunodot assay . However, both sera recognized the denatured pilins from all the piliated strains on Western blot assay . These data indicate that the immunodominant epitopes of denatured pilins are highly conserved among different strains of Hib but are unavailable on intact pili for antibody binding.

Presse Med, 1990 Jun 23, 19(25), 1177 - 81
{Arterial embolism of the limbs in infectious endocarditis of the heart valves}; de Gennes C et al.; Nine cases of infective endocarditis (IE) on native valves, complicated by arterial embolism of the limbs (AEL), were collected between June 1974 and October 1988 (prevalence 4.3 percent) . Among the 11 AEL recorded, 9 involved the lower limbs and 2 the upper limbs . The diagnosis, suspected in patients with acute ischaemia (n = 6), transient (n = 1) or pseudophlebitic (n = 1) pain, or discovered by systematic pulse examination (n = 3), was confirmed by Doppler ultrasound (n = 3), angiography (n = 2) or oscillometry (n = 4) . AEL occurred 2.8 weeks on average after the onset of treatment; it appeared 6 months after the end of treatment in 1 case and preceded the diagnosis of IE by 1 to 6 weeks in 3 cases . The causative organisms isolated in 7 cases were: non-haemolytic streptococci (n = 4), Staphylococcus aureus (n = 1), Haemophilus parainfluenzae (n = 1) and enterococcus (n = 1) . Vegetations were found in 6 of the 7 patients explored by echocardiography . Two cases of embolism of the femoral artery required embolectomy . Effective heparin anticoagulation was obtained in only one patient . Six patients underwent valve replacement in the acute phase of endocarditis . After a mean follow-up period of 32 months (range 3 to 120 months), only one patient has symptoms (claudication of the left upper limb); 5 patients are asymptomatic with a reduced (n = 5) or abolished (n = 2) pulse . Three embolisms have left no sequelae . Altogether, AEL are not uncommon in infective endocarditis . They rarely influence the functional prognosis and are detected by systematic palpation of the pulses . Anticoagulation in effective doses is discussed . Attempts at removing the obstruction should be made only in cases with poorly tolerated proximal embolism . In patients with multiple or recurrent embolic accidents, valve replacement may be considered.

Rev Prat, 1990 Jun 11, 40(17), 1551 - 8
{Cystic fibrosis: choices of treatment of respiratory manifestations (except Pseudomonas aeruginosa infections)}; Gilly R et al.; A knowledge of the natural history of cystic fibrosis is the basis for a treatment which, so far, has only been symptomatic . The three fundamental elements of our therapeutic possibilities are: prevention and treatment of bronchial obstruction, administration of antibiotics active against staphylococci and Haemophilus influenza (Pseudomonas aeruginosa infections will be dealt with in another article of this journal), and control of bronchial inflammatory processes . Some complications of cystic fibrosis regarded as serious are no longer beyond our resources . Many works of fundamental research are needed, concerning the local conditions that are necessary to the selective implantation and the development of Staphylococcus aureus in the lung, and the virus Staphylococcus and Staphylococcus-Pseudomonas relations . The real hope of an absolute treatment justifies the new, aggressive therapeutic approach but the precise indications of an antistaphylococcal treatment must still be evaluated carefully . Finally, the complexity of a treatment which must constantly be adjusted is one of the reasons for the existence of "specialized consultations", the organization of which is summarized.

Antimicrob Agents Chemother, 1990 Jun, 34(6), 1079 - 87
Ampicillin killing curve patterns for ampicillin-susceptible nontypeable Haemophilus influenzae strains by the agar dilution plate count method; Woolfrey BF et al.; Ampicillin killing curve patterns for 20 strains of ampicillin-susceptible nontypeable Haemophilus influenzae were determined by the agar dilution plate count method . The paradoxical effect was detected in the 24-h killing curve patterns for each strain . For the biphasic effect, minimum survivor percentages (maximum killing) occurred over a narrow range of ampicillin concentrations immediately above the MIC, with survivor percentages then rising rapidly to peak at approximately 1-log10-unit increment higher . The 24-h minimum survivor percentages for the 20 strains ranged from approximately 0.01% (rapid killing) to greater than 10% (slow killing) . In comparison with the previous results for typeable strains, the present findings suggest that nontypeable stains are, on average, killed much more slowly . Based on the initial 24-h killing curve patterns for the 20 strains, 4 strains were selected as putative representatives of the range of bactericidal responses encountered . These strains were then studied to examine the reproducibility of the 24-h patterns and to determine sequential killing curves . These patterns were found to be reproducible and served to characterize the relative killing responses of the strains . In the sequential studies of three of the four strains, tiny colonies having the gross and microscopic characteristics of L-forms were found to be present on the agar dilution plate count plates prior to the application of penicillinase at 48 and 72 h . Such colonies reverted to vegetative forms within 24 to 48 h after application of penicillinase to the panels . Of particular interest was the observation that the paradoxical effect was manifested both by the L-form colonies and by the reverted vegetative colonies . The late development of L-forms was observed for both rapidly and slowly killed strains.

Acta Paediatr Scand, 1990 Jun-Jul, 79(6-7), 587 - 92
Epidemiology of Haemophilus influenzae type b infections among children in Denmark in 1985 and 1986; Kristensen K et al.; A retrospective epidemiological study of invasive Haemophilus influenzae type b infections among children in Denmark 1985 and 1986 was carried out and 226 cases were identified . Of these 93% occurred in patients younger than five, corresponding to an annual incidence of 40 cases per 100,000 children aged 0-4 years, 68% occurred in patients younger than two years of age, and 6% in patients younger than six months . The annual incidences of meningitis and epiglottis were 27 and 8 cases, respectively, per 100,000 children aged 0-4 years . Of the 156 cases with meningitis four patients died and seven had severe neurological sequelae . Only 67% of the cases of meningitis had been notified.

Nippon Juigaku Zasshi, 1990 Jun, 52(3), 533 - 42
Production and characterization of monoclonal antibodies against Actinobacillus (Haemophilus) pleuropneumoniae serotype 2; Nakai T et al.; Four hybridoma cell lines producing monoclonal antibodies (MAbs) against Actinobacillus (Haemophilus) pleuropneumoniae were established by fusion of mouse myeloma and spleen cells obtained from mice immunized with a serotype 2, strain SH-15 . Enzyme-linked immunosorbent assay-inhibition tests with antigens obtained from 12 serotype strains of A . pleuropneumoniae and 9 other gram-negative bacteria showed that all the MAbs bound to only serotype 2 strains of A . pleuropneumoniae . The epitopes recognized by the MAbs were located on a carbohydrate moiety of lipopolysaccharide (LPS) of the organism, which was sensitive to periodate oxidation . In immunoblotting analyses of LPS obtained from A . pleuropneumoniae serotype 2, all the four MAbs reacted specifically with the characteristic ladder bands of LPS detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . These results suggest that O-antigen side chains of the LPS are one of the antigenic determinants responsible for the serotype-specificity of A . pleuropneumoniae.

J Gen Microbiol, 1990 Jun, 136 ( Pt 6), 1031 - 5
Naturally occurring NAD-independent Haemophilus parainfluenzae; Gromkova R et al.; Four, NAD-independent, clinical isolates of Haemophilus parainfluenzae were recovered from a genital ulcer, a purulent skin lesion, a sputum specimen and a throat swab respectively . With the exception of NAD requirement, the strains exhibited the biochemical characteristics of H . parainfluenzae biotype II . The genetic relationship between these isolates and a standard strain of H . parainfluenzae was determined by testing transforming activities of two chromosomal markers, streptomycin resistance and nalidixic acid resistance . The clinical isolates were efficient donors and recipients in transformation . In addition, we demonstrated transfer of the genes conferring NAD independence to typical, NAD-requiring H . parainfluenzae and Haemophilus influenzae strains.

J Chemother, 1990 Jun, 2(3), 182 - 4
Clindamycin in the treatment of an outbreak of streptococcal pharyngitis in a kibbutz due to beta-lactamase producing organisms; Raz R et al.; During the winter of 1987-88, an epidemic of streptococcal pharyngitis (SP) affected almost 25% of the 800 inhabitants of a community settlement (kibbutz), and failed to respond to treatment with penicillin and/or erythromycin, despite the fact that the streptococci were highly sensitive to penicillin (minimum inhibitory concentration: MIC less than 0.001 micrograms/ml) . We suggested that the concomitant presence of beta-lactamase producing organisms in the pharyngeal cavities of the affected individuals with SP could inactivate the antibiotics, rendering the streptococci resistant to penicillin . Throat swabs were taken and tested for aerobic and anaerobic beta-lactamase producing organisms and for beta-lactamase activity and clindamycin treatment was given to 110 patients with SP . Beta-lactamase activity was detected in 90 cases and the cultures were positive for Staphylococcus aureus (25 cases), Haemophilus sp . (22 cases) and anaerobes, which we did not identify in 68 cases . Ninety-eight patients completed the ten-day course of treatment with clindamycin and 96 were cured clinically and bacteriologically . The epidemic was controlled.

Can J Vet Res, 1990 Jun, 54(3), 331 - 6
Epidemiology of Haemophilus somnus in young rams; Lees VW et al.; The prevalence of Haemophilus somnus in the prepuce of young rams was examined . Of 473 rams entering Record of Performance (ROP) stations at 50 days of age, 43 (9.1%) were positive . Average daily gain was not affected by Haemophilus status, but was influenced by breed of ram . Suffolks were predicted to gain 0.515 kg daily compared to 0.427 kg for a group combining all other breeds . Using logistic regression to identify risk factors for individual H . somnus infection, rams in 1989 were 0.382 times as likely to be infected as rams in 1988, and Suffolks were 0.314 times as likely to be infected as the other breeds group, but these factors were not significant at the flock level . Of 80 eligible flocks of origin, 22 (27.5%) were classified as infected with H . somnus, based on rams submitted to the ROP station . Infected flocks contributed 133 rams, 43 (32.3%) of which were positive . There was no association between H . somnus status and lambing percent of the percent of abortions and stillbirths, but there was a statistically significant association with the percent of ewes which failed to lamb . In the model developed, 6% of the bred ewes in noninfected flocks failed to lamb, compared to a rate of 12% in infected flocks . These results suggest H . somnus may influence ewe fertility earlier, rather than later in gestation . Purchasing replacement animals and having cattle on the farm were risk factors for Haemophilus infection in the flock . Where replacements had been purchased within the previous year, the risk of flock infection rose 8.5 times, and on farms having cattle as well as sheep, the risk rose 13.2 times.(ABSTRACT TRUNCATED AT 250 WORDS)

Can J Vet Res, 1990 Jun, 54(3), 326 - 30
The protective effect of vaccination against experimental pneumonia in cattle with Haemophilus somnus outer membrane antigens and interference by lipopolysaccharide; Silva SV et al.; A semi-purified outer membrane anionic antigen (AA) fraction was isolated from Haemophilus somnus by a modified procedure of anion exchange chromatography to yield a protein fraction free of lipopolysaccharides (LPS) . The AA fraction (1 mg) was administered with or without the homologous lipopolysaccharide (10 micrograms/kg body weight) as vaccines to groups of cattle twice, three weeks apart . A control group which did not receive any antigen was included in the trial . Six weeks after the first vaccination, the animals were challenged intratracheally with a virulent pneumonic strain of H . somnus (70986) and observed for clinical signs of respiratory disease . The cattle were euthanized six days later and the lungs were evaluated for the severity of lesions macroscopically as well as histopathologically . Vaccination with AA alone provided the best protection against pneumonia as indicated by significantly lower clinical scores, less extensive gross lung lesions and mild histopathological lesions with immune cell infiltration . However, when AA was combined with LPS in the vaccination, this protective effect was negated and the animals showed more detrimental histopathological lesions than the controls.

Can J Vet Res, 1990 Jun, 54(3), 320 - 5
Capsular polysaccharide antigens for detection of serotype-specific antibodies to Actinobacillus pleuropneumoniae; Bosse JT et al.; Capsular polysaccharides (CPS) of serotypes 1, 2, 5 and 7 of Actinobacillus (Haemophilus) pleuropneumoniae were obtained from 18 h culture supernatants by precipitation with hexadecyltrimethyl-ammonium bromide (Cetavlon) followed by extraction with sodium chloride and reprecipitation in ethanol . These crude extracts, and portions purified further by phenol extraction to remove contaminating proteins, were evaluated as antigens for the detection of serotype-specific antibodies to A . pleuropneumoniae in sera from immunized rabbits and swine by an enzyme-linked immunosorbent assay . The crude extracts reacted strongly with homologous antisera, but except for serotype 1 showed considerable cross-reactivity with antisera to other serotypes . Phenol extraction greatly improved the serospecificity of the antigens from serotypes 1, 7 and, to a lesser extent, 5 . The serotype 2 CPS antigen showed poor reactivity following phenol extraction, and did not appear as useful for detection of serotype-specific antibodies.

Eur J Pediatr, 1990 Jun, 149(9), 613 - 4
Haemophilus influenzae osteomyelitis complicating dactylitis in homozygous sickle cell disease; Webb DK et al.; A case of Haemophilus influenzae osteomyelitis complicating dactylitis in homozygous sickle cell disease is described . It is the first description of this association to our knowledge, and resulted in permanent damage and shortening of all affected bones.

Ann Thorac Surg, 1990 Jun, 49(6), 940 - 6; discussion 946-7
Role of lung decortication in symptomatic empyemas in children; Gustafson RA et al.; Despite appropriate antibiotics and pleural drainage, the condition of some children with empyema fails to improve . In a 5-year period, 10 children ranging in age from 2 to 16 years underwent lung decortication for a refractory, symptomatic empyema, which had developed 3 to 5 weeks after an initial pneumonic infiltrate . Responsible organisms included beta-hemolytic streptococci, Haemophilus influenzae, or Streptococcus pneumoniae in 6 children . Negative cultures were found in 4 children . The initial computed tomographic scan of the chest in 4 of 8 patients showed more than 75% limitation of lung expansion by the contents of the empyema cavity . In 4 other patients, an extensive pleural peel was seen on initial computed tomographic scan of the chest . Several studies also showed cystic lesions in the collapsed lung . Multiple computed tomographic scans in 3 patients confirmed the lack of clinical and chest roentgenographic improvement with conservative therapy . At decortication in each, the visceral and parietal pleural peel was completely removed, freeing the trapped lung . Two patients also had a concomitant lobectomy for a necrotic right upper lobe (1 patient) and left lower lobe (1) . Clinical improvement was marked, with return of temperature, white blood cell count, and appetite to normal . Postoperative morbidity was minimal . Analysis of these patients in whom traditional conservative therapy failed suggested that the initial management during the early exudative phase was often delayed and was not aggressive enough from the standpoint of pleural drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Mutat Res, 1990 Jun, 244(2), 141 - 5
Mutagenic and lethal action of polychromatic near-ultraviolet (325-400 nm) on Haemophilus influenzae in the presence of nitrogen; Cabrera-Juarez E et al.; The lethal effect of polychromatic near-UV light (325-400 nm) on Haemophilus influenzae was 8 times higher under aerobic than anaerobic irradiation . This light increased the frequency of mutation to novobiocin resistance and ability to utilize protoporphyrin IX . The slope of mutagenic effect at low doses appeared greater for the aerobic than for the anaerobic group . We concluded that polychromatic near-UV mutation of H . influenzae under anaerobic irradiation was caused by direct oxygen-independent action on DNA.

J Otolaryngol, 1990 Jun, 19(3), 179 - 81
Adult supraglottitis due to herpes simplex virus; D'Angelo AJ Jr et al.; Changes in the concepts regarding epiglottis have occurred over the last two decades . Supraglottis, once thought to occur exclusively in the pediatric population, is now recognized in adults . Supraglottis is a well-defined syndrome usually caused by a bacterial infection by Haemophilus influenzae type B . Recently, other organisms have been implicated as etiologic agents in cases of supraglottitis . Documented viral supraglottitis is very rare, and adult supraglottitis due to herpes simplex virus-I has not been reported to our knowledge.

J Infect Dis, 1990 Jun, 161(6), 1210 - 5
The epidemiology of Haemophilus influenzae meningitis in children under five years of age in The Gambia, West Africa; Bijlmer HA et al.; Haemophilus influenzae meningitis was studied over a 2-year period in children less than 5 years of age in a population-based, prospective study in The Gambia, West Africa . A total of 77 cases were recorded . The incidence was 60 cases/100,000 children less than 5 years of age and 297 cases/100,000 children less than 1 year of age . The peak prevalence was at the age of 5 months; 83% of the children were less than 1 year old and 45% were less than 6 months old . Only 55% of cases recovered completely . The distance to the nearest hospital was an important predisposing factor for a fatal outcome . Two cases were secondary . Many patients were anemic and underweight . The observations show that H . influenzae meningitis in The Gambia has an incidence as high as that in the USA, but that it has 10-fold more devastating outcome . If the infection is to be prevented by vaccination in The Gambia, immunization will have to be given very early in life.

Infect Immun, 1990 Jun, 58(6), 1600 - 5
Haemocin, the bacteriocin produced by Haemophilus influenzae: species distribution and role in colonization; LiPuma JJ et al.; Four hundred thirty-eight strains of Haemophilus influenzae were examined for production of and sensitivity to haemocin, a bacteriocin produced by some members of this species . Whereas 199 of 212 (94%) type b isolates produced haemocin, 131 of 134 (98%) nontypeable and 91 of 92 (99%) encapsulated non-type b isolates were sensitive to haemocin . Among strains previously genetically characterized by multilocus enzyme electrophoresis, haemocin production was detected in type b isolates belonging to 25 of 29 (86%) clonally distinct electrophoretic types . None of 60 clonally distinct nontypeable strains produced this substance, and all were sensitive to it in vitro . The genes encoding haemocin production were transformed independently of the genes necessary for capsule expression from a prototypic type b strain to a nontypeable strain . After intranasal inoculation of infant rats with an equal mixture of a non-haemocin-producing strain and its haemocin-producing transformant, organisms capable of haemocin production predominated in both nasopharyngeal and blood cultures . These data demonstrate that haemocin production is strongly associated with type b encapsulated members of this species and suggest a mechanism by which haemocin might play a role in host nasopharyngeal colonization by this pathogen.

Southeast Asian J Trop Med Public Health, 1990 Jun, 21(2), 195 - 202
Haemophilus influenzae and Streptococcus pneumoniae in children with acute respiratory infection; Jayanetra P et al.; The incidence of Haemophilus influenzae and Streptococcus pneumoniae in children with acute respiratory infection (ARI) under 5 years was carried out by throat swab culture, blood culture, body fluid or tissue culture in 688 patients from a community, 744 patients from a teaching hospital in Bangkok, 766 normal children from the community and 303 children from a hospital well baby clinic . H . influenzae was found in the throats of 15-20% of patients and in the throats of 4-6% of normal children (p less than 0.001 for both hospital and community patients) . Only 12/332 strains (3.6%) of H . influenzae were type b . The rest of H . influenzae were non type b . The most common biotype of H . influenzae non type b was biotype II . S . pneumoniae was found in hospital patients in highly significant numbers compared to the controls (12% vs 4%) . No significant difference was observed in strains from the community patients.

Southeast Asian J Trop Med Public Health, 1990 Jun, 21(2), 185 - 93
Drug resistance of Haemophilus ducreyi; Rutanarugsa A et al.; Chancroid, the disease caused by H . ducreyi is one of the common sexually transmitted diseases (STD) in Thailand and other tropical countries . In Thailand, the diagnosis of chancroid is still based on clinical appearance which may be confused with other STD manifested by genital ulcers . In recent years the increasing resistance strains of H . ducreyi to these antimicrobial agents has been reported so that cultivation and antimicrobial susceptibility tests of this organism have become more important . This study showed that MBV is the best medium for isolation with a success rate of 48% . All strains tested from isolates of this study were resistant to ampicillin, due to production of beta-lactamase . Approximately 99% of the strains were resistant to tetracycline 92% of strains were resistant to sulfamethoxazole and 32% were resistant to trimethoprim . All isolates were susceptible to chloramphenicol, ceftriaxone, erythromycin and the fluorinated quinolones ciprofloxacin, norfloxacin, ofloxacin and pefloxacin . Beta-lactamase enzymes produced by 37 strains of H . ducreyi were determined for their isoelectric point (pI) . All had pI of 5.4, indicative of plasmid-mediated beta-lactamase type TEM-1.

Jpn J Antibiot, 1990 Jun, 43(6), 1164 - 73
{A clinical study on ceftazidime in the treatment of intractable respiratory infections}; Miyatake H et al.; Ceftazidime (CAZ) was administered to 51 patients (37 males, 14 females) with respiratory infections including severe cases, accompanied by various underlying respiratory diseases . The clinical efficacy and side effects of CAZ were investigated . The mean age and body weight of these 51 cases were 62.6 years and 48.0 kg, respectively . CAZ was administered by intravenous drip infusion (daily dose of 2-4 g) for a mean of 14.7 days to a mean total dose of 56.7 g . Clinical efficacy rates were 64% (18 of 28 cases), 80% (16 of 20 cases) and 67% (2 of 3 cases) for airway and intermediary regional infections, pneumonia (including lung abscess) and pyothorax, respectively . In the bacteriological study, efficacy rates and bacterial eradication rates were 69% and 67%, 33% and 20%, 100% and 100%, and 100% and 100% for infections caused by Pseudomonas aeruginosa (13 cases), Staphylococcus aureus (6 cases), Streptococcus pneumoniae (6 cases) and Klebsiella pneumoniae (4 cases), respectively, and bacterial eradication was achieved in both of 2 cases of Peptostreptococcus anaerobius and 2 cases of Haemophilus influenzae, and 1 case each of Peptococcus sp., Fusobacterium necrophorum and Serratia marcescens . Side effects observed were eruption in 1 case (2%) and elevated GOT, GPT and Al-P values in 1 case (2%), but these cases tended to recover after CAZ treatment was discontinued.

Semin Dermatol, 1990 Jun, 9(2), 105 - 8
The epidemiology of sexually transmitted diseases in Africa and Latin America; Goeman J et al.; We review some aspects of the epidemiology of sexually transmitted diseases (STDs) in the developing countries of Africa and Latin America . Apart from their elevated prevalence, they are responsible for important morbidity in mother and child . Stillbirth, premature delivery, conjunctivitis, and respiratory tract morbidity of the neonate are frequently caused by STDs . Sequelae in adult women include pelvic inflammatory disease, ectopic pregnancy, and infertility . The emergence of antimicrobial resistance has complicated the picture in recent times . Genital ulcer disease is very common in developing countries, the most important being chancroid . Both continents are experiencing major epidemics of the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection with different epidemiological characteristics than in the industrialized world . A link might exist between the high prevalence of STDs and the rapid heterosexual spread of HIV infectionPIP: Aspects of sexually transmitted diseases (STDS) peculiar to the developing countries in South America and sub-Saharan Africa are discussed . The most common STD infections are N . Gonorrhoeae, Chlamydia trachomatis, T . pallidum and T . vaginalis . Vertical transmission, particularly of syphilis among prostitutes, and of Chlamydia and gonorrhea after ophthalmia neonatorum, are common . Chlamydia is also a common respiratory tract infection in African neonates . Late complications of STDs, infertility and ectopic pregnancy, and particularly pelvic inflammatory disease, are responsible for a high proportion of hospitalizations . Antibiotic resistant gonorrhea strains are common, a result of poorly managed antibiotic treatment . Genital ulcer diseases (GUD), which predispose to HIV infections, are more common in Africa than in developed countries, not only herpes but chancroid, donovanosis and lymphogranuloma venereum . Chancroid, caused by Haemophilus ducreyi, causes 36-49% of ulcers in 2 reports . The L1-L3 strains of Chlamydia trachomatis cause lymphogranuloma venereum, the agent responsible for ulcers in 3.6-6.1% of 2 clinic populations . HIV infections have an equal sex ratio in Africa, with a younger age incidence in women and a high vertical transmission rate, while in Latin America, bisexual men, and increasingly, heterosexual transmission by intravenous drug users is reported . There is also an HIV-2 virus, whose virulence is in question, common in West Africa .

Pathol Biol (Paris), 1990 Jun, 38(5 ( Pt 2)), 517 - 20
{Randomized study of cefatrizine versus cefaclor in conjunctivitis otitis syndrome}; Cohen R et al.; The association conjunctivitis-otitis is highly suggestive of Haemophilus influenzae infection . This conjunctivitis otitis syndrome could be a good model to assess the efficacy of different antibiotic regimen in the treatment of acute otitis media due to HI without tympanocentesis . This prospective randomized trial compared the efficacy of two orally cephalosporins which demonstrate in vitro an activity against HI . This study was conducted from 4.20.1988 to 3.15.1989 and involved 73 children with COS examined in an outpatient clinic . The mean age was 17.7 months . Before treatment culture were taken from the lower palpebral conjunctivae . 81 strains was found: HI 61 (beta-lactamase-producing 15), Streptococcus pneumoniae 16, Branhamella Catarrhalis 4 . The 73 patients were treated with 40 to 50 mg/kg/day of the test drug for ten days, 25 with Cefaclor in 3 divided dose (group 1), 24 with Cefatrizine in 3 divided dose (group 2), 24 with Cefatrizine in 2 divided dose (group 3) . The recoveries was obtained in 17/25 in the group 1, 18/24 in the group 2, 15/24 in the group 3 . There was no significant difference between the 3 groups.

J Clin Microbiol, 1990 Jun, 28(6), 1185 - 7
Proposal of a new serovar and altered nomenclature for Haemophilus paragallinarum in the Kume hemagglutinin scheme; Blackall PJ et al.; By using the Kume hemagglutinin serotyping scheme, 13 Australian isolates of Haemophilus paragallinarum were shown to constitute a new serovar within the presently termed serogroup II . Because of the likelihood that new serovars will continue to be established, we propose a rationalization of the nomenclature of the Kume scheme . Under this altered scheme, the three recognized serogroups I, II, and III are renamed A, C, and B, respectively . Within each of the serogroups, the serovars are numbered sequentially, allowing new serovars to be added in numerical order . Thus, the nine currently recognized Kume serovars are termed A-1, A-2, A-3, A-4, B-1, C-1, C-2, C-3, and C-4.

Clin Exp Immunol, 1990 Jun, 80(3), 304 - 13
Beneficial effects of the thymic hormone preparation thymostimulin in patients with defects in cell-mediated immunity and chronic purulent rhinosinusitis . A double-blind cross-over trial on improvements in monocyte polarization and clinical effects; Tas M et al.; Twenty patients with chronic purulent rhinosinusitis were treated with TP-1 (Serono; 1 mg/kg body weight), in a double-blind cross-over trial . TP-1 was administered by daily i.m . injections for the first 14 days followed by two injections/week for 6 further weeks . The patients were immunologically special in that they had defects in their cell-mediated immune system . Fourteen showed a decreased chemotactic responsiveness of their peripheral blood monocytes as measured in the polarization assay . This defective function can probably be ascribed to the presence in serum of low molecular weight factors (LMWFs; less than 25 kD) . As reported earlier, this factor shows a structural homology to the envelope protein of murine and feline leukaemia virus (P15E) . Thirteen patients showed a defective delayed-type hypersensitivity (DTH) skin test reactivity towards candidin and/or streptokinase-streptodornase (Sk/Sd) antigen, 14 had a defective MIF production from their peripheral blood lymphocytes towards candidin, Sk/Sd and/or Haemophilus influenzae antigen . Eighteen patients completed the TP-1 trial and showed clinical improvements: 12 out of 15 were feeling better during TP-1 therapy and the nasal mucosa showed on inspection absent mucopurulent secretion in 13 patients . Positive bacterial culture rates for the nose decreased from 14 out of 16 to five out of 15 . Placebo treatment had no significant effects . The clinical improvements were accompanied by a better performance of the cell-mediated immune system; the most significant effects were recorded in the monocyte polarization assay . The suppressive P15E-like LMWFs in serum clearly decreased during TP-1 treatment . In vitro TP-1 neutralized the immunosuppressive effect of the LMWFs . The restoring effects of TP-1 on monocyte polarization and its neutralizing activity of P15E-like LMWFs could explain the beneficial effects of thymic hormone treatment reported in adults with clinical signs of immunodeficiency in the presence of a full T cell repertoire.

Am J Infect Control, 1990 Jun, 18(3), 160 - 6
Invasive Haemophilus influenzae type B infections: a continuing challenge; Janai H et al.; Invasive Haemophilus influenzae type b infections are a major cause of severe infections in children between 2 months and 5 years of age . Meningitis, arthritis, pneumonia, cellulitis, osteomyelitis, and epiglottitis affect approximately 25,000 patients annually and are a major cause of mortality and morbidity in children . H . influenzae type b clinical syndromes, diagnostic methods, epidemiology, immunity, and treatment are discussed in this review . Although potent antibiotics have long been available for treatment, mortality and morbidity rates have not declined substantially in the last 15 years . Prevention of disease is therefore a continuous medical challenge . Secondary cases can be prevented by identification of the high-risk groups and the application of appropriate techniques, including antimicrobial prophylaxis . Primary prevention is the major goal of current research . H . influenzae type b vaccines currently are available for protection of infants 18 months of age and older . Prevention of primary and secondary disease and future developments, including new vaccine strategies, are stressed.

J Otolaryngol, 1990 Jun, 19(3), 169 - 74
Haemophilus influenzae type B and its role in diseases of the head and neck; Halperin SA; Haemophilus influenzae is a common pathogen in infections of the head and neck . Although most mucosal infections (otitis media, sinusitis) are caused by non-encapsulated organisms, invasive disease (meningitis, periorbital cellulitis, epiglottis) is caused by type B encapsulated organisms . Bacteremia is common with H . influenzae type B infections and therapy with parenteral antibiotics is indicated . A vaccine against H . influenzae type B given at 18 months of age is now part of the routine childhood immunization schedule . Chemoprophylaxis with rifampin is recommended for at-risk contacts of patients with invasive type B disease . This review examines the bacteriology, pathogenesis, immunity, and disease manifestations of H . influenzae . Appropriate diagnostic methods, antimicrobial therapy, and recommended chemoprophylaxis and immunoprophylaxis are presented.

Pediatr Clin North Am, 1990 Jun, 37(3), 735 - 56
Vaccine-preventable disease and immunization in the developing world; Bart KJ et al.; Vaccines have given health care providers control over a substantial portion of the morbidity and mortality in the developing world . Global efforts have immunized two-thirds of the world's children with DTP and polio vaccines; 72% have received BCG and 59% measles vaccine; but only 29% of pregnant women have received two doses of tetanus toxoid . In addition, vaccines against yellow fever, Japanese encephalitis, hepatitis B, rubella, and mumps and meningococcal polysaccharide vaccine are being used in specific regions of the world . New vaccine candidates will enhance the vaccine armamentarium over the next decade to include the causes of pneumonia, diarrhea, and meningitis: Haemophilus influenzae type b, pneumococcal and meningococcal protein conjugate vaccines, typhoid and rotavirus vaccine . Genetically engineered vaccine vehicles, genetic reassortants, and genetic deletions are being investigated as new vaccine candidates.

Pediatr Clin North Am, 1990 Jun, 37(3), 567 - 83
New vaccines against Haemophilus influenzae type b; Shapiro ED; Recently, great progress has been made in the development of vaccines against Hib . Four polysaccharide-protein conjugate vaccines are actively being tested . Three of these (PRP-D, HbOC, and PRP-OMP) are currently licensed for use in children at 15-18 months of age . Clinical trials of these vaccines in infants are currently being conducted in the United States . If these show the vaccines to be efficacious, licensure for infants will follow . Although much work remains to be done, it seems likely that the effective prevention of serious Hib infections in infants, as well as in older children, is a goal that may be within our reach in the next several years.

J Pediatr, 1990 Jun, 116(6), 991 - 6
Medical management of chronic suppurative otitis media without cholesteatoma in children; Fliss DM et al.; To determine whether systemic administration of antibiotics may eliminate or reduce the need for tympanomastoid surgery in chronic suppurative otitis media without cholesteatoma, we undertook a randomized, prospective study comparing three regimens: (1) daily suction and debridement, with intravenous administration of mezlocillin until 3 days after the discharge stopped, (2) daily suction and debridement, with intravenous use of ceftazidime until 3 days after the discharge stopped, and (3) daily suction and debridement without antibiotics . No topical antimicrobial agents were used during the study . Fifty-one patients were included, and 48 children completed the study . The duration of discharge from the ear before treatment was 2 to 123 months (median 20 months) . In 26 patients (51%), the disease was bilateral . Aerobic cultures, obtained with the Alden-Senturia middle ear aspirator, yielded Pseudomonas aeruginosa in 98%, enteric gram-negative bacilli in 33%, staphylococci in 25%, and Haemophilus influenzae in 12% . The first 33 patients were randomly assigned to one of the three regimens . In the 21 patients treated with suction and antibiotics (either mezlocillin or ceftazidime), the discharge stopped completely, versus in only 1 (8%) of 12 patients in the suction-only regimen (p less than 0.01) . Therefore the following 18 patients were randomly assigned to one of only two groups, which included the two suction-and-antibiotic regimens . In all patients treated initially with antibiotics, discharge stopped after 4 to 18 days (mean 12.0 days), but 25% needed treatment for greater than 14 days . Amoxicillin prophylaxis was administered to 27 (56%) of the patients after completion of therapy . All patients were followed for 6 months . Drainage recurred in 12 (25%) patients during the first 3 months after the study . The recurrence rate was not affected by the antibiotic regimen, the patient's age, the duration of drainage before initiation of antibiotic therapy, or prophylaxis . We conclude that intravenous wide-spectrum antibiotic therapy in conjunction with daily suction and debridement is efficacious for the treatment of chronic suppurative otitis media without cholesteatoma.

Infect Immun, 1990 Jun, 58(6), 1909 - 13
Expression in Escherichia coli of a high-molecular-weight protective surface antigen found in nontypeable and type b Haemophilus influenzae; Thomas WR et al.; An Escherichia coli clone producing a high-molecular-weight surface antigen of Haemophilus influenzae type b (Hib) was isolated from a library of Hib DNA fragments cloned as lysogens in a lambda replacement vector . The antigen is found in sarcosyl-insoluble outer membrane protein preparations and was produced by all 36 H . influenzae isolates tested . Absorption studies indicated that the antigen is a surface determinant on all isolates tested . Antibodies to the antigen (D15) were found in eight of nine convalescent-phase sera from children with invasive Hib infection . Affinity-purified antibodies prepared against the cloned antigen gave protection against the development of bacteremia in a rat pup model.

Res Microbiol, 1990 Jun, 141(5), 519 - 28
TnA transposons can be introduced and maintained in Neisseria gonorrhoeae; Piffaretti JC et al.; In Neisseria gonorrhoeae, all penicillinase-specifying plasmids isolated so far share homology with each other and carry a 60% deleted sequence of TnA . Plasmid pHD131, an element isolated from Haemophilus ducreyi and carrying an intact copy of the ampicillin resistance transposable element, was introduced from Escherichia coli into N . gonorrhoeae by both transformation and conjugative mobilization . Plasmids were recovered with no detectable deletion . After their transfer back into E . coli, transposition assays onto phage-lambda DNA demonstrated that the TnA elements were still functional . Plasmid pHD131 could be stably maintained in N . gonorrhoeae with or without the presence of penicillin . These results support the hypothesis that the absence in N . gonorrhoeae of plasmids carrying entire and functional TnA transposons cannot be ascribed to incompatibility between the genetic element and the host, but rather to a barrier to introduction of foreign DNA into gonococcus.

Pathol Biol (Paris), 1990 Jun, 38(5 ( Pt 2)), 521 - 5
{Azithromycin versus josamycin: treatment of 89 cases of acute pneumonia}; Aprim et al.; In an open, multicenter randomized clinical trial on patients with acute pneumonia, 5-day therapy using a new oral macrolide antibiotic, azithromycin (Az), was compared with standard 10-day therapy using another macrolide, josamycin (J) . Eighty-nine patients were treated (46 Az, 43 J); both groups were comparable, except in terms of the sex ratios . The causative agent was determined in 31 cases; streptococcal pneumonia was the most common diagnosis (48%) . Cure rates were 93% for J and 80% for Az (p greater than 0.30), as judged by a fall in body temperature and an improvement in clinical condition and in radiographic findings . Among 6 failures, there were 4 cases of empyema (1 J, 3 Az) . Of 6 deaths, 2 were pneumonia-dependent (1 J and 1 Az, Haemophilus and Streptococcus pneumoniae, respectively) . We conclude that 5-day Az is as effective as 10-day J and that such short-course therapy is an advantage in the treatment of pneumonia caused by macrolide susceptible pathogens.

Antimicrob Agents Chemother, 1990 Jun, 34(6), 1041 - 4
Randomized comparative study of cefixime versus cephalexin in acute bacterial exacerbations of chronic bronchitis; Verghese A et al.; Patients with purulent exacerbation of chronic bronchitis were randomized to receive either a single 400-mg daily dose of cefixime or 250 mg of cephalexin, orally, four times a day . Patients were males with a mean age of 63 years . Of the 86 patients, 71 (82%) had bronchitis caused by a single organism (29 by Haemophilus influenzae, 27 by Branhamella catarrhalis, 9 by gram-negative enteric organisms, 6 by Streptococcus pneumoniae), while more than one pathogen was implicated in 15 patients (18%) . A total of 70.8% of the cefixime group and 50% of the cephalexin group were clinically cured (chi 2 = 3.89, P less than 0.05); however, when the categories of cured and improved were combined, no significant difference was noted between treatment groups (chi 2 = 3.39, P = 0.06) . Analysis of side effects included all 130 evaluable and nonevaluable patients: diarrhea was noted in six patients in the cefixime group and none of the patients in the cephalexin group (P = 0.013 by the Fisher exact test) . The diarrhea was mild and self-limited in all cases . B . catarrhalis has emerged as a major cause of exacerbation of bronchitis in our experience; there is an increased need to emphasize the examination of sputum samples by Gram staining if cost-effective antibiotic choices are to be made; any empirically chosen antibiotic should have activity against beta-lactamase-producing strains of B . catarrhalis as well as S . pneumoniae and H . influenzae.

Oral Microbiol Immunol, 1990 Jun, 5(3), 155 - 61
Outer membrane proteins of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus studied by SDS-PAGE and immunoblotting; Bolstad AI et al.; This investigation characterized and compared outer membrane proteins (OMP) of the closely related Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus by means of SDS-PAGE patterns and reactions on immunoblots with rabbit antiserum against A . actinomycetemcomitans FDC Y4 . Reactions with serum from a patient with Papillon Lefevre syndrome (PLS), from whom periodontal wild strains of A . actinomycetemcomitans had been isolated, were also studied . OMP were purified with selective solubilization from lyophilized cells of 10 wild and 4 reference strains of A . actinomycetemcomitans and 4 reference strains of H . aphrophilus . OMP profiles from wild and reference strains of A . actinomycetemcomitans were similar while those from A . actinomycetemcomitans and H . aphrophilus differed . The most prominent difference was absence of a heat modifiable protein in H . aphrophilus strains . Immunoblotting revealed strong common antigens in most strains, including a heat modifiable protein with mol wt 34 kDa, as well as a 29 kDa and a 16.5 kDa protein . Treatment with pronase and sodium periodate confirmed the protein nature of the major OMP antigens.

J Bacteriol, 1990 Jun, 172(6), 3304 - 9
Characterization of repetitive sequences controlling phase variation of Haemophilus influenzae lipopolysaccharide; Weiser JN et al.; Phase variation of lipopolysaccharide epitopes of an Haemophilus influenzae serotype b strain (strain RM.7004) occurs through a mechanism which depends on multiple tandem repeats of the DNA sequence 5'-CAAT-3' situated within the chromosomal locus lic1 . We report here that the same tetranucleotide repeats are also found in two other genomic loci (lic2 and lic3) of RM.7004 . Similar to lic1, there are multiple tandem repeats of 5'-CAAT-3' present at the 5' ends of long open reading frames in lic2 and lic3 . Variation in the number of repeats of CAAT, by shifting the upstream initiation codons in or out of phase with the remainder of the open reading frame, could switch on or off the translation of downstream genes . Similar to previously reported findings for lic1, site-directed mutations in the open reading frame downstream (3') from the repeats of CAAT in lic2 abolished phase variation and identified DNA sequences required for the expression of additional oligosaccharide epitopes . When we used an oligonucleotide comprising five repeats of CAAT or DNA sequences specific for lic1, lic2, and lic3 as probes, a survey of other encapsulated H . influenzae strains (serotypes a through f) and nontypable H . influenzae strains (including biotype aegyptius) showed that the chromosome of H . influenzae can have from two to five regions which contain multiple tandem repeats of CAAT in addition to other sequences which hybridize to lic1 and lic2.

Infect Immun, 1990 Jun, 58(6), 1558 - 64
Cloning and expression in Escherichia coli of a Haemophilus influenzae type b lipooligosaccharide synthesis gene(s) that encodes a 2-keto-3-deoxyoctulosonic acid epitope; Spinola SM et al.; The composition of lipooligosaccharide (LOS) can modify the virulence of Haemophilus influenzae type b (Hib) . A genomic library of Hib strain A2 was constructed in the lambda bacteriophage EMBL3 . Twenty-six phage clones expressed a Hib LOS oligosaccharide epitope in Escherichia coli that was detected by the monoclonal antibody (MAb) 6E4 . None of the clones bound a polyclonal sera specific for Hib A2 LOS or an anti-H . influenzae lipid A MAb . One clone, designated EMBLOS-1, assembled an oligosaccharide with an apparent molecular weight of 1,400 (the 1.4K oligosaccharide) on a 4.1K lipopolysaccharide (LPS) species in E . coli LE392 and produced a novel 5.5K LPS that bound 6E4 . Binding of 6E4 to the 5.5K EMBLOS-1 LPS band was abolished by treatment with sodium metaperiodate but was not affected by digestion with proteinase K, confirming the carbohydrate nature of the epitope . The EMBLOS-1 Haemophilus insert hybridized to similar restriction fragments in type b and nontypeable strains regardless of whether they expressed the 6E4 epitope . The 6E4 epitope did not undergo phase variation in Hib strain A2 at a frequency of greater than 10(-3) . The oligosaccharide of the Salmonella minnesota Re mutant and 2-keto-3-deoxyoctulosonic acid (KDO) inhibited binding of 6E4 to Hib A2 LOS . We conclude that a gene(s) encoding an enzyme(s) that assembles a stable Hib LOS epitope containing KDO is conserved in H . influenzae and that the cloned Hib LOS synthesis gene products assemble a Hib LOS epitope on an E . coli K-12 LPS core.

CMAJ, 1990 May 15, 142(10), 1081 - 5
Rapid control of a chancroid outbreak: implications for Canada; Jessamine PG et al.; From June to November 1987 an outbreak of chancroid occurred in Winnipeg, the first in more than 10 years; 14 people (9 men, 5 women) were involved . Nine of the cases were confirmed through culture . A control strategy was implemented in November 1987 that included presumptive treatment of genital ulcer disease with single-dose antimicrobial therapy, intensive tracing of contacts and treatment of asymptomatic sexual contacts . The origin of the outbreak was not determined, and an epidemiologic link between all the patients could not be demonstrated . The isolates were found to contain the same plasmid; this suggested that a single clone of Haemophilus ducreyi was responsible for the outbreak.

J Immunol, 1990 May 15, 144(10), 3770 - 8
Immunization of humans with polysaccharide vaccines induces systemic, predominantly polymeric IgA2-subclass antibody responses; Tarkowski A et al.; Ig class- and IgA subclass-specific immune responses to protein and polysaccharide Ag were studied in serum, external secretions, and at the single cell level in peripheral blood of systemically immunized adults . Immunization with tetanus toxoid induced predominantly IgG antibody responses in serum and in the PBMC . The IgA antibody response was low, and was mostly of the IgA1 subclass . In contrast, immunization with polysaccharide Ag (Haemophilus influenzae type b, Neisseria meningitidis serogroup A, C, Y, W-135, and Streptococcus pneumoniae capsular polysaccharides) elicited a major IgA response predominantly of the IgA2 isotype . Analysis of the molecular forms of secreted IgA antibodies indicated that polymers were produced early after immunization, irrespective of the nature of the Ag . When compared with serum antibody and to PBMC cell responses, systemic immunization with polysaccharides induced a minor salivary response dominated by IgG and IgM antibodies . In contrast, the presence of antipolysaccharide antibodies in bile, irrespective of their isotype, paralleled the serum response 14 days after the immunization with polysaccharide Ag . These results suggest that biliary Ig were mostly derived from serum . Different patterns of the expression of MHC class II Ag on T cells, B cells, and monocytes during the course of immunization with protein or polysaccharide Ag were observed: whereas protein Ag induced a high frequency of HLA-DP- and HLA-DR-expressing cells early in the course of immunization, polysaccharide vaccines elicited low and protracted increases of HLA-DP+ T cells . Polysaccharide vaccine covalently coupled to a protein carrier induced a higher frequency of antipolysaccharide antibody-secreting cells in peripheral blood and increased the IgG to IgA ratio among polysaccharide-specific antibody-secreting cells.

Am J Med, 1990 May 14, 88(5A), 20S - 24S
Pulmonary host defenses and oropharyngeal pathogens; Toews GB et al.; The lower respiratory tract is repetitively inoculated with oropharyngeal bacteria and yet pneumonia is an infrequent event . Efficient mechanisms of antibacterial defense are present in the respiratory tract that eliminate microbes before their presence or multiplication leads to disease in the majority of instances . Resident pulmonary defenses consist of aerodynamic defenses, the mucociliary apparatus, alveolar macrophages, complement, and surfactant . These resident defenses can be augmented by the development of an inflammatory response or the development of specific immunity . Significant species variability exists in the efficiency and mechanisms of clearance for oropharyngeal organisms . Streptococci are cleared promptly, Branhamella catarrhalis is cleared slowly, whereas non-typable Haemophilus influenzae multiply before being cleared . A dual phagocytic system of alveolar macrophages and recruited polymorphonuclear leukocytes is required for clearance of most oropharyngeal microbes . Systemic immunization can significantly enhance clearance of non-typable H . influenzae, suggesting immunoprophylaxis might be possible for this organism.

Eur J Clin Microbiol Infect Dis, 1990 May, 9(5), 329 - 36
Disk diffusion susceptibility testing of Haemophilus influenzae using haemophilus test medium; Doern GV et al.; A three-center collaborative study was performed with the aim of determining the reproducibility of disk diffusion and broth microdilution susceptibility tests of Haemophilus influenzae with 19 different antimicrobial agents using a newly described medium, Haemophilus Test Medium . The results of both methods were found to be highly reproducible . Using Haemophilus Test Medium, inhibitory zone diameters and MICs were then determined for 150 test strains of Haemophilus influenzae, selected with an emphasis on known mechanisms of resistance . Regression analysis of zone diameter-MIC comparisons was used to define zone diameter interpretive criteria and MIC correlates for Haemophilus Test Medium disk diffusion tests performed with Haemophilus spp . for the following antimicrobial agents: ampicillin, amoxicillin/clavulanate, ampicillin/sulbactam, cefaclor, cefuroxime, cefamandole, ceftriaxone, cefotaxime, ceftizoxime, ceftazidime, cefixime, trimethoprim/sulfamethoxazole, rifampin, chloramphenicol, tetracycline, imipenem, aztreonam and ciprofloxacin.

Antimicrob Agents Chemother, 1990 May, 34(5), 837 - 43
Pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis; Saez-Llorens X et al.; Pentoxifylline has been shown to decrease endotoxin-induced tumor necrosis factor alpha production and reverse the inflammatory actions of interleukin-1 (IL-1) and tumor necrosis factor on leukocyte function . Because of the potential role of this cytokine-leukocyte interaction in the pathogenesis of bacterial meningitis, we investigated the ability of pentoxifylline to modulate meningeal inflammation in the rabbit meningitis model . Pentoxifylline treatment (initially an intravenous injection of 20 mg/kg followed by 6 mg/kg per h) started 20 min before intracisternal injection of 20 ng of Haemophilus influenzae type b lipooligosaccharide (endotoxin) reduced significantly concentrations in cerebrospinal fluid of leukocytes (P less than 0.0001), protein (P less than 0.001), and lactate (P less than 0.001) during the 9-h infusion compared with values in intravenous-saline-treated rabbits . When pentoxifylline was given 1 h after H . influenzae type b endotoxin, the mean peak lactate and leukocyte concentrations in cerebrospinal fluid were significantly lower than those in control animals . Pentoxifylline also significantly decreased lactate and protein concentrations (P less than 0.05) and tended to diminish leukocyte counts (P = 0.08) compared with results in control animals after antibiotic-induced release of endotoxin in animals with H . influenzae meningitis . In this regard, dexamethasone was superior to pentoxifylline and no synergism was observed when the drugs were combined . Additionally, pentoxifylline attenuated meningeal inflammatory changes induced by intracisternal inoculation of 10 ng of rabbit recombinant IL-1 beta compared with results in either dexamethasone- or saline-treated animals . We conclude that pentoxifylline is effective in this animal model in modulating the meningeal inflammatory response following intracisternal inoculation of H . influenzae type b endotoxin or organisms or rabbit recombinant IL-1beta.

Antimicrob Agents Chemother, 1990 May, 34(5), 733 - 8
Therapeutic studies of cefepime (BMY 28142) in murine meningitis and pharmacokinetics in neonatal rats; Tsai YH et al.; Cefepime (BMY 28142) was compared with ceftazidime, cefotaxime, and moxalactam for efficacy in treating experimental meningitis in mice and neonatal rats . Mice were infected intracranially with Streptococcus pneumoniae, S . agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa and treated intramuscularly . Five- to eight-day-old neonatal rats were injected intracisternally with Haemophilus influenzae, S . pneumoniae, and S . agalactiae and treated intraperitoneally . Cefepime was found to be the most active compound against induced meningitis in mice infected with S . agalactiae . Cefepime was as active as cefotaxime against Staphylococcus aureus meningitis, slightly more active than cefotaxime against S . pneumoniae and E . coli, and as active as ceftazidime against K . pneumoniae and P . aeruginosa meningitis . Cefepime was found to be the most active compound against S . pneumoniae and S . agalactiae meningitis in neonatal rats . Against H . influenzae, cefepime was as active as moxalactam and cefotaxime . Ceftazidime was the least active compound . The pharmacokinetics of cefepime in neonatal rats were similar to those of ceftazidime . Both compounds penetrated well into cerebrospinal fluid and brain tissues of uninfected neonatal rats . Relative concentrations were twice as high as those of cefotaxime and moxalactam.

Clin Exp Immunol, 1990 May, 80(2), 263 - 7
Selective concentration of IgD class-specific antibodies in human milk; Litwin SD et al.; The participation of human IgD class antibody in local immune responses of breast tissue was studied by analysing the sera-to-milk ratios of total IgD, IgM, IgA, IgG isotypes and albumin found in matched samples, and by analysing the sera-to-milk (S/M) ratios of IgD, IgM, IgA, IgG antibodies against Haemophilus influenzae capsular polysaccharide (PRP), phosphorylcholine, tetanus and in some cases diphtheria antigens . The study group consisted of eight women immunized during pregnancy with PRP, and control, unimmunized women . Albumin, and total IgG showed high S/M ratios . IgA had a low S/M ratio as expected, consistent with reports that IgA is locally concentrated . Total IgD and IgM isotype ratio values were intermediate between IgG and IgA suggesting they were selectively concentrated in breast fluids due to local production or transport mechanisms, or both . Ratios for specific antibodies of IgA and IgM isotypes and for total IgA and IgM isotype showed parallel data . Among the IgD antibodies, those specific for PRP and phosphorylcholine suggested a higher degree of selective concentration as compared with tetanus antigen . In the group of unimmunized women, although selective concentration of total IgD was observed, specific antibody studies were inconclusive due to the low milk IgD antibody levels encountered . The results indicate that IgD (and also IgM) may participate in local immune responses of human breast tissues and fluids; possibly influenced by the nature of the antigen, the state of immunization and the hormonal environment (pregnancy).

Arch Dis Child, 1990 May, 65(5), 495 - 8
Changes in bacterial meningitis; Carter PE et al.; In 1964, one of us (WHG) undertook a retrospective study of bacterial meningitis in childhood in the north east of Scotland during the period 1946-61 . We have recently carried out a similar review of cases occurring during 1971-86, to compare the incidence, mortality, and bacteriological patterns . During the earlier period 285 cases occurred, a total incidence of 16.9/100,000 children per year . In the later period 274 children were affected, an annual incidence of 17.8/100,000 . The overall mortality rate fell dramatically from 11.9% to 1.8%, the latter figure comparing favourably with recent published studies from Scandinavia and the United States . There was a change in the bacteriological profile in the second period with a significant rise in cases due to Haemophilus influenzae at all ages . A fall in cases of meningococcal meningitis was significant in infants under 1 year of age only . Possible reasons for the change in the bacteriological pattern are discussed.

Arch Dis Child, 1990 May, 65(5), 491 - 4
Acute epiglottitis in children and adults in Sweden 1981-3; Trollfors B et al.; In a retrospective study of the incidence of acute epiglottitis in Sweden, 485 children and 356 adults fulfilled the following criteria: (a) red and swollen epiglottis visualised at laryngoscopy; (b) stridor or difficulties in swallowing own saliva or water; and (c) temperature greater than or equal to 38 degrees C . The age specific incidence in children (0-14 years) was 10 and in adults (greater than or equal to 15 years) 1.8/100,000/year . These incidence rates were higher than the incidence of Haemophilus influenzae meningitis in the same population . Blood cultures were obtained from 290 children (60%) and 185 adults (52%) . H influenzae was isolated from 267 blood cultures (92%) from children and 98 blood cultures from adults (53%) . Other organisms were isolated from six adults (3%) . An artificial airway was established in 352 children (73%) and in 68 adults (19%); the remainder were treated conservatively . Six children and two adults died . Sweden has a high incidence of acute epiglottitis in children and the disease also occurs in adults . The importance of H influenzae in the aetiology of epiglottitis in all age groups is confirmed, but in adults many cases occur without septicaemia . The mortality is currently very low.

Arch Dis Child, 1990 May, 65(5), 489 - 90
Haemophilus influenzae infections in siblings: the need for prophylaxis; Dale A et al.; An 8 month old child developed Haemophilus influenzae meningitis 12 days after his elder brother had developed epiglottitis . There is not at present in the United Kingdom a recognised policy for prophylactic treatment of contacts of patients with H influenzae infection . Variations in clinical practice were confirmed by the result of a survey of paediatricians in the Northern region.

Pediatr Infect Dis J, 1990 May, 9(5), 333 - 9
Development of serum bactericidal activity following nontypable Haemophilus influenzae acute otitis media; Barenkamp SJ et al.; We monitored the development of serum bactericidal antibody in eight children with acute nontypable Haemophilus influenzae otitis media and correlated its development with the appearance of antibody against lipooligosaccharide and surface-exposed outer membrane proteins of the infecting strains . Complement-dependent bactericidal activity was absent in acute sera but increased to titers of 1:4 to 1:32 in sera obtained 4 to 6 weeks later . Absorption of anti-lipooligosaccharide antibodies from convalescent sera had no effect on bactericidal titers of five patients and resulted in small decreases in titer in three patients . Lipooligosaccharide-absorbed samples had persisting bactericidal titers of 1:4 to 1:16 . Four of eight acute samples lacked antibodies to surface-exposed outer membrane proteins whereas four had low concentrations of antibody directed against one or more Mr 100,000 to 250,000 outer membrane proteins . Convalescent samples from all eight children showed substantial increases in antibodies directed primarily against Mr 100,000 to 250,000 proteins . Thus, both surface-exposed Mr 100,000 to 250,000 outer membrane proteins and lipooligosaccharide are immunogenic during Haemophilus otitis media and are potential targets of bactericidal antibody.

Pediatr Infect Dis J, 1990 May, 9(5), 326 - 32
Outbreak of Haemophilus influenzae type b meningitis in a day care center; Andersson von Rosen I et al.; Three cases of Haemophilus influenzae type b (Hib) meningitis in a Swedish day care center prompted the investigation of the nasopharyngeal carriage in attendees of that day care center (I), and among children in another day center (II) in the same city, but without meningitis cases . Because the evaluation of the spread of Haemophilus influenzae (Hi) isolates through a population, such as children in day care centers, requires stable identification markers for the bacteria, this study used multilocus enzyme electrophoresis to separate Hib carried by day care attendees from the disease-associated Hib clone . The three meningitis episodes were caused by the same clone of Hib (ET14) . This and other Hib clones occurred in the healthy carriers . The frequency of H . influenzae carriage and composition of the H . influenzae flora differed between the two day care centers . Center I with the meningitis cases had a lower overall frequency of H . influenzae carriage, 11 of 40 (28%) compared with both the control day care center (57%) and previous studies . The main difference between the two day care centers was in the nontypable H . influenzae (HiNT) flora . The frequency of HiNT was higher in the center without Hib disease, and there was a higher degree of sharing of HiNT isolates among the children in Center II . This raised the question of an inverse relationship between carriage of HiNT and Hib infection . The results emphasized the importance of accurate identification of the disease isolate in order to estimate the risk of acquisition and dissemination to secondary cases.

Pediatr Infect Dis J, 1990 May, 9(5), 321 - 6
Epidemiology of invasive Haemophilus influenzae type b infections in Bedouins and Jews in southern Israel; Halfon-Yaniv I et al.; We report the epidemiology of invasive Haemophilus influenzae type b disease requiring hospital intervention in Southern Israel, an area that contains two ethnic populations, Bedouins and Jews . The study is based on 107 blood or cerebrospinal fluid culture-positive cases during the years 1984 to 1988 . The annual incidence rate among children younger than 5 years of age was 51/100,000 (48/100,000 for Jews and 58/100,000 for Bedouins) . Thirty-nine percent of patients had meningitis, 32% had pneumonia and 31% had otitis media . Epiglottitis was present in only one case (less than 1%) . The median age was 8 months . Twenty-six percent of the cases were 6 months old or younger, 75% were 1 year old or younger and 87% were 18 months old or younger . Ninety-five percent of all meningitis cases occurred during the first 18 months of life . A projected number of 2938 hospitalization days and 9.8 deaths/year for a population in which 100,000 births occur yearly was calculated . The major impact of invasive H . influenzae type b infections and the very young age involved justify initiation of H . influenzae vaccine studies in our region.

J Clin Microbiol, 1990 May, 28(5), 985 - 8
Antimicrobial susceptibility testing of less commonly isolated Haemophilus species using Haemophilus test medium; Jorgensen JH et al.; Haemophilus test medium (HTM) was developed recently for dilution and disk diffusion antimicrobial agent susceptibility testing of Haemophilus influenzae . The application of HTM to the testing of other, less frequently encountered Haemophilus species recovered from humans was evaluated in this study by using commercially prepared HTM (BBL Microbiology Systems, Cockeysville, Md.) in broth microdilution and agar disk diffusion susceptibility tests with 18 antimicrobial agents . A total of 93.3% of 90 isolates belonging to six Haemophilus species provided acceptable growth in HTM agar disk diffusion tests, while only 63.3% (57 of 90) provided acceptable growth in the broth microdilution tests . However, HTM agar dilution testing provided an alternative method for those strains (primarily H . haemolyticus) which failed to grow adequately in broth . Based on the latest National Committee for Clinical Laboratory Standards guidelines (standard M2-T4) for interpretation of HTM disk tests of H . influenzae, the overall very major, major, and minor errors for all 18 drugs and six species tested were 0.2, 0.7, and 3.4%, respectively . Thus, the use of HTM in agar or broth susceptibility tests can be recommended for testing the less commonly encountered Haemophilus species by using the same test conditions and interpretive guidelines developed for H . influenzae.

Heart Lung, 1990 May, 19(3), 271 - 3
Haemophilus parainfluenzae bacteremia associated with a pacemaker wire localized by gallium scan; Rosenbaum GS et al.; A young woman with a history of sick sinus syndrome and placement of a permanent pacemaker 6 months before admission had fever and Haemophilus parainfluenzae bacteremia . A gallium scan localized the infection to the site of the pacemaker wire . Echocardiograms were negative for any vegetations . The patient responded to cefotaxime and trimethoprim-sulfamethoxazole therapy . We believe that this is the first case of H . parainfluenzae bacteremia associated with a pacemaker wire and localized by gallium scan.

Am Rev Respir Dis, 1990 May, 141(5 Pt 1), 1316 - 21
Haemophilus influenzae infections in patients with chronic obstructive pulmonary disease despite specific antibodies in serum and sputum; Groeneveld K et al.; The titer and specificity of antibodies to the infecting Haemophilus influenzae was determined in sera and sputa from 27 patients with chronic obstructive pulmonary disease (COPD) to analyze the specific immune response . COPD patients had significantly higher serum IgG and IgA antibody titers than 13 healthy controls (mean IgG titers 12,302 and 5,623, respectively; mean IgA titers, 2,398 and 912; p less than 0.001) . The mean IgM titers were comparable: 501 and 447, respectively . Specific IgA antibodies were also detectable in the sputum of the COPD patients (mean IgA antibody titer, 776) . The local antibody production was determined by calculating the relative coefficient of excretion (RCE) to albumin . The mean RCE of 89.1 for IgA indicated statistically significant local production (p less than 0.02), in contrast to a nonsignificant increase for IgG (mean RCE of 3.6) . Specific IgM was below the detection level . Immunoblotting experiments showed that the antibodies in sera from COPD patients and controls were directed against most of the outer membrane proteins of H . influenzae, with individual differences between IgG, IgA, and IgM . The IgA and IgG antibodies in serum had a similar specificity as those in sputum . The appearance or persistence of H . influenzae coincided with minor changes in antibody titer and specificity . From these results we conclude that COPD patients are infected with H . influenzae despite the presence of at least as many antibodies in sputum and serum as in controls and that these antibodies are directed against a variety of antigenic determinants of the infecting strain.

J Allergy Clin Immunol, 1990 May, 85(5), 948 - 53
Response to a Haemophilus influenzae type b diphtheria CRM197 conjugate vaccine in children with a defect of antibody production to Haemophilus influenzae type b polysaccharide; Schneider LC et al.; A defect in antibody response to immunization with Haemophilus influenzae type b (Hib) capsular polysaccharide vaccine has been reported in children with recurrent infections and normal immunoglobin levels . We identified 15 children, aged 2 to 6 years, with this defect, and we evaluated their response to immunization with an Hib capsular oligosaccharide diphtheria CRM197 protein-conjugate vaccine (HbOC) . The children received a series of three vaccines: HbOC at 0 and 8 weeks, and the Hib polysaccharide vaccine at 16 weeks . Levels of antibody to the Hib capsular polysaccharide (polyribosyl ribitol phosphate, PRP) and to diphtheria toxoid were obtained before and 4 weeks after each vaccination . The geometric mean serum anti-PRP concentration was 0.17 microgram/ml before immunization and 29.3 micrograms/ml after the second HbOC immunization (week 12) . All 15 children had postvaccination anti-PRP antibody levels greater than 1.0 microgram/ml after receiving the second HbOC (week 12) . In addition, booster responses were observed after the second Hib conjugate in 13 of the patients and after the Hib polysaccharide in four of the patients . All patients with low preimmunization diphtheria titers had a response to the diphtheria toxoid . These results suggest that conjugation of Hib polysaccharide with diphtheria CRM197 overcomes the defective antibody response to Hib oligosaccharide in children who are initially observed with recurrent infections and inability to respond to the Hib polysaccharide vaccine.

J Infect Dis, 1990 May, 161(5), 926 - 31
Risk of Haemophilus influenzae type b disease in children with cancer and response of immunocompromised leukemic children to a conjugate vaccine; Feldman S et al.; From 1969 to 1988, 8 cases of systemic Haemophilus influenzae type b (Hib) disease occurred among 5288 patients with cancer . For the first 4 years of life, systemic Hib disease was significantly greater in leukemic children than in the general population (606/100,000 vs . 90/100,000, respectively) . Fifty children aged 2-6 years with acute leukemia were vaccinated with a Hib conjugate vaccine, ProHibit . The overall response rate was 50%; however, 75% of children receiving leukemic therapy for less than 12 months responded versus 18% of those treated longer . After vaccination, the geometric mean antibody concentration was 7.2 micrograms/ml, appreciably lower than for normal children of similar ages . After 12 months, the geometric mean antibody concentration had declined to 0.35 micrograms/ml, and 75% of subjects had antibody levels greater than or equal to 0.15 micrograms/ml . A booster dose for unsuccessfully vaccinated subjects was of minimal benefit . Children with acute leukemia in remission who were treated according to the leukemia therapy protocol of St . Jude Children's Research Hospital had a good likelihood of responding to the conjugate Hib vaccine if administered within a year of initiation of chemotherapy.

Microb Pathog, 1990 May, 8(5), 315 - 23
Anti-adhesive activity of human casein against Streptococcus pneumoniae and Haemophilus influenzae; Aniansson G et al.; The casein fraction of human milk was found to inhibit the attachment of Streptococcus pneumoniae and Haemophilus influenzae human respiratory tract epithelial cells . The inhibitory activity for S . pneumoniae remained after heat and trypsin treatment of the casein and was found in oligosaccharides released from casein . kappa-Casein, which is the most highly glycosylated casein component, inhibited pneumococcal attachment at concentrations similar to the whole casein fraction . The results are consistent with the known recognition of GlcNAc beta 1-3Gal by S . pneumoniae, since human milk and bovine colostrum, which contain GlcNAc, inhibited attachment, but mature bovine milk lacking GlcNAc did not . The effect on H . influenzae was similar to that on S . pneumoniae in that the attachment was inhibited by human casein and bovine colostrum, but not by either mature bovine milk or by the bovine casein fraction . The kappa-casein component of human milk was a less efficient inhibitor of H . influenzae attachment than the whole casein fraction and the free oligosaccharides were inactive . This anti-microbial effect of human casein represents a new mechanism for the protection by breast-milk against respiratory tract infection.

Monatsschr Kinderheilkd, 1990 May, 138(5), 240 - 3
{Haemophilus influenzae type B . Disease and prevention}; Stehr K; Haemophilus influenzae is a gram-negative rod, causing severe infections in childhood, including meningitis, sepsis, epiglottits, pneumonia and otitis . Most of the invasive infections are due to serotype b . Since ampicillin-resistance is increasing, modern cephalosporines like cefotaxime and ceftriaxone are the antibiotics of choice in severe disease . Bacterial meningitis due to Haemophilus influenzae and epiglottitis are both still life-threatening diseases with a lethality of 5% to 25%, and there are severe sequelae in 35% of meningitis cases . Efforts have been made to develop efficacious vaccines . While immunogenicity of type b polysaccharide was low in the high-risk age (below 18 months), conjugated vaccines with either diphtheria-toxoid or Neisseria meningitis outer membrane protein and the Hib polysaccharide were found to be strongly immunogenic even in the first months of life . These vaccines show every few side-effects and can easily be combined with other immunizations such as DPT and DT . Thus, the incidence of invasive infections due to Haemophilus influenzae type b might decline in future.

Pathol Biol (Paris), 1990 May, 38(5), 407 - 12
{In vitro antibacterial activity of rokitamycin, a new macrolide antibiotic . Results of a multicenter study}; Soussy CJ et al.; Minimal inhibitory concentrations (MIC) of rokitamycin (R) were evaluated by agar dilution for 914 bacterial strain isolated in 4 hospitals and classed as a function of susceptibility and resistance to Macrolides-Lincosamides-Streptogramines group (MLS) . MICs of R ranged from 0.06 to 1 microgram/ml (mode MIC 0.25-0.5) on Staphylococci susceptible to MLS and on MLSB inducible strains; R was inactive on MLSB constitutive strains . MICs of R ranged from 0.008 to 0.5 microgram/ml (mode MIC 0.06 to 0.25) for Streptococci and Pneumococci susceptible to erythromycin (E) and from 0.06 to greater than 128 for strains resistant to E . Enterococci susceptible to E were inhibited by 0.06 to 0.5 microgram/ml (mode MIC 0.5) and strains resistant to E by 0.25 to greater than 128 . Haemophilus were inhibited by 0.5 to 0.65 microgram/ml (mode MICs of R ranged generally from 0.016 to 0.5 microgram/ml (mode MIC 0.12) for C . perfringens and from 0.016 to 1 (mode MIC 0.06) for B . fragilis . Thus, R was shown to be among macrolide antibiotics of resistance strains . Its activity was superior to that of other products of this group spiramycin, josamycin, miokamycin, particularly on Gram positive cocci . R had a good activity on Neisseria, Branhamella, anaerobes and, as others macrolides, was poorly active on Haemophilus.

Rev Infect Dis, 1990 May-Jun, 12 Suppl 4, S483 - 9; discussion S489-91
Polyvalent group B streptococcal immune globulin for intravenous administration: overview; Fischer GW et al.; Immunoglobulin therapy is becoming an important modality for the prevention and treatment of bacterial and viral infection . Standard intravenous immunoglobulin (IVIG) is made from large pools of plasma obtained from normal blood donors . However, lot-to-lot variation in titers of antibody to specific microbial pathogens may diminish therapeutic efficacy . Since group B Streptococcus (GBS) is an important neonatal pathogen, a preparation with high titers of activity against GBS was prepared and studied . Plasma was obtained from volunteers immunized with a polyvalent GBS vaccine and was processed by the Swiss Red Cross for intravenous infusion . This high-titered GBS intravenous immunoglobulin (GBS-IVIG) was shown to be superior both in vitro and in vivo to standard IVIG . GBS-IVIG provided protection when therapy was delayed for up to 24 hours after infection . Standard IVIG did not protect animals against all GBS strains . However, GBS-IVIG enhanced survival from infection with all strains tested, even when the challenge dose of GBS was increased by 2 log units . Specific hyperimmune globulins to pathogens such as Haemophilus influenzae and Streptococcus pneumoniae have also been studied . Immunization of adult volunteers as a means of obtaining hyperimmune globulin appears to be an effective method of producing high-titered pathogen-specific preparations of IVIG.

J Clin Microbiol, 1990 May, 28(5), 833 - 6
Major subtypes of invasive Haemophilus influenzae from 1983 to 1985 in Atlanta, Ga; Elliott JA et al.; We compared outer membrane protein (OMP) patterns of Haemophilus influenzae isolated in metropolitan Atlanta, Ga., from July 1983 to June 1985 . Of 74 randomly selected H . influenzae serotype b, biotype I, isolates (24% of the total number of H . influenzae, and 32% of the total number of H . influenzae serotype b, biotype I, isolates), 66 (89.2%) had the same OMP pattern . Of the remaining eight, five (6.7%) had an identical OMP pattern . The other three isolates had separate and distinct patterns . A greater diversity of OMP patterns was found with H . influenzae serotype b, biotype II, and nonserotypeable H . influenzae . Of the 18 H . influenzae serotype b, biotype II, isolates (5.8% of the total number of H . influenzae isolates), 1 had an OMP pattern similar to that of the predominate biotype I OMP type, 6 (33% of the biotype II) had the same pattern, and 11 had heterogeneous patterns . Of the 19 recoverable, nonserotypeable biotype II isolates (6.8% of the total number of H . influenzae), 18 had different OMP patterns, and no pattern was similar to those observed with serotype b . These findings indicate that most H . influenzae strains isolated during this 2-year period were indistinguishable by serotype, biotype, or OMP patterns.

Pediatrics, 1990 May, 85(5), 722 - 6
Microbiology of empyema in children and adolescents; Brook I; The microbiology of empyema was studied in 72 children and adolescents whose specimens yielded bacterial growth after inoculation for aerobic and anaerobic bacteria . A total of 93 organisms, 60 aerobic or facultative and 33 anaerobic, were isolated . Aerobic bacteria was isolated in 48 (67%) patients, anaerobic bacteria in 17 (24%), and mixed aerobic and anaerobic bacteria in 7 (10%) . The predominant aerobic or facultative bacteria were Haemophilus influenzae (15 isolates), Streptococcus pneumoniae (13), and Staphylococcus aureus (10) . The predominant anaerobes were Bacteroides sp (15 isolates, including 7 Bacteroides fragilis group and 5 Bacteroides melaninogenicus group), anaerobic cocci (9), and Fusobacterium sp (6) . beta-lactamase activity was detected in at least one isolate in 20 (37%) of the 54 tested patients . These included all 8 tested S aureus and 7 B fragilis group, 3 of 10 H influenzae, 2 of 4 B melaninogenicus group, and 1 of 2 Klebsiella pneumoniae . Most cases of S pneumoniae and H influenzae were associated with pneumonia . The recovery of anaerobic bacteria was mostly associated with the concomitant diagnosis of aspiration pneumonia, lung abscess, subdiaphragmatic abscess, and abscesses of dental or oropharyngeal origin . The data highlight the importance of anaerobic bacteria in selected cases of empyema in children and adolescents.

Clin Ther, 1990 May-Jun, 12(3), 200 - 5
Treatment of chancroid with spectinomycin or co-trimoxazole; Traisupa A et al.; Chancroid, the third most prevalent venereal disease in Thailand, was treated with a single 2-gm dose of spectinomycin, or two tablets of co-trimoxazole (trimethoprim-sulfamethoxazole) twice daily for seven days . The differences in cure rates between the two groups were statistically significant . The chancroidal ulcers were cured in 93.7% of 175 patients treated with spectinomycin, and in 48.2% of 168 co-trimoxazole-treated patients (P less than 0.01) . The in vitro susceptibility of Haemophilus ducreyi to spectinomycin was 4 to 16 micrograms/ml and to co-trimoxazole 32 micrograms/ml or higher . Thus we found that a single-dose regimen of spectinomycin was significantly more effective than the standard seven-day regimen of co-trimoxazole for the treatment of chancroid.

J Gen Microbiol, 1990 May, 136 ( Pt 5), 927 - 33
Siderophore-independent acquisition of transferrin-bound iron by Haemophilus influenzae type b; Morton DJ et al.; The specificity by which Haemophilus species acquired iron from transferrin (TF) was investigated . In a plate bioassay H . influenzae used iron bound to human, bovine and rabbit TFs but not mouse, rat, dog, horse, guinea-pig, pig or ovo- TFs or human and bovine lactoferrins . In contrast, H . pleuropneumoniae used iron only from pig TF whilst H . parainfluenzae was unable to utilize iron bound to any of the human or animal TFs tested . The inhibition of growth imposed on H . influenzae type b strain Eagan by the addition of the synthetic iron chelator EDDA to the culture medium was reversed by 30% iron-saturated human TF added directly to the medium but not when the TF was contained inside a dialysis bag . Dot-blotting of whole cells revealed that human TF bound to the surface of bacteria cultured in iron-restricted but not in iron-plentiful media . Incubation of whole bacterial cells in the presence of the proteolytic enzyme trypsin also abolished TF-binding activity, suggesting that the TF receptor was a protein . In competition dot blotting experiments, human and bovine but not rabbit, dog, mouse or guinea-pig TFs blocked the binding of a horseradish peroxidase--human TF conjugate . SDS-PAGE and Western blotting of outer membranes revealed the presence of a TF-binding protein of approximately 72 kDa . These results suggest that the acquisition of TF-bound iron by H . influenzae type b probably involves a direct interaction with an outer-membrane protein which shows some TF-species specificity.

Eur J Clin Microbiol Infect Dis, 1990 May, 9(5), 361 - 5
In vitro activity of tosufloxacin (A-60969) and clarithromycin (A-56268, TE-031) against resistant Haemophilus influenzae, Streptococcus pneumoniae and Branhamella catarrhalis isolates; Bryan JP et al.; The activity of tosufloxacin (A-60969), a new oral quinolone, and clarithromycin (A-56268, TE-031), a new oral macrolide, was compared in vitro to that of other oral quinolones and beta-lactam antimicrobial agents against clinical isolates of ampicillin and/or chloramphenicol resistant Haemophilus influenzae, penicillin resistant Streptococcus pneumoniae and beta-lactamase producing Branhamella catarrhalis . Results were compared to those for sensitive isolates . Tosufloxacin was the most active compound against Haemophilus influenzae and was more active than ciprofloxacin or ofloxacin against all strains of Streptococcus pneumoniae . Tosufloxacin was also more active than any of the beta-lactam drugs tested against penicillin resistant or relatively penicillin resistant isolates . Clarithromycin was the most active compound tested against both penicillin sensitive and penicillin resistant Streptococcus pneumoniae, and was as active as ciprofloxacin against Branhamella catarrhalis . In view of the favourable in vitro activity against common bacterial respiratory pathogens, tosufloxacin should be considered for clinical trials in adults with respiratory tract infections, while clarithromycin might be useful in treatment of infection with these organisms in all age groups.

J Int Med Res, 1990 May-Jun, 18(3), 235 - 9
Comparative study of cefuroxime axetil suspension and amoxycillin syrup in the treatment of acute otitis media in general practice; Brodie DP et al.; In a multicentre general practice study, 660 children aged between 3 months and 12 years with otitis media were randomized to receive a 10-day course of cefuroxime axetil suspension or amoxycillin syrup . Children under 2 years of age were given 125 mg cefuroxime axetil twice daily after food or 125 mg amoxycillin three times daily; older children received 250 mg cefuroxime axetil twice daily or 250 mg amoxycillin three times daily . The overall cure or improvement rate was 94.3% for those treated with cefuroxime axetil and 94.5% for those receiving amoxycillin . Both treatments were well tolerated, with no differences in the number of patients who experienced at least one adverse event or who were withdrawn from treatment . Haemophilus influenzae was isolated in 29% of specimens obtained, Streptococcus pneumoniae in 22% and Moraxella catarrhalis in 6% . Some Strep . pneumonia and M . catarrhalis infections were resistant to amoxycillin . It is concluded that cefuroxime axetil suspension given twice daily has comparable efficacy to amoxycillin syrup given three times daily in the treatment of children with otitis media.

Am J Vet Res, 1990 May, 51(5), 759 - 62
Influence of recombinant bovine interferon gamma and dexamethasone on pneumonia attributable to Haemophilus somnus in calves; Chiang YW et al.; The influence of recombinant bovine interferon gamma (rBoIFN-gamma) treatment on resistance of clinically normal and dexamethasone-treated calves to Haemophilus somnus infection was evaluated . Four groups of 6 calves each were treated with saline solution (controls), dexamethasone (0.04 mg/kg of body weight/for 3 days), rBoIFN-gamma (2 micrograms/kg for 2 days), or dexamethasone and rBoIFN-gamma (aforementioned dosages) . All treatments were started 24 hours before intrabronchial challenge exposure with 5 x 10(9) colony-forming units of H somnus . Rectal temperature and WBC count were monitored daily . Two of the dexamethasone-treated calves died of pneumonia 4 days after challenge exposure and were necropsied . All other calves were euthanatized and necropsied 7 days after challenge exposure . All calves had pneumonia of variable intensity . Dexamethasone-treated calves had increased volume of pneumonic lung (P less than 0.05) and increased severity of pneumonia, compared with control calves . Recombinant bovine interferon gamma treatment resulted in reduction in pneumonic lung volume and severity of pneumonia in dexamethasone-treated calves (P less than 0.05), although it did not influence severity of pneumonia in nondexamethasone-treated calves.

J Infect Dis, 1990 May, 161(5), 922 - 5
Kappa and lambda light chain composition of antibody to the capsular polysaccharide of Haemophilus influenzae type b; Ambrosino DM et al.; Concentrations of total immunoglobulins bearing kappa and lambda light chains were measured in the sera of 215 healthy white children aged 6 months to 10 years . Both kappa and lambda concentrations increased with age . However, the concentration of immunoglobulins bearing kappa light chains increased at a greater rate than those bearing lambda light chains (P = .01) . Thus, the kappa:lambda ratio of the youngest children (6-24 months) was significantly lower than that of the oldest (25-130 months) (P = .0015) . The relationship between the IgG antibody concentration and the light chain composition of the specific antibody directed to Haemophilus influenzae type b (Hib) polysaccharide was also assessed in 62 of 215 serum samples with detectable Hib antibody . The IgG Hib antibody concentration was strongly correlated with the kappa:lambda Hib antibody ratio (r = .60, P = .001), and this correlation was independent of age . Thus, light chain selection and response to polysaccharides may be regulated by common mechanisms that mature late in ontogeny.

Med J Aust, 1990 Apr 16, 152(8), 413 - 6
Protection against recurrent acute bronchitis after oral immunization with killed Haemophilus influenzae; Clancy RL et al.; Subjects prone to recurrent acute bronchitis were admitted to a six-month double-blind clinical study, in which the value of oral immunization with a preparation of killed Haemophilus influenzae was tested . Most subjects had early smoking-related chronic lung disease, unrecognized by either the patient or his/her doctor . Subjects taking the active agent had a 41% reduction in the total number of episodes of acute bronchitis (P = 0.16), a 60% reduction in the number of episodes of acute wheezy bronchitis (P = 0.02) and a 58% reduction in antibiotic use (P = 0.07) . The power of analysis was restricted by the small study group . Parameters of episode severity favoured the test group, suggesting that individual episodes of acute bronchitis in subjects taking an oral preparation of killed H . influenzae were less severe than in those taking placebo tablets . Oral immunization with H . influenzae selectively reduced the increase in colonization of the oropharynx with H . influenzae which occurred in the group taking placebo . This is the first demonstration that the common mucosal system can be activated to modify a colonization pattern at a distant site.

Infect Immun, 1990 Apr, 58(4), 903 - 8
Cloning and expression in Escherichia coli of LKP pilus genes from a nontypeable Haemophilus influenzae strain; Kar S et al.; Nontypeable Haemophilus influenzae HF0295, isolated by aspiration from the middle ear of a patient with otitis media, expresses long, thick, and hemagglutinating pili of a single serotype (LKP1) on its surface . An intact pilus vaccine consisting of the LKP1 serotype protected chinchillas against experimental otitis media (C . C . Brinton, Jr., M . J . Carter, D . B . Derber, S . Kar, J . A . Kramarik, A . C . C . To, S . C . M . To, and S . W . Wood, Pediatr . Infect . Dis . J . 8:554-561, 1989; R . B . Karasic, D . J . Beste, S . C . M . To, W . J . Doyle, S . W . Wood, M . J . Carter, A . C . C . To, K . Tanpowpong, C . D . Bluestone, and C . C . Brinton, Jr., Pediatr . Infect . Dis . J . 8:562-565, 1989) . The genes encoding LKP1 pili were cloned from a genomic library of the clinical strain as a 12.5-kilobase insert on a plasmid vector and inserted into Escherichia coli K-12 . Transposon mutagenesis and deletion constructs mapped the pilus-coding region within a 7-kilobase region of insert DNA . The recombinant bacteria were found by electron microscopy to express pili morphologically similar to LKP1 pili . Purified pilus rods from the recombinant and its parental strain were composed of a single detectable protein with an apparent molecular weight of 27,500 . Antibodies raised against LKP1 pili purified from H . influenzae immunologically reacted with pili from the recombinant bacteria . Pili from both strains also adhered to human erythrocytes and buccal cells with the same specificity.

Avian Dis, 1990 Apr-Jun, 34(2), 364 - 8
Serological classification of Japanese isolates of Haemophilus paragallinarum using two serovar-specific monoclonal antibodies; Yamaguchi T et al.; A serological classification of 106 Japanese isolates of Haemophilus paragalinarum recovered from 1960 to 1984 was performed by dot-blotting and hemagglutination-inhibition (HI) tests using two serovar-specific monoclonal antibodies (MAbs), E5C12D10 and F2E6 . By the dot-blotting test, 49 of the isolates were serovar A and 55 isolates were serovar C, and the two remaining isolates did not react with either MAb . These two nontypable strains had no hemagglutinating activity against chicken erythrocytes and were nonpathogenic to chickens . Although 49 serovar A isolates were serotyped by the HI test, only 23 of the 55 serovar C isolates could be serotyped . The remaining 32 isolates could not be serotyped because no or low hemagglutinating activity could be detected . Our results indicate that H . paragallinarum serovars A and C have both been present in Japan since 1960, with serovar A isolates being dominant before 1970 and serovar C isolates more prevalent than serovar A since 1970.

Can J Vet Res, 1990 Apr, 54(2), 244 - 50
Analysis of southern Ontario Actinobacillus (Haemophilus) pleuropneumoniae isolates by restriction endonuclease fingerprinting; MacInnes JI et al.; Isolates of Actinobacillus (Haemophilus) pleuropheumoniae were studied by restriction endonuclease fingerprinting (REF) analysis using the enzymes BamHI and HindIII . Restriction fragments were resolved by polyacrylamide gel electrophoresis and visualized by silver staining . Except for serotypes 1 and 9, reference strains of A . pleuropneumoniae serotypes 1 to 10 had clearly distinguishable REF profiles . Analysis of REF profiles of southern Ontario field isolates revealed limited heterogeneity amongst isolates of serotype 1 or serotype 5 . The REF profiles of the serotype 7 isolates studied showed greater variation . Heterogeneity could not be correlated with the presence of plasmids nor with antibiotic resistance . Limited heterogeneity could also be detected amongst REF profiles of A . pleuropneumoniae isolates recovered from a closed herd suggesting that there is a small amount of genetic variation within clonal populations.

Thorax, 1990 Apr, 45(4), 254 - 8
A hospital study of community acquired pneumonia in the elderly; Venkatesan P et al.; Studies on community acquired pneumonia in the United States in patients over the age of 65 years have shown that Gram negative bacilli account for an appreciable proportion of cases, in addition to usual pathogens such as Streptococcus pneumoniae and Haemophilus influenzae . There have been no reports of community acquired pneumonia in the elderly in the United Kingdom . We undertook such a study to determine the clinical features, aetiology, and outcome . Seventy three patients (38 men) with ages ranging from 65 to 97 (median 79) years were studied prospectively . Pneumonia was defined as an acute lower respiratory tract infection with new, previously unrecorded shadowing on a chest radiograph . Patients with severe chronic illness in whom pneumonia was an expected terminal event were excluded . Nearly all the patients (96%) had respiratory symptoms or signs but many had features that might obscure the true diagnosis of pneumonia . Over half the patients had non-respiratory symptoms and over a third had no systemic signs of infection . A pathogen was identified in 43% of patients, most commonly Streptococcus pneumoniae, Haemophilus influenzae and influenza B virus . Gram negative bacilli were not seen . The mortality rate was high (33%) . Early deaths were due to infection whereas later deaths were associated with other factors, such as stroke (two patients) and pulmonary embolism (two patients) . Prognostic indicators for mortality were apyrexia, systolic hypotension, increasing hypoxaemia, and new urinary incontinence . As the range of pathogens causing pneumonia was the same in the elderly in this study as in other age groups it is suggested that initial antibiotic treatment for patients in this age group should always cover S pneumoniae and H influenzae.

J Antimicrob Chemother, 1990 Apr, 25(4), 525 - 34
Penicillin-binding proteins and ampicillin resistance in Haemophilus influenzae; Mendelman PM et al.; Ampicillin-resistant, non-beta-lactamase-producing isolates of Haemophilus influenzae contain a variety of penicillin-binding protein (PBP) patterns that differ from the single pattern of eight PBPs characteristic of susceptible strains . During genetic transformation of resistance, only some of the anomalies in PBP pattern were transformed, specifically those relating to the penicillin-binding capacities of PBPs 4 (Mr of 62,000) and 5 (Mr of 59,000) and, in some transformations, PBP 3 (Mr of 71,000) . Comparison of the binding of penicillin by PBPs 4 and 5 of three resistant transformants (derived with DNA from different donors) revealed a decrease in the rate of PBP acylation and no appreciable change in the rate of deacylation as compared to the susceptible recipient . Thus, rapid turnover of these PBPs does not play a role . Retransformation studies confirm that altered PBPs 3, 4, and 5 are associated with resistance and suggest that these PBPs are major targets for the beta-lactam antibiotics in H . influenzae.

Acta Paediatr Scand, 1990 Apr, 79(4), 454 - 60
Decreased absence due to infectious diseases in children at two day care centres over an eight-year interval; Soderstrom M et al.; Causes of absence were recorded at two day care centres during a seven-month period in 1979/80 and a corresponding period in 1987/88, for 82 and 87 children, respectively . During the eight-year interval absence due to disease decreased from 8.2% to 5.7% of total day-care days . A decrease in epidemic diseases during the eight years was evident . There were no cases of morbilli, parotitis or rubella in 1987/88, following an immunisation programme for these diseases initiated in 1982 . An out-break of varicellae occurred in 1979/80, as compared with only few cases in 1987/88 . Respiratory tract infection was the most common type of illness both in 1979/80 and in 1987/88 . The mean number of illness episodes of respiratory tract infections per child, aged 5-6, was significantly higher in the earlier than in the later period, whereas no corresponding difference was evident for the younger age groups . Although, in the meantime parent benefits for home care of sick children had become more generous, attendance at the two day care centres rose from 62% in 1979/80 to 79% in 1987/88 of total day-care days, suggesting a truly decreased morbidity . The carriage rates of pneumococci, Haemophilus influenzae and Branhamella catarrhalis decreased with increasing age of the children, and that of beta-haemolytic streptococci increased; however, the carriage rates during the two periods did not differ significantly . The overall isolation frequencies of these bacteria were 72%, 43% and 38%, respectively, for children aged 1-2, 3-4, and 5-6 years, and 5.9% for the staff.

J Antimicrob Chemother, 1990 Apr, 25 Suppl C, 115 - 25
Septicaemia in Hong Kong; French GL et al.; In a five-year prospective study of blood culture-positive septicaemia in a Hong Kong teaching hospital there were 2211 clinically-significant episodes, of which 16% occurred in children less than 15 years old . The microbiology and clinical features were broadly similar to those seen in Europe and North America, but with some important differences . Two-thirds of episodes were community-acquired . The most common organism isolated from community-acquired septicaemias was Escherichia coli and the source, most commonly, the urinary tract . However, the biliary tract was the second most common source of community-acquired infection (25%), reflecting the frequency of liver disease in Hong Kong . Three per cent of community-acquired septicaemias were associated with endocarditis; half of these were with viridans streptococci, usually in patients with rheumatic heart disease, and 40% were in drug addicts with methicillin-sensitive Staphylococcus aureus . The commonest organisms causing community-acquired childhood infections were Salmonella spp . (27%) and Streptococcus pneumoniae (22%), whereas pneumococci accounted for only 3% of adult community-acquired micro-organisms . Haemophilus influenzae infections were uncommon and there was no case of meningococcal or gonococcal septicaemia . The commonest cause of hospital-acquired septicaemia was Staph . aureus (24%), of which 46% were methicillin-resistant . The characteristics of septicaemia in Hong Kong are influenced by the patient population structure, endemic disease patterns, local medical practice and socio-economic factors, but the rarity of Str . pneumoniae in adults and of H . influenzae and Neisseria meningitidis in children is unexplained.

Pediatr Res, 1990 Apr, 27(4 Pt 1), 358 - 64
Variability in the functional activity of vaccine-induced antibody to Haemophilus influenzae type b; Amir J et al.; Sera from 3 of 30 adults vaccinated with Haemophilus influenzae type b polysaccharide vaccine (Hib PS) had poor complement-mediated bacterial activity despite the presence of anti-Hib PS antibody concentrations of 8.6 to 20.5 micrograms/mL . These "nonkiller" antibodies killed less than 0.4 log cfu/mL compared to greater than 3 logs with all but one of the other sera . To investigate the basis of this poor functional activity, we characterized in detail the IgG antibodies to Hib PS present in two of the nonkiller sera, and compared the results with two of the "killer" sera . The latter were selected based on comparable levels of total antibody to Hib PS . No consistent differences were found between the relative proportions of IgG or IgA antibody to total anti-Hib PS antibody, or the respective ratios of IgG1 to IgG2 antibody in the nonkiller and killer sera . IgG fractions, and IgG affinity purified antibody to Hib PS were prepared . When tested at 2 micrograms/mL of antibody, the IgG fractions from the two nonkiller sera had much lower bactericidal activity than the corresponding fractions from the killer sera (3 logs less killing), and the former also had lower complement-mediated opsonic activity (20 and 13% uptake by human PMN compared to 62 and 93%) . These data show the striking variability in the functional activity of vaccine-induced antibody to Hib PS . Antibody functional activity is likely to be affected by a number of factors but one important variable appears to be avidity since the IgG anti-Hib PS antibody from the two nonkiller sera had 2- to 5-fold lower avidity than the IgG antibody from the two killer sera.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatr Infect Dis J, 1990 Apr, 9(4), 252 - 7
Haemophilus influenzae type b infections in Victoria, Australia, 1985 to 1987; Gilbert GL et al.; Invasive Haemophilus influenzae type b (HIB) infections occurring from 1985 to 1987 in children younger than 16 years of age living in the state of Victoria were reviewed . There were 547 cases which fulfilled the case definition, including 231 cases of meningitis, 219 of epiglottitis and 97 other infections; 14 (2.6%) children died, 8 with meningitis, 5 with epiglottitis and 1 with pneumonia . Ninety-five percent of cases occurred in children younger than 5 years of age, in whom the case attack rate was 58.5/100,000/annum . Nearly two-thirds of cases (46% of meningitis; 91% of epiglottitis; 45% of other infections) occurred in children more than 18 months of age (the age at which vaccine is presently given in the United States) . Compared with the United States, the case attack rate for HIB disease in Victoria is lower, the mean age of affected children higher and the proportion with epiglottitis is greater . However, the incidence, age distribution and clinical manifestations of HIB disease in Victoria are similar to those described in Scandinavia before the successful introduction of vaccines . Effective conjugate vaccines against HIB disease are now available and the majority of cases are preventable (depending on the immunization schedule used) . These data suggest that immunization of Victorian children against HIB infection should be cost-effective.

Pediatr Infect Dis J, 1990 Apr, 9(4), 241 - 5
Mycoplasmal infections of cerebrospinal fluid in newborn infants from a community hospital population; Waites KB et al.; Mycoplasma hominis or Ureaplasma urealyticum have previously been isolated from cerebrospinal fluid (CSF) in 13 of 100 newborn infants tested from a high risk university hospital population where the mothers were of predominantly lower income and socioeconomic status and had often received little or no prenatal care . We sought to determine whether such infections occur in neonates born to women cared for mainly through private obstetric practices and who delivered in 4 suburban community hospitals . CSF cultures were done in 318 infants during an 8-month period . M . hominis was isolated from 9 and U . urealyticum from 5 CSF cultures . Four infants infected with U . urealyticum and 3 infected with M . hominis were born at term . One infant infected with U . urealyticum had a birth weight of less than 1000 g . In 5 infants clearance of the infecting organism was documented without specific treatment . Twelve infants had good perinatal outcomes regardless of treatment and 2 died . One death in a 2240-g infant infected with M . hominis was associated with Haemophilus influenzae sepsis and pneumonia . The other death occurred 3 days after birth in a 630-g infant infected with U . urealyticum who had evidence of meningitis and intraventricular hemorrhage . Results of this study suggest that mycoplasmas are common causes of neonatal CSF infections, not only in high risk populations, but also in the general population.

J Natl Med Assoc, 1990 Apr, 82(4), 265 - 70
Length of hospital stay in veteran surgical service patients with nosocomial infections; Flournoy DJ et al.; Four hundred ninety-nine nosocomial infections (with 657 isolates) in 288 Surgical Service patients were monitored from February 1986 to June 1987 (17 months) to determine the influence that pathogen or site of infection had on the length of hospital stay . Patients with upper respiratory and skin infections were more likely to have significantly longer length of stay than those with infections in other sites . Infections with Haemophilus influenzae and Pseudomonas aeruginosa were more likely to yield longer culture to discharge periods than other organisms in certain settings . Extended lengths of stay were common in patients with nosocomial infections.

J Exp Pathol (Oxford), 1990 Apr, 71(2), 233 - 44
Characterization of skin lesions in mice following intradermal inoculation of Haemophilus ducreyi; Tuffrey M et al.; Twelve strains of H . ducreyi, which included two reference strains, were each inoculated intradermally into the flanks of CBA mice . All strains produced self-limited lesions which were macroscopically and microscopically typical of those seen in chancroid . Pustular nodules, about 5mm in diameter, developed at all inoculation sites by the second day when 10(7) organisms were inoculated . Approximately half of these lesions ulcerated and all had regressed by 2 weeks . Smaller nodules developed at about half the sites from the second to the fifth day when 10(6) or 10(5) organisms were given, but these did not ulcerate . No lesions were seen when 10(3) organisms were inoculated . Organisms were recovered from the lesions up to 11 days after inoculation . Specific H . ducreyi antigen, sought by a monoclonal antibody test, was detected in lesions up to 15 days following inoculation . Heat-killed organisms of H . ducreyi also produced nodules and ulcers although these were slightly smaller than those which developed after inoculation of viable bacteria . Similar lesions to those caused by H . ducreyi were produced after intradermal inoculation of about 10(8) viable or killed Neisseria gonorrhoeae organisms . Treatment of mice with ceftriaxone had little or no effect on the subsequent development of H . ducreyi-induced lesions . These findings indicated that the lesions were not produced specifically by viable H . ducreyi organisms . Ulcers were also produced following intradermal inoculation of purified lipopolysaccharide (LPS) from H . ducreyi or N . gonorrhoeae, but not by cell-free filtrates prepared from H . ducreyi cultures indicating a possible role for LPS in the pathogenesis of ulcerative skin lesions.

Can Assoc Radiol J, 1990 Apr, 41(2), 98 - 9
Haemophilus influenzae abscess presenting as an asymptomatic lung mass; Balter MS et al.; We report the radiographic and computed tomographic findings in an asymptomatic patient who had a Haemophilus influenzae lung abscess . The diagnosis was made by Gram's staining and culture of abscess material obtained by transthoracic needle aspiration . The radiographic abnormalities cleared after specific antimicrobial therapy.

Am J Dis Child, 1990 Apr, 144(4), 463 - 5
Bacterial meningitis in older children; Bonadio WA et al.; A review was performed of 25 cases of bacterial meningitis in previously healthy children aged 6 years or older during a 10-year period . The rate of infection in this age group relative to all cases of pediatric bacterial meningitis was 4% . Pathogens included Haemophilus influenzae type b in 10 cases (40%), Neisseria meningitidis in 9 cases (36%), and Streptococcus pneumoniae in 6 cases (24%) . Physical findings revealed 21 patients (84%) with some degree of altered consciousness and 25 patients (100%) with nuchal rigidity . In all instances, the cerebrospinal fluid exhibited pleocytosis with a predominance of polymorphonuclear leukocytes . Eleven patients (44%) were afebrile on presentation . Of 22 surviving patients, 10 (45%) were afebrile without subsequent fever after administration of the initial dose of antibiotics, in 5 (23%) fever resolved within 24 hours, and in 6 (27%) fever resolved within 48 hours of treatment; there was no instance of prolonged or secondary fever noted . Death occurred in 3 cases (12%) . Bacterial meningitis is uncommon in older children . As compared with younger children, older children with bacterial meningitis commonly present without fever and tend to have their fever resolve shortly after effective antibiotic therapy is initiated without manifesting prolonged or secondary fever patterns . Haemophilus influenzae type b is a common cause of bacterial meningitis in children aged 6 years or older; empirical antibiotic therapy in this clinical situation should include treatment of this pathogen.

J Pediatr, 1990 Apr, 116(4), 529 - 38
Subnormal serum concentrations of IgG2 in children with frequent infections associated with varied patterns of immunologic dysfunction; Shackelford PG et al.; To characterize more fully the immunologic basis for increased susceptibility to infection in patients with low serum concentrations of IgG2, we identified eight infection-prone children, 1 to 2 years of age, with serum IgG2 concentrations greater than 2 SD below the mean for age and followed their serologic and clinical courses for 1 to 3 years . Two of the eight children became clinically and immunologically normal and may have had transient IgG2 deficiency with an exaggerated developmental delay of this late-maturing subclass . The remaining six subjects had persistently subnormal or low-normal serum IgG2 levels and continued to experience frequent infections . All six of these children responded poorly to Haemophilus influenzae type b (Hib) polysaccharide, and four of six responded poorly to Streptococcus pneumoniae type 3 polysaccharide . Both IgG1 and IgG2-specific antibody responses to these vaccines were abnormal . Three of these six children also responded poorly to tetanus toxoid, an antigen that normally induces a predominant IgG1 response . Although five of these six children produced antibodies in response to Hib polysaccharide protein conjugate vaccine, three of four given Hib oligosaccharide CRM conjugate vaccine required booster doses to respond, a pattern of response characteristic of infants less than 6 months of age . Further, although serum concentrations of IgG1 were normal, peripheral blood mononuclear cells from four of six children tested produced extremely small amounts of IgG1 and IgG3 as well as IgG2 . Finally, varied patterns of abnormalities of IgG, IgA, IgM, and IgG4 became apparent in five of the six children with persistently low serum IgG2 values . This study demonstrates that subnormal serum concentrations of IgG2 may be associated with varied patterns of immunologic dysfunction, some of which are evolving and may be responsible for increased susceptibility of these children to infection.

J Clin Invest, 1990 Apr, 85(4), 1158 - 66
A major crossreactive idiotype associated with human antibodies to the Haemophilus influenzae b polysaccharide . Expression in relation to age and immunoglobulin G subclass; Lucas AH et al.; Using idiotypic analysis, we examined the variable (V) region diversity of human antibodies specific for the capsular polysaccharide of Haemophilus influenzae b (Hib PS) . A goat anti-idiotypic serum (anti-Id) was prepared against anti-Hib PS antibodies isolated from the serum of an adult immunized with Hib PS . The anti-Id bound donor anti-Hib PS antibodies and inhibited Hib PS binding of donor anti-Hib PS . In contrast, the anti-Id did not bind donor or pooled Ig depleted of Hib PS antibodies, nor did it inhibit antigen binding of human antibodies to pneumococcal PS's, meningococcal A PS or diphtheria toxoid . Crossreactive idiotype (CRI), as measured by anti-Id inhibition of Hib PS binding, was found in 74 of 98 subjects (76%) vaccinated with Hib PS at 1.7-57 yr of age . 60 of these 74 subjects had greater than 50% of their serum Hib PS-binding activity inhibited by anti-Id . No correlation was found between age and CRI expression . In subjects showing both IgG1 and IgG2 antibody responses, CRI was most frequently detected in both subclasses (71% of subjects) . CRI was limited to either IgG1 or IgG2 in 19% of subjects, a finding suggestive of independent B cell lineages . 13 of 15 infants less than 17 mo of age, who responded to Hib PS-outer membrane protein conjugate vaccine, had greater than 50% of their serum anti-Hib PS antibody activity inhibited by anti-Id . The ability of native Hib PS and Hib PS oligomer to partially inhibit (60 and 35%, respectively) the binding between anti-Id and heterologous anti-Hib PS, indicated that some CRI determinants are in or near the combining site . In summary, our findings demonstrate a highly penetrant and frequently predominant CRI, which is expressed in both infants and adults . The results underscore the limited V region diversity of anti-Hib PS antibodies and indicate that CRI predominance is manifest early in ontogeny and is induced by both TI and TD forms of the Hib PS antigen.

Infect Immun, 1990 Apr, 58(4), 914 - 9
Multiple mechanisms in serum factor-induced resistance of Haemophilus influenzae type b to antibody; Kuratana M et al.; Incubation of Haemophilus influenzae type b at less than or equal to 10(7) CFU/ml with serum ultrafiltrate induces a phenotypic conversion in which complement-mediated bactericidal activity by somatic antibodies decreases while killing by capsular antibody is unchanged . Conversion had been shown to occur in a capsule-deficient (b-) mutant of strain Eag (thus appearing independent of capsulation), to include an increase in lipopolysaccharide content, and to be inhibited by chloramphenicol or puromycin . In the present study, in several strains not previously examined, conversion was not inhibited by the drugs and the corresponding b- mutants did not convert . Incubation in ultrafiltrate was also found to increase capsulation, as detected by radioassay, only 1.6-fold in Eag but 4.5-fold in DL26, the strain with the largest increase in resistance; moreover, complement-mediated opsonization by capsular antibody was greatly decreased . Thus, multiple mechanisms, capsule dependent as well as independent, appear to contribute to the serum factor-induced resistance of H . influenzae type b to antibody.

Microb Pathog, 1990 Apr, 8(4), 279 - 88
In vivo and in vitro expression of outer membrane components of Haemophilus influenzae; van Alphen L et al.; The outer membrane protein composition of Haemophilus influenzae grown under a variety of culture conditions including growth in sputum and serum, and intraperitoneally in rats was analyzed . The pattern of the major outer membrane proteins, a, b,c, d, e and P6 remained very similar under all these conditions . Outer membrane proteins expressed during iron limitation were also expressed in bacteria growing in rats, in serum or in sputum . To determine the expression of the major outer membrane proteins and lipopolysaccharide in patient materials (sputum, cerebrospinal fluid, postmortem tissue) monoclonal antibodies specific for the outer membrane proteins a, b,c, d and P6 as well as lipopolysaccharide were used in immunoblotting . They showed the same reaction patterns with bacteria in the patient materials as with the bacteria isolated from these specimens . We conclude that the major outer membrane components expressed under in vitro conditions are also expressed in various clinical materials during infection.

Avian Dis, 1990 Apr-Jun, 34(2), 267 - 76
Epidemiologic studies on infectious coryza outbreaks in northern New South Wales, Australia, using serotyping, biotyping, and chromosomal DNA restriction endonuclease analysis; Blackall PJ et al.; The epidemiology of 16 cases of infectious coryza, an upper respiratory tract disease of chickens caused by Haemophilus paragallinarum, was investigated in a retrospective study . The cases occurred over a 14-month period on 10 farms in northern New South Wales . The available field data indicated that the cases formed six unrelated outbreaks . The 16 isolates of H . paragallinarum were subjected to serotyping by the Page and Kume schemes and biotyping based on carbohydrate fermentation and antimicrobial drug-resistance patterns . As well, newer fingerprinting techniques--plasmid profiles, whole-cell protein profiles, immunoblots of whole-cell protein profiles and total DNA restriction endonuclease analysis (REA)--were evaluated . Antimicrobial biotyping and REA profile typing proved most useful, allowing the recognition of three groups among the isolates . The other techniques gave either limited or no subdivision among the isolates . The combined results of the laboratory study indicated that, rather than six unrelated outbreaks, the 16 isolates represented three pairs of related outbreaks . This study represents the first application of sensitive biotyping and fingerprinting techniques to outbreaks of infectious coryza . The results have established that farms can be repeatedly infected with a single strain of H . paragallinarum that re-emerges at intervals . This study also obtained the first detailed evidence that replacement stock are a major source of infectious coryza.

Can J Vet Res, 1990 Apr, 54 Suppl, S78 - 82
Our understanding of the Pasteurellaceae; Biberstein EL; With the exception of a few consistent pathogens--Pasteurella multocida strains of bovine hemorrhagic septicemia and fowl cholera, Actinobacillus (Haemophilus) pleuropneumoniae, Haemophilus aegyptius and Haemophilus paragallinarum--members of the family Pasteurellaceae are commensal parasites on mucous membranes of vertebrate animals . Many have pathogenic potential, which becomes manifest under conditions of immunodeficiency and stress . Pathogenesis (except in porcine atrophic rhinitis) depends on mobilization of inflammatory responses probably in large part by endotoxin with contributions from protein toxins, which interfere with leukocyte activity and, by their cytotoxicity, cause exacerbation of the inflammatory reaction . Disease patterns include pneumonic/septicemic, upper respiratory and local/traumatic . Acquired resistance is chiefly antibody-dependent, and, with current and emerging biotechnical resources, stands a good chance of being artificially achievable for many important diseases attributed to Pasteurellaceae.

Can J Vet Res, 1990 Apr, 54 Suppl, S73 - 7
Haemophilus, Actinobacillus, Pasteurella: mechanisms of resistance and antibiotic therapy; Willson PJ; Clinical isolates of members of the family Pasteurellaceae show resistance to drugs used for therapy of common infectious diseases of animals . Veterinarians want to use an antimicrobial that is effective against the pathogen, continues to provide therapy for several days, and is not too expensive . Resistant bacteria have complicated the problem of selecting the best antibiotics for treatment of livestock . Resistance to some antibiotics, such as those which inhibit ribosome function, may be encoded on the chromosome; however most antibiotic resistance that involves enzymatic pathways is mediated by genetic elements encoded on plasmids and/or transposons . Members of the genera Haemophilus, Actinobacillus and Pasteurella contain transferable plasmids and transposons that confer antibiotic resistance . This means that clones of pathogenic Pasteurellaceae have antibiotic resistance that fluctuates due to transferable plasmids as well as more permanent resistance mediated by chromosomal changes . Effective therapy requires treatment with a combination of long-acting agents.

Can J Vet Res, 1990 Apr, 54 Suppl, S68 - 72
New diagnostic techniques: a review of the HAP group of bacteria; Nielsen R; Pasteurella haemolytica, Pasteurella multocida, Haemophilus somnus, Haemophilus parasuis and Actinobacillus pleuropneumoniae cause considerable economic loss in the cattle and swine industries . The literature relating to diagnostic procedures for these infections is reviewed . Both conventional and newer techniques are appraised in relation to the identification and classification of isolates, and to serological testing.

Can J Vet Res, 1990 Apr, 54 Suppl, S63 - 7
Haemophilus influenzae: surface antigens and aspects of virulence; Munson RS Jr; Haemophilus influenzae type b is a major cause of bacterial meningitis and other invasive diseases in children under four years of age . One surface antigen, the type b capsular polysaccharide, polyribosylribitol phosphate (PRP), is a primary virulence factor of the organism . Antibody directed against PRP is protective; however, the purified polysaccharide is poorly immunogenic in young children . Polysaccharide-protein conjugate vaccines have been prepared which are significantly more immunogenic and efficacious in young children compared to the plain polysaccharide vaccine . Noncapsular surface antigens may also play a role in the virulence of H . influenzae . Some mutants (or phase variants) which differ in lipooligosaccharide (LOS) structure exhibit decreased virulence in the infant rat model of bacteremia . Proteins including the IgA protease, pili, a 98K outer membrane protein (OMP) as well as OMPs P1, P2 and P6 have also been examined in considerable detail, but whether they have a role in the virulence of the organism remains to be determined . However, antibody directed against the 98K OMP as well as P1, P2 and P6 is protective in the infant rat model of bacteremia . The role of antibody directed against LOS epitopes in protection is less clear, due at least in part, to phase variation in LOS antigens . Characterization of one surface antigen of H . influenzae type b, the capsular polysaccharide, already has led to the prevention of many cases of Haemophilus disease . Characterization of the noncapsular antigens together with a more detailed understanding of the mechanisms of virulence, most likely will permit development of even better vaccines, and possibly better treatment modalities, in the future.

Can J Vet Res, 1990 Apr, 54 Suppl, S57 - 62
Molecular aspects of some virulence factors of Haemophilus somnus; Corbeil LB; Several virulence factors of Haemophilus somnus have been investigated, but to a varying extent . It is known that some isolates are more virulent than others . Factors associated with virulence include attachment to vaginal epithelial cells, turbinate cells or embryos; serum resistance; growth stimulation by normal flora; interference with phagocyte function; Fc receptors; and toxicity for several bovine cell types . Lipooligosaccharide and Fc receptors have been investigated at the molecular level and studies are in progress to relate their molecular structure to virulence.

Can J Vet Res, 1990 Apr, 54 Suppl, S41 - 4
Positive and negative aspects of host immune response to Haemophilus, Actinobacillus and Pasteurella; Stephens LR; Haemophilus somnus, Actinobacillus pleuropneumoniae and Pasteurella haemolytica are economically important bacteria with pathogenic characteristics that require us to look further than killed, whole cell bacterins for induction of a protective immune response . A strong immune response is not synonymous with protection and the extreme specificity of the immune response works to our disadvantage when broad protection is needed . Detection of animals that are susceptible or immune to infection is important for the purpose of diagnosis and epidemiological study . However serum antibody levels are rarely indicative of protection unless it is known that the antibody of a particular isotype must be directed against a specific epitope for protection to occur . Parenteral vaccination with killed, whole cells of H . somnus, A . pleuropneumoniae or P . haemolytica produces, respectively, adequate protection, partial protection and increased disease . The reasons for these differences and methods of improving protection, based on an understanding of virulence determinants, are discussed.

Can J Vet Res, 1990 Apr, 54 Suppl, S36 - 40
Interactions of Haemophilus-Actinobacillus-Pasteurella bacteria with phagocytic cells; Czuprynski CJ et al.; The Haemophilus-Actinobacillus-Pasteurella (HAP) group of bacteria contains a number of important veterinary and human pathogens . Although each species has specific characteristics and host range, most share the general property of being resistant to cellular defense mechanisms . In some cases (e.g . Pasteurella multocida, Pasteurella haemolytica and Actinobacillus pleuropneumoniae) resistance results in part from the presence of an antiphagocytic capsule that protects the bacilli against ingestion by neutrophils and macrophages . In other instances the bacteria aggressively attack mononuclear and polymorphonuclear phagocytes . For example, P . haemolytica, A . pleuro-pneumoniae and Actinobacillus actinomycetemcomitans each produce a leukotoxin that functionally impairs, and ultimately kills, leukocytes from cattle, pigs and human beings, respectively . Components of Pasteurella multocida and Haemophilus somnus have also been reported to adversely affect leukocyte functions . Another important area of research that is just emerging concerns the ability of lipopolysaccharide and other components of HAP bacteria to stimulate or modulate macrophage release of inflammatory mediators such as interleukin-1 . In this paper, we provide an overview of the interactions of HAP bacteria with phagocytes and identify some of the common strategies by which they evade cellular defenses.

Can J Vet Res, 1990 Apr, 54 Suppl, S22 - 7
Capsules and virulence in the HAP group of bacteria; Inzana TJ; Many species in the genera Haemophilus, Actinobacillus, and Pasteurella produce serotype-specific, negatively-charged, polysaccharide capsules . In pure form, these capsules are nontoxic, relatively inert biologically, and some are poorly immunogenic . The capsule forms the outer-most surface of the bacterium, and prior to the development of specific antibody, inhibits the bactericidal and opsonic activity of normal serum . In contrast, noncapsulated isogenic mutants are generally avirulent, and are quickly cleared by host defenses . In conjunction with the bacterial cell, or through covalent conjugation to a protein carrier, relatively high titers of antibody to capsule can be produced in immunocompetent hosts . For some pathogens (such as H . influenzae type b) antibody to capsule alone is bactericidal, opsonic, and adequate for complete protection against disease . For pathogens that produce potent exotoxins, however, (such as P . haemolytica and A . pleuropneumoniae) antibody to capsule alone may provide only partial protection . The composition or structure of the capsule may also influence the relative virulence of a particular organism . Molecular analysis of the interaction between capsules and host defenses will be required to understand more fully how capsules influence bacterial virulence.

Scand J Immunol, 1990 Apr, 31(4), 515 - 22
Quantitation of antibody-secreting cells in the blood after vaccination with Haemophilus influenzae type b conjugate vaccine; Barington T et al.; The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level . In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide-specific antibody-secreting cells (AbSC) of the isotypes IgM, IgG, and IgA . The appearance of AbSC in the blood after vaccination of adults with diphtheria toxoid-conjugated Hib polysaccharide was investigated . AbSC were detected from post-vaccination day 5 to day 14 . IgA was the predominant isotype among these cells . IgM AbSC peaked slightly earlier (median day 7) than IgG and IgA AbSC (both day 8) . On post-vaccination day 8 the numbers of AbSC were: IgA, 1217/10(6) mononuclear cells (median); IgG, 211; and IgM, 30 (n = 11) . Similar isotype distribution has earlier been found after vaccination with pure capsular polysaccharides from Hib and pneumococci . The predominance of IgA AbSC in response to both conjugate and pure polysaccharide vaccines is probably due to reactivation of the same clones of IgA-committed memory B cells originally primed at the mucosa by natural exposure to the polysaccharide or cross-reacting antigens.

J Clin Microbiol, 1990 Apr, 28(4), 670 - 5
Rapid detection of bacteria in cerebrospinal fluid by immunofluorescence staining on membrane filters; Lim LC et al.; A filter-fluorescent-antibody (FFA) staining procedure was developed for detection of bacteria in cerebrospinal fluid (CSF) . The sensitivity of this procedure was determined and compared with that of the slide Gram stain of centrifuged samples, latex agglutination, and a previously developed filter Gram stain . Serial 10-fold dilutions of filter-sterilized CSF seeded with logarithmic-phase organisms were examined by each method and cultured to determine colony-forming bacteria . The bacteria included Haemophilus influenzae type b; Neisseria meningitidis group B, C, and W135; Streptococcus pneumoniae types 6A and 23F; and group B Streptococcus species . FFA was found to be equal in sensitivity to the filter Gram stain (P greater than 0.30) . Both filter-staining procedures had greater sensitivity than the slide Gram stain of centrifuged sediment (P less than 0.02) and latex agglutination (P less than 0.0001) . Addition of human leukocytes at a concentration of 5 to 10 cells per oil immersion field did not decrease sensitivity of the FFA procedure, although background fluorescence increased . FFA is a rapid and dependable procedure for detection of low numbers of bacteria in CSF . Evaluation of FFA with clinical specimens is needed.

Pediatrics, 1990 Apr, 85(4 Pt 2), 662 - 6
Passive immunization for infection with Haemophilus influenzae type b; Santosham M et al.; Haemophilus influenzae type b is the leading cause of meningitis in children younger than 5 years of age in the United States . The incidence of infection with H influenzae type b in certain populations, such as Apache and Navajo Indians and Alaskan Eskimos, is 10 to 20 times higher than in the general US population . Another important feature of H influenzae type b infections in these populations is that more than 80% of the cases occur during the first year of life, with 35% to 45% occurring during the first 6 months . One of the currently licensed vaccines that contains the capsular polysaccharide of the H influenzae type b organism is not reliably immunogenic in infants younger than 18 months of age . A number of new H influenzae type b vaccines prepared by covalently coupling the H influenzae type b capsular polysaccharide with a protein carrier antigen are undergoing clinical evaluation . One of these conjugate vaccines was shown to be efficacious in preventing disease caused by H influenzae type b in Finnish infants when they were immunized at 3, 4, and 6 months of age . Unfortunately, in a recently concluded trial, the same vaccine was not found to be efficacious in preventing such disease in infants younger than 1 year of age among the Alaskan Eskimo population . We have evaluated an alternative approach for protecting high-risk infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatrics, 1990 Apr, 85(4 Pt 2), 651 - 3
Clinical experience with Haemophilus influenzae type b conjugate vaccines; Makela PH et al.; The importance of Haemophilus influenzae type b as the main cause of serious bacteremic infections in young children and the consequent need for preventive measures have been widely appreciated since the 1970s . The knowledge that serum antibodies to the polysaccharide capsule of H influenzae type b increase with age and correlate with resistance to this infection encouraged work toward a vaccine based on the H influenzae type b polysaccharide . Such a vaccine was used in 1974 in a field trial in Finland . Two important lessons were learned . First, vaccine-induced antibodies to the polyribosylribitol-phosphate (PRP) polysaccharide correlated with protection from disease caused by H influenzae type b, so that the serum anti-PRP concentration predicting protection could be estimated as 1 microgram/mL . Second, the vaccine was not effective in infancy; protection and serum antibody concentrations above 1 microgram/mL were not observed before 18 to 24 months of age . The poor immunogenicity of PRP in infancy has been observed in a large number of studies and is shared by other bacterial polysaccharides . Although the reason for this is not known, the most likely hypothesis associates poor immunizing ability in infancy with the "T-independent" nature of these polysaccharide antigens . Such antigens would be unable to stimulate T lymphocytes; therefore, immunity to them would depend exclusively on B cells and antibodies produced by them . If infants, by and large, lack B cells that could be stimulated directly by a polysaccharide antigen, they cannot respond to the polysaccharide vaccine . This hypothesis immediately suggests possibilities for improvement of the vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatrics, 1990 Apr, 85(4 Pt 2), 643 - 7
Protective efficacy of Haemophilus influenzae type b polysaccharide vaccine; Shapiro ED et al.; There has been uncertainty and controversy about the protective efficacy of Haemophilus influenzae type b polysaccharide vaccine almost since it first was licensed in the United States . This article will briefly review the available epidemiologic data about the protective efficacy of this vaccine in children with no recognized underlying illnesses . H influenzae type b polysaccharide vaccine was licensed in the United States in April 1985, based on the results of a randomized clinical trial that was conducted in Finland . That study indicated that the vaccine's protective efficacy was 90% against invasive disease caused by H influenzae type b in children 18 to 71 months of age . Authorities recommended that all children receive the vaccine at 2 years of age and that it be administered to children up to the age of 60 months . The Immunization Practices Advisory Committee also recommended that children at increased risk (such as those who attend group day care) receive the vaccine at 18 months and again at 24 months of age because of its inconsistent immunogenicity when administered to 18-month-old children . Soon after its licensure, however, reports of vaccine failures began to appear . In some instances the vaccine failure could be attributed to an identifiable immune deficiency . However, Granoff et al reported 54 apparently normal children who had received the H influenzae type b polysaccharide vaccine but subsequently developed invasive disease caused by H influenzae type b . The majority of these children had normal serum concentrations of total immunoglobulins, IgG2, hemolytic complement, and antibody to tetanus toxoid (a T-cell-dependent antigen).(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatrics, 1990 Apr, 85(4 Pt 2), 636 - 42
Molecular epidemiology of Haemophilus influenzae type b; van Alphen L et al.; Ninety-five percent of systemic Haemophilus influenzae infections in childhood are caused by serotype b organisms . The high risk for mortality and serious sequelae and the increase in antibiotic resistance of H influenzae type b are strong arguments for vaccination . Incidences and age distribution of disease caused by H influenzae type b vary considerably among countries . Compiled data for meningitis show the highest incidences to be among Alaskan Eskimos, Navajo and White Mountain Indians, and aboriginals in Australia . High incidences coincide with a peak incidence in a younger age group . This differs from Finland, where 95% of the cases of disease caused by H influenzae type b occur in children older than 7 months of age . In general, incidences are low in industrial and high in nonindustrial areas . For example, in Gambia the highest age-specific incidence is at 4 to 5 months after birth (H.A.B., unpublished data, 1988) . This implies that a vaccine and regimen similar to that used in Finland would not be as efficacious if used in Gambia because of differences in demographics and incidence . Vaccines that confer protection at 3 to 4 months of age are, therefore, strongly desired . Outer membrane proteins and lipopolysaccharides of H influenzae type b have been suggested as alternative vaccine candidates in conjugation with the capsular polysaccharide because they apparently can contribute to the virulence of H influenzae type b . The occurrence and immunogenicity of various outer membrane proteins and lipopolysaccharides among H influenzae type b in industrial and nonindustrial countries and their significance as epidemiologic markers for the spread of disease, the type of disease, the age of acquisition, and their association with antibiotic resistance will be reviewed in this article.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatrics, 1990 Apr, 85(4 Pt 2), 631 - 5
Epidemiology of Haemophilus influenzae type b infections; Wilfert CM; Haemophilus influenzae type b is a human bacterial pathogen that causes approximately 12,000 cases of H influenzae type b meningitis and 7500 cases of other forms of invasive disease annually in the United States . This organism is the leading cause of bacterial meningitis in the United States . The cause of meningitis can be established more accurately than that of other forms of invasive bacterial disease because the isolation of the bacterium from the cerebrospinal fluid or blood and/or the detection of bacterial antigen can correctly attribute the infection to a specific bacterial agent and dictate appropriate antimicrobial therapy . In children, more than 95% of all invasive diseases attributable to Haemophilus species, including septicemia, pneumonia, epiglottis, cellulitis, arthritis, osteomyelitis, and pericarditis, are due to H influenzae type b . It has been estimated that systemic disease caused by H influenzae type b occurs in approximately 1 in 200 children in the United States before the age of five . The case fatality rate for H influenzae type b meningitis is approximately 5%, and substantial morbidity has also been documented to result from central nervous system infection with this agent . Of surviving children reported in a 1969 paper, 40% had significant neurologic sequelae after meningitis . A more recent study demonstrated substantial neurologic improvement during the first few months after hospitalization, but at 1 year of age 8% of the children had neurologic or intellectual sequelae of their meningitis . Milder defects with an array of developmental problems have been reported in as many as one third to one half of all survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antimicrob Chemother, 1990 Apr, 25(4), 535 - 9
In-vitro activities of trospectomycin, cefpodoxime, and second-generation cephalosporins against Haemophilus influenzae type b; LiPuma JJ et al.; The in-vitro activities of trospectomycin, cefpodoxime, cefamandole, cefonicid, and cefuroxime against beta-lactamase-negative and -positive invasive clinical isolates of Haemophilus influenzae type b were determined by the agar dilution method . Trospectomycin and cefpodoxime inhibited 90% of the strains at concentrations of 5 and 0.06 mg/l, respectively, and no differences between the susceptibilities of the beta-lactamase-negative and -positive strains were noted . The activity of cefpodoxime was minimally affected by increased inoculum size, but significant inoculum effects were noted with cefamandole, cefonicid, and cefuroxime with beta-lactamase positive strains.

Acta Paediatr Jpn, 1990 Apr, 32(2), 132 - 8
Antibiotic susceptibility of type b Haemophilus influenzae and Streptococcus pneumoniae, and antibiotic concentration in cerebrospinal fluid; Fujita K et al.; Antibiotic susceptibilities of 38 type b Haemophilus influenzae and 28 Streptococcus pneumoniae strains isolated from cerebrospinal fluid, blood and other specimens between 1973 and 1988 were studied . Minimal inhibitory concentrations (MICs) of ampicillin against 10 beta-lactamase positive and 28 negative H . influenzae isolates were 32-64 and 0.25 micrograms/ml, respectively . The MIC of chloramphenicol against one of the beta-lactamase positive H . influenzae strains was 8 but MICs against the rest of the organisms were 0.5-1 micrograms/ml . MICs of cefotaxime, ceftriaxone and cefuroxime against all H . influenzae strains were 0.016, 0.008 and 0.5 micrograms/ml, respectively . No S . pneumoniae isolates were resistant to penicillin G and MICs of this drug were 0.016-0.032 micrograms/ml . MICs of cefotaxime, cefriaxone and cefuroxime against all S . pneumoniae strains were 0.016-0.032, 0.016-0.032 and 0.032-0.063 micrograms/ml, respectively . MICs of chloramphenicol against 15, 4 and 9 of S . pneumoniae isolates were 2, 8 and 16 micrograms/ml, respectively . Antibiotic concentrations in the cerebrospinal fluid of patients with bacterial meningitis after intravenous administration of ampicillin (50-70 mg/kg x 4/day), penicillin G (31-63 mg/kg x 4/day), cefotaxime (50 mg/kg x 4/day) and chloramphenicol (25 mg/kg x 4/day) were 4.70 +/- 1.83 (n = 11), 0.57 +/- 0.32 (n = 7), 4.97 +/- 2.60 (n = 9) and 8.52 +/- 3.54 micrograms/ml (n = 3), respectively . The initial choice of antibiotics in older children with bacterial meningitis is a combination of ampicillin (75 mg/kg x 4/day) and cefotaxime (50 mg/kg x 4/day) to cover ampicillin-resistant H . influenzae, S . pneumoniae, and Listeria monocytogenes in Japan . These antibiotics should be changed according to the causative organisms and their antibiotic susceptibilities.

Thorax, 1990 Apr, 45(4), 276 - 80
Effect of bacterial products on neutrophil migration in vitro; Ras G et al.; Chronic bronchial inflammation is associated with migration of large numbers of granulocytes into the bronchial tree . A study was designed to find out whether products of bacteria commonly isolated in chronic bronchial infection stimulate neutrophil migration in vitro . Neutrophils from healthy donors were studied by a modified Boyden chamber technique . Bacterial culture filtrates stimulated neutrophil migration over a wide dilution range and the chemotactic activity was heat stable . Culture filtrates derived from Pseudomonas aeruginosa, Streptococcus pneumoniae, and Haemophilus influenzae were significantly chemokinetic and directionally chemotactic, whereas filtrates from Staphylococcus aureus were only chemotactic . Gel filtration of S aureus and P aeruginosa culture filtrates yielded high, medium, and low molecular weight fractions showing chemotactic activity . S pneumoniae and H influenzae yielded fractions with only low molecular weight chemotactic activity . Neutrophil chemotactic responses, occurring in response to all bacterial species tested, appear to represent a defence mechanism by the host . Chemoattractant activity may, however, contribute to bronchial damage mediated by products released from continuously attracted, activated neutrophils.

Eur J Clin Microbiol Infect Dis, 1990 Apr, 9(4), 278 - 81
Bacterial counts in cerebrospinal fluid of children with meningitis; Bingen E et al.; Eighty-five cerebrospinal fluid (CSF) specimens from the same number of pediatric patients with meningitis were examined to determine the bacterial count and the relationship of this count to the microscopy results, the ages of the patients and the bacterial species isolated . Bacterial counts ranged from 2 x 10 to 4 x 10(9) CFU/ml CSF . Twenty-five percent of the 85 CSF specimens positive for Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli K1 and group B streptococci had counts of 10(7) CFU/ml or higher . Children between 1 and 6 months of age had significantly higher counts (p less than 0.05) than the other age groups . The three patients who had positive CSF cultures 24 h after the start of therapy all had initial bacterial counts of 10(7) CFU/ml or higher . The detection limit for Gram stain/microscopy was 10(5) CFU/ml . No correlation was found between bacterial count and the number of polymorphonuclear leukocytes.

Vaccine, 1990 Apr, 8(2), 107 - 10
Reactogenicity and immunogenicity of combined vaccines for bacteraemic diseases caused by Haemophilus influenzae type b, meningococci and pneumococci in 24-month-old children; Eskola J et al.; To find a wide spectrum vaccine against bacteraemic disease in childhood, we immunized 293 Finnish children at 24 months of age intramuscularly with different combinations of the currently available vaccines, namely Haemophilus influenzae type b polysaccharide-protein conjugate vaccine (PRP-D) mixed with meningococcal and/or pneumococcal capsular polysaccharide vaccines . All the vaccines were immunogenic . The increase in antibody concentration after vaccinations was not affected by the number of polysaccharide antigens . Although no serious reactions were seen, the frequency of both local and fever reactions was greater in groups that received several vaccine antigens . Halving of the vaccine dose decreased the reactogenicity without impairing the immunogenicity.

Pediatr Infect Dis J, 1990 Apr, 9(4), 246 - 52
Cost-benefit analysis of Haemophilus influenzae type b prevention: conjugate vaccination at eighteen months of age; Hay JW et al.; A cost-benefit analysis of Haemophilus influenzae type b disease preventive strategies was updated to consider evaluation of the H . influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) and H . influenzae type b oligosaccharide-mutant diphtheria toxin conjugate vaccine (HbOC) for children at 18 months of age . The analysis was done from the perspective of society as a whole . The economic costs of H . influenzae type b disease in the 1988 United States birth cohort would be $2.546 billion (1988 U.S . dollars) in the absence of preventive efforts . If 60% of all children could be vaccinated with PRP-D or HbOC at 18 months of age, this strategy would save $207.1 million ($88.22 savings/vaccinee; $43,605 cost/case prevented; 3.57/1 benefit-to-cost ratio) under base case model assumptions . Universal PRP-D or HbOC vaccination at 18 months of age would prevent 1845 cases of invasive H . influenzae type b disease . The break-even efficacy for universal PRP-D or HbOC vaccination at 18 months of age was 22.7% . We conclude that, under the model base case assumptions, universal PRP-D or HbOC vaccination at 18 months of age is sufficiently efficacious so that the costs of vaccination would be more than offset by decreased medical care costs for treating H . influenzae type b disease.

CMAJ, 1990 Apr 1, 142(7), 719 - 33
Effectiveness of Haemophilus influenzae type b vaccines; Stieb DM et al.; PURPOSE: To determine the clinical effectiveness of Haemophilus influenzae type b (Hib) vaccines . STUDY IDENTIFICATION AND SELECTION: Computerized searches of MEDLINE, EMBASE and SCISEARCH databases were performed, and the reference list of each retrieved article was reviewed . Two prospective clinical trials of Hib polyribosyl ribitol phosphate conjugated with diphtheria toxoid (PRP-D) were identified . In addition, one cohort study of the PRP-D vaccine, two trials of the PRP vaccine, five case-control studies of the PRP vaccine and 10 randomized controlled trials of the immunogenicity of the PRP-D vaccine were identified . DATA EXTRACTION: Study quality was assessed and descriptive information concerning the study populations, the interventions and the outcome measurements was extracted . RESULTS: The difference in the effectiveness of the PRP-D vaccine between the prospective trials, in which a three-dose schedule had been used beginning at 2 to 3 months of age, was clinically important (37% v . 83%) but not statistically significant . The PRP vaccine, which induces lower antibody responses than the PRP-D vaccine does, was clinically effective only in a subgroup of one prospective trial; 90% effectiveness was reported among children 18 to 60 months of age . CONCLUSIONS: Hib vaccine appears to be less effective in high-risk populations . None the less, because of the large variation in baseline risk, the number of children who would have to be vaccinated to prevent one case of invasive Hib disease is substantially less for high-risk than for low-risk populations . The vaccination of children at high risk, such as native children, with the PRP-D vaccine using a four-dose schedule (at 2, 4, 6 and 14 months of age) seems warranted . The currently available evidence does not strongly support a policy of universal vaccination with either a one-dose or a four-dose schedule.

Pediatrics, 1990 Apr, 85(4 Pt 2), 698 - 704
Disease caused by Haemophilus influenzae type b in the immediate period after homologous immunization: immunologic investigation; Sood SK et al.; Several Haemophilus influenzae type b vaccines have been licensed and recommended for administration to children in the United States . These vaccines have consisted of purified polyribosylribitol-phosphate (PRP), the capsular polysaccharide of H influenzae type b, alone or covalently bound to one of several carrier proteins . Two of these saccharide-protein conjugate vaccines are now licensed, a polysaccharide-diphtheria toxoid conjugate (PRP-D) and an oligosaccharide-mutant diphtheria toxin conjugate (HbOC) . Two others, a polysaccharide-Neisseria meningitidis outer membrane protein conjugate (PRP-OMPC) and a polysaccharide-tetanus toxoid conjugate (PRP-T), are currently in clinical trials . One concern with the use of PRP vaccine was the suggestion that the incidence of invasive disease caused by H influenzae type b in the immediate period after immunization might be increased; this idea was supported by evidence from several sources . In a case-control study of the efficacy of PRP vaccine, Black et al found that 4 children were hospitalized for invasive disease within 1 week of immunization, a rate of invasive disease 6.4 times greater (95% confidence interval {CI}, 2.1 to 19.2) than the background rate in unvaccinated children . In Minnesota, the relative risk for invasive disease in the first week after immunization was 6.2 (95% CI, 0.6 to 45.9), and the results of a study conducted by the Centers for Disease Control in six areas of the United States revealed a 1.8-fold (95% CI, 0.3 to 10.2) increase in the occurrence of invasive disease caused by H influenzae type b in the first week after immunization.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatrics, 1990 Apr, 85(4 Pt 2), 694 - 7
Opsonophagocidal activity in sera from infants and children immunized with Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate); Gray BM; Immunization with Haemophilus influenzae type b capsular polysaccharide (polyribosylribitol-phosphate {PRP}) has resulted in limited and variable antibody radioimmunoassay in infants younger than 2 years of age . Although an H influenzae type B vaccine has been in use for several years, it is not used now for the age group at greatest risk for disease . In an effort to enhance immunogenicity, PRP has been coupled to various carrier proteins and to an outer membrane protein complex (OMPC) from Neisseria meningitidis group B . The latter approach has yielded a vaccine that elicits a good antibody response after a single 15-micrograms dose of vaccine in infants as young as 2 months of age, as measured by radioimmunoassay and immune bacteriolysis . In this report we describe the results of a pilot study using this H influenzae type B conjugate vaccine, PedvaxHIB, in children from 2 months to 4 years of age . Three different vaccine lots were examined for consistency of response . Sera were measured for antibody levels by radioimmunoassay and for functional activity using an opsonophagocytic assay using human adult neutrophils . These assays correlated well and demonstrated the excellent immune response and biologic activity of sera from infants vaccinated with this unique H influenzae type B conjugate vaccine.

Pediatrics, 1990 Apr, 85(4 Pt 2), 690 - 3
Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate): immunogenicity and safety at various doses; Yogev R et al.; The Haemophilus influenzae vaccine consisting of purified type b capsular polysaccharide (polyribosylribitol-phosphate {PRP}) was shown in Finland to be protective, with 90% efficacy in children older than 18 to 23 months of age . However, a wide range of estimates of vaccine efficacy has been reported in the United States after its licensure in 1985 . These estimates range from -55% to +89% . In addition, the PRP vaccine was not effective in children younger than 18 months of age, in whom 70% to 80% of meningitis cases occur . A further development was the introduction of H influenzae type b polysaccharide-protein conjugate vaccines such as the PRP-D . These conjugate vaccines were found to be more immunogenic than PRP vaccine in children of all ages . Two doses of PRP-D in infants 7 months of age and older induced antibody levels equal to or greater than levels in infants 24 months of age who received the PRP vaccine alone . Recently, Eskola et al reported that repeat vaccinations with PRP-D at 3, 4, 6, and 14 months of age was 83% protective (95% confidence interval, 26% to 96%) . Yet PRP-D vaccine elicits only low serum antibody levels in infants younger than 7 months of age . Because of the discrepancy in efficacy results for the PRP vaccine in the United States and Finland and the lack of data about the protective efficacy of PRP-D vaccine in infants in the United States, the PRP-D vaccine is currently recommended only for children 18 months of age or older.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatrics, 1990 Apr, 85(4 Pt 2), 682 - 9
Safety, tolerability, and immunogenicity of concurrent administration of Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) with either measles-mumps-rubella vaccine or diphtheria-tetanus-pertussis and oral poliovirus vaccines in 14- to 23-month-old infants; Dashefsky B et al.; In 1985, the first capsular polysaccharide (polyribosylribitol-phosphate {PRP}) vaccine for Haemophilus influenzae type b was licensed and recommended for routine use in children between 24 and 60 months of age . In the United States, approximately 75% to 90% of invasive disease due to H influenzae type b occurs in infants younger than 24 months, a population for whom H influenzae type b polysaccharide vaccine is inadequately immunogenic and protective . In an effort to enhance the immunogenicity of H influenzae type b polysaccharide vaccine for children in the most susceptible age groups, conjugate vaccines have been developed in which the capsular PRP of H influenzae type b has been bound to a variety of carrier proteins, thereby conferring the vaccines with thymic-dependent attributes . One such conjugate vaccine, in which the carrier protein is diphtheria toxoid (PRP-D), was licensed in 1987 and has been recommended since 1988 for routine use in children 18 months of age and older . A second conjugate vaccine, in which an oligosaccharide derivative of H influenzae type b capsular PRP is coupled to CRM, a nontoxic mutant diphtheria toxin (oligo-CRM), was licensed in 1988 and is a sanctioned alternative to PRP-D . Another investigational conjugate vaccine, in which the polysaccharide is linked to the outer membrane protein of Neisseria meningitidis group B (PRP-OMPC), has been demonstrated to be both safe and immunogenic when administered in a two-dose schedule to 2- to 6-month-old infants . However, anti-PRP antibody levels decline significantly during the ensuing 10 to 15 months; they rise significantly in response to booster doses of either PRP or PRP-OMPC administered 10 to 15 months after the initial priming doses of PRP-OMPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatrics, 1990 Apr, 85(4 Pt 2), 676 - 81
Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB): clinical evaluation; Ahonkhai VI et al.; Although systemic infections caused by Haemophilus influenzae type b occur worldwide, detailed epidemiologic data are available in but a few countries . The public health impact of morbidity, mortality, and serious sequelae from disease caused by H influenzae type b has stimulated the search for control strategies . In the United States now, active immunoprophylaxis is largely favored over treatment of prophylaxis with antibiotics . This preference stems from three major observations: that high mortality and morbidity persist despite the availability of potent antimicrobial agents, that antibiotic-resistant strains of H influenzae type b have emerged, and that implementation of antimicrobial prophylaxis on a large scale has been unsatisfactory . Moreover, universal vaccination has been projected as offering a higher economic benefit than other control strategies . A matter of more proximate importance, however, is the search for H influenzae type b vaccines that will confer protection to all age groups, including infants younger than 18 months of age and subpopulations specifically at risk for invasive disease caused by H influenzae type b . Haemophilus b conjugate vaccine (meningococcal protein conjugate), PedvaxHIB (PRP-OMPC), is a conjugate H influenzae type b vaccine developed at Merck Sharp & Dohme Research Laboratories that now is undergoing extensive clinical evaluation to assess its prospects for disease control when first administered in early infancy . This is an interim report of results obtained in studies conducted in diverse locations throughout the United States.

Pediatrics, 1990 Apr, 85(4 Pt 2), 668 - 75
Immunogenicity of a new Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB); Vella PP et al.; Haemophilus influenzae type b is responsible for an estimated 15,000 to 20,000 cases of meningitis per year in the United States, mainly in children 2 months to 5 years old . The mortality rate from meningitis due to H influenzae type b infections ranges from 5% to 10% . Despite antibiotic treatment, up to 35% of survivors have permanent neurologic sequelae . In addition to meningitis, H . influenzae type b is responsible for other invasive infections, including epiglottitis, septicemia, cellulitis, septic arthritis, osteomyelitis, pneumonia, pericarditis, and otitis media; approximately 30,000 cases H influenzae diseases occur annually in the United States . The diseases peak in incidence between 6 and 12 months of age, with almost one half of the cases occurring before 1 year of age . About 75% of disease caused by H influenzae type b occurs in children younger than 24 months old . The incidence of disease is higher in children of certain groups, including blacks, Hispanics, Eskimos and Native Americans, young children attending day-care facilities, patients with asplenia or antibody-deficiency syndromes, and children of lower socioeconomic status . There is considerable evidence that antibody to the capsular polysaccharide (polyribosylribitol-phosphate {PRP} of H influenzae type b is protective.(ABSTRACT TRUNCATED AT 250 WORDS)

J Vet Diagn Invest, 1990 Apr, 2(2), 116 - 9
Monoclonal antibody in the identification of Haemophilus somnus; Thomson MS et al.; Electrophoretic comparisons of outer membrane proteins of Haemophilus somnus isolates revealed 2 major protein bands (46 and 14 kilodaltons {kD}) common to all isolates tested . A monoclonal antibody raised against H . somnus reacted to the 46-kD band . Coagglutination tests were performed using a monoclonal antibody coagglutination assay . The monoclonal reagent was produced by incubating Cowan strain Staphylococcus aureus suspension, used as a source of crude protein A, with mouse ascitic fluid monoclonal antibody or goat anti-H . somnus hyperimmune serum . Bacteria to be tested were suspended at a concentration of 4.5 x 10(9) cells/ml . The coagglutination test was performed by the addition of 50 microliters of the monoclonal reagent to 50 microliters of the bacterial suspension on a glass plate and manual rotation for 2-3 minutes . The coagglutination assay using Cowan strain Staphylococcus aureus protein A, coupled with the monoclonal antibody, agglutinated 10 different H . somnus isolates . The antibody reagent did not coagglutinate with Actinobacillus suis, A . equuli, Pasteurella haemolytica, P . multocida, or P . pneumotropica under similar test conditions.

J Hosp Infect, 1990 Apr, 15 Suppl A, 35 - 9
The emergence of bacterial resistance in hospitals--a need for continuous surveillance; Brown EH et al.; The antibiotic sensitivities of a total of 220,000 isolates from 44 hospitals collected over 2.5 years were monitored by computer . Gram-negative organisms account for 63% of the total, the most common being Escherichia coli (43%) . Staphylococcus aureus was the most frequently isolated Gram-positive organism (44%) . The organism most commonly isolated from blood was E . coli; this organism was susceptible to ceftazidime (100%), ampicillin (47%), gentamicin (99%) and co-trimoxazole (85%) . The organism most frequently isolated from sputum was Haemophilus influenzae; this organism was susceptible to ceftazidime (99%), cefuroxime (99%), ampicillin (89%) and erythromycin (78%) . A 15-fold increase in the use of ceftazidime over the past 4 years has not been accompanied by increased resistance in common pathogens . Analysis shows that the susceptibility of E . coli and Pseudomonas aeruginosa to ceftazidime has remained constant throughout the duration of this survey . The data collected from this type of survey can be used to determine local trends in antibiotic susceptibility and hence aid the rational use of antibiotics in hospitals.

J Clin Microbiol, 1990 Apr, 28(4), 756 - 63
Purification and characterization of a pilin specific for Brazilian purpuric fever-associated Haemophilus influenzae biogroup aegyptius (H . aegyptius) strains; Weyant RS et al.; Brazilian purpuric fever (BPF) is a recently described fatal pediatric disease caused by systemic infection with Haemophilus influenzae biogroup aegyptius . Previous studies have shown that all H . influenzae biogroup aegyptius strains isolated from BPF cases and case contacts share several unique phenotypic and genotypic characteristics that differentiate them from other H . influenzae biogroup aegyptius strains isolated from conjunctivitis cases in Brazil . One key characteristic of this BPF clone is reactivity in a BPF-specific monoclonal antibody enzyme-linked immunosorbent assay . We have purified and partially characterized a pilin, referred to as the 25-kilodalton (kDa) protein . Aggregates of this protein contain a heat-labile epitope which is recognized by a monoclonal antibody used in the BPF-specific enzyme-linked immunosorbent assay . The protein has a molecular weight of approximately 25,000, is insoluble in most detergents, and fractionates with outer membrane vesicles after LiCl extraction . Biochemical analysis of the 25-kDa protein shows it to have an amino acid composition similar but not identical to that of the H . influenzae type b pilin . The sequence of 20 N-terminal amino acids of the 25-kDa protein shows almost complete homology with the N terminus of the H . influenzae type b pilin and the types 1 and P pilins of Escherichia coli . Transmission electron microscopic analysis of the purified protein shows the presence of filamentous structures similar in morphology to those of H . influenzae pili . Reactivity between the 25-kDa protein and the BPF-specific monoclonal antibody is demonstrated by Western blotting (immunoblotting) and colloidal gold-enhanced immunoelectron microscopy . Hemadsorption analysis shows that expression of this protein is associated with increases in piliated cells and enhanced binding of these cells to human erythrocytes . These studies indicate that expression of the 25-kDa protein is a characteristic unique to the BPF clone and suggest that this protein plays a role in the pathogenesis of BPF.

Infect Immun, 1990 Apr, 58(4), 1065 - 72
Cloning, expression, and sequence analysis of the Haemophilus influenzae type b strain M43p+ pilin gene; Gilsdorf JR et al.; By using antiserum against Haemophilus influenzae type b (Hib) strain M43p+ denatured pilin, we screened a genomic library of Hib strain M43p+ and identified a clone that expressed pilin, but not assembled pili, on its surface . Southern blot analysis revealed the presence of one structural gene, which was also present in strain M42p-, a nonpiliated variant . Five exonuclease III deletion mutants, two of which had deletions that extended into the structural gene and failed to express pilin, were used to obtain the nucleotide sequence of the structural gene . The amino acid sequence of the open reading frame agrees with 38 of 40 amino acids from the published sequence of purified Hib M43p+ pilin . The pilin gene coded for a mature protein of 193 amino acids, with a calculated molecular mass of 21,101 daltons . Comparison of the Hib M43p+ pilin amino acid sequence with those of pilins of other bacteria revealed strong conservation of amino- and carboxy-terminal regions in M43p+ and Escherichia coli F17, type 1C, and several members of the P pili family, as well as Klebsiella pneumoniae type 3 MR/K, Bordetella pertussis serotype 2, and Serratia marcescens US46 fimbriae.

Biochem Cell Biol, 1990 Apr, 68(4), 808 - 10
Structural analysis of the lipopolysaccharide of Actinobacillus (Haemophilus) pleuropneumoniae serotype 10; Perry MB; The antigenic O-chain of the lipopolysaccharide produced by Actinobacillus (Haemophilus) pleuropneumoniae serotype 10 was shown by chemical and magnetic resonance methods to be a unique linear unbranched homopolymer of exclusively 1,2-linked beta-D-galactofuranose residues.

Agents Actions, 1990 Apr, 30(1-2), 57 - 60
Haemophilus influenzae potentiates basophil histamine release possibly by its endotoxins; Norn S et al.; Haemophilus influenzae and its extracellular products (EP) did not release histamine in leukocyte suspensions from normal individuals . However, the EP were found to enhance basophil histamine release triggered by anti-IgE and by the calcium ionophore A23187 . Experiments with EP indicate that it is the content of endotoxins which is responsible for the potentiating effect . Removal of endotoxin from the EP thus completely abolished the potentiating effect, whereas inactivation of its protease and proteins by heat-treatment or by proteinase K did not change the potentiation . A reinforcement of mediator release by the extracellular products of H . influenzae might play a pathophysiological role in chronic obstructive pulmonary disease.

Can J Vet Res, 1990 Apr, 54 Suppl, S6 - 11
The family Pasteurellaceae: modern approaches to taxonomy; MacInnes JI et al.; Historically, members of the family Pasteurellaceae were classified on the basis of a limited number of phenotypic characteristics . In particular, organisms were assigned to the family on the basis of their requirements for the growth factors hemin and/or nicotinamide adenine dinucleotide and on the basis of their ability to cause disease in vertebrates . More recent genotypic studies have shown that many members of the family Pasteurellaceae have been misclassified . In this paper we review some of the current taxonomic methods which can be used to emend the classification of Haemophilus, Actinobacillus and Pasteurella spp . and suggest some approaches and criteria for restructuring the family Pasteurellaceae.

Gene, 1990 Mar 30, 88(1), 1 - 5
Construction of an efficient overproducer clone of HinfI restriction endonuclease using the polymerase chain reaction; Skoglund CM et al.; We describe the use of the polymerase chain reaction (PCR) technique to alter transcriptional and translational signals surrounding a gene so as to achieve overexpression in Escherichia coli . By changing the ribosome-binding site sequence preceding the hinfIR gene to match the consensus E . coli signal and by adding a transcription terminator sequence immediately following the gene, the yield of HinfI was increased about tenfold over that obtained from the natural Haemophilus influenzae signals . The addition of the positive retroregulator stem-loop sequence derived from the crystal protein-encoding gene of Bacillus thuringiensis downstream from the hinfIR gene further increased yields by twofold to a level of 13% of the total cellular protein.

Nucleic Acids Res, 1990 Mar 25, 18(6), 1377 - 83
Cloning and characterization of the HpaII methylase gene; Card CO et al.; The HpaII restriction-modification system from Haemophilus parainfluenzae recognizes the DNA sequence CCGG . The gene for the HpaII methylase has been cloned into E . coli and its nucleotide sequence has been determined . The DNA of the clones is fully protected against cleavage by the HpaII restriction enzyme in vitro, indicating that the methylase gene is active in E . coli . The clones were isolated in an McrA-strain of E . coli; attempts to isolate them in an McrA+ strain were unsuccessful . The clones do not express detectable HpaII restriction endonuclease activity, suggesting that either the endonuclease gene is not expressed well in E . coli, or that it is not present in its entirety in any of the clones that we have isolated . The derived amino acid sequence of the HpaII methylase shows overall similarity to other cytosine methylases . It bears a particularly close resemblance to the sequences of the HhaI, BsuFI and MspI methylases . When compared with three other methylases that recognize CCGG, the variable region of the HpaII methylase, which is believed to be responsible for sequence specific recognition, shows some similarity to the corresponding regions of the BsuFI and MspI methylases, but is rather dissimilar to that of the SPR methylase.

Tijdschr Diergeneeskd, 1990 Mar 15, 115(6), 249 - 61
{Log book registration of farms for slaughtering pigs in the Integrated Quality Control Project . I . Use of drugs and vaccines}; Elbers AR et al.; Log book recording was done for twelve months on approximately 100 pig finishing farms in an Integrated Quality Control (IQC) project . This recording was designed to gain a better understanding of the extent and nature of the medication and vaccination on these farms . Vaccination against Aujeszky's disease was done on the majority of farms . This vaccination mainly consisted in a single, frequently intramuscular, injection . Vaccinations against swine influenza and infections due to Actinobacillus (Haemophilus) pleuropneumoniae were merely sporadic . The animals were dewormed in 58 per cent of the finishing periods, whereas they were given preventive treatment for sarcoptic mange in 23 per cent of the finishing periods . Not a single pig was treated with antibiotics and/or chemotherapeutic agents in 12.5 per cent of the finishing periods . The majority of finishing periods in which treatment was not carried out, were those having closed pig herds . To the extent that the farms were supplied with piglets by more breeders, there were fewer finishing periods during which treatment was omitted . The great majority of cases in which individual therapy was given, were treated for respiratory disorders . On 27 per cent of the farms, more than 10 per cent of the animals per finishing period were treated for respiratory disorders . Group medication was much less frequent: intestinal disorders did not have to be treated on 31 per cent of the farms, and 16 per cent did not require treatment for respiratory disorders . In the great majority of cases in which group treatment was required, this was given during the first sixty days of the finishing period . In view of the fact that there are marked differences in the degree to which pigs have to be medicated on the farms, recording the use of veterinary drugs on farms, could fulfil the function of a signal . On the basis of these signals, measures may be suggested in herd management programmes to ensure an effective and minimum use of veterinary drugs . Using a log book will also enable the pig farmer to estimate whether groups of animals may be sent to the slaughter-house without involving risks to public health.

J Am Vet Med Assoc, 1990 Mar 15, 196(6), 877 - 80
Factors associated with circulation of pseudorabies virus within swine herds; Anderson PL et al.; Data were collected from 104 Minnesota swine farms quarantined for pseudorabies virus (PRV) infection . Each herd was serologically evaluated for the presence of antibodies to PRV in finishing pigs . Herd management practices, swine housing design, and disease profiles were described for each farm . Multiple logistic regression analysis was used to determine which factors were associated with circulation of PRV in the finishing pigs of farrow-to-finish farms . Sixty-seven (64%) of the herds had no serologic evidence of PRV circulation in the finishing section, whereas 37 herds (36%) contained at least one PRV seropositive finishing pig . The odds of a given finishing herd being seropositive for PRV were 2.85 times higher if the finishing pigs were housed in confinement (P = 0.01), 2 times higher if Actinobacillus (Haemophilus) pleuropneumoniae was a clinical problem in the herd (P = 0.03), 1.36 times less for each year that passed since the herd quarantine was issued (P = 0.01), 1.74 times higher if clinical signs of PRV were reported (P = 0.04), and 1.52 times higher if animal protein was included in at least one of the rations (P = 0.08).

J Biol Chem, 1990 Mar 5, 265(7), 3691 - 6
Purification and characterization of Haemophilus influenzae D-lactate dehydrogenase; Denicola-Seoane A et al.; Haemophilus influenzae D(-)-lactate dehydrogenase (D(-)-lactate:NAD oxidoreductase; EC 1.1.1.28) was purified to electrophoretic homogeneity using salt fractionation, hydrophobic and dye affinity chromatography . The enzyme was purified 2100-fold with a 14% recovery and a final specific activity of 300 units/mg protein . The enzyme was demonstrated to be a tetramer of Mr 135,000 . The enzyme catalyzed the reduction of pyruvate to give exclusively D(-)-lactate using NADH as coenzyme . The reaction catalyzed was essentially unidirectional, with the oxidation of D-lactate in the presence of NAD proceeding at less than 0.2% the rate of pyruvate reduction . Kinetic parameters for the reduction of pyruvate were determined for NADH and four structural analogs of the coenzyme . Coenzyme-competitive inhibition by adenosine derivatives indicated the presence of regions in the coenzyme binding site interacting with the adenosine and pyrophosphate moieties of the coenzyme . The purified enzyme was sensitive to oxidation and was effectively inactivated by sulfhydryl reagents . Conversion of D-lactate to pyruvate catalyzed by a membrane-bound D-lactate oxidase was demonstrated in cell-free extracts of H . influenzae.

Med J Aust, 1990 Mar 5, 152(5), 234 - 6, 238, 240
The epidemiology of invasive Haemophilus influenzae infections in children under five years of age in the Northern Territory: a three-year study; Hanna JN; A survey of all episodes of invasive Haemophilus influenzae infections that were diagnosed over a three-year period in children seen at the regional hospitals of the Northern Territory has found a significantly (P less than 0.001) higher incidence in children in Central Australia (the Alice Springs and Barkly regions, and the Anangu Pitjantjatjara Lands) than in the Top End (the Darwin, East Arnhem and Katherine regions), and a greater incidence in Aboriginal than in non-Aboriginal children . Identified risk factors for Aboriginal children were infancy (more than 70% of cases occurred before 12 months of age), sex (with a predominance in girls) and residence in Central Australia; the estimated annual incidence for Central Australian Aboriginal children was 991 cases per 100,000 children . There was a significant correlation (r = 0.62) between the total number of cases diagnosed each month in Central Australia and the mean monthly temperatures recorded in Alice Springs . Whereas virtually all cases of invasive H . influenzae infection in non-Aboriginal children were caused by type b strains, strains other than type b caused 15% of the cases in Aboriginal children . The possibilities for prevention by immunization are discussed.

Arch Otolaryngol Head Neck Surg, 1990 Mar, 116(3), 324 - 30
Analysis of immunocompetent cells in the middle ear mucosa; Ichimiya I et al.; A quantitative analysis of immunocompetent cells in the middle ear mucosa of mice was carried out by an indirect immunostaining method using various monoclonal antibodies . Mice bred in germ-free, specific pathogen-free, and conventional conditions were used to examine nonimmunized middle ear mucosa . Middle ear mucosae of otitis media-induced mice were also examined . In normal middle ear mucosa, mast cells were substantial, followed by Mac-1-positive cells and lymphocytes . Even though IgA-, IgM-, and Lyt-1-positive cells were seen in the mucosa of conventional mice, IgM-positive cells were seen only in mucosae of specific pathogen-free and germ-free mice . In otitis media-induced mice by inoculation with nontypable Haemophilus influenzae or lipopolysaccharide, Mac-1-positive cells were dominant . Although the numbers of IgM- and Lyt-1-positive cells increased markedly, the numbers of other lymphocyte subsets did not increase until 14 days after inoculation . These findings suggest that the middle ear is immunologically a potential organ as long as it is not exposed to antigenic stimulation . It is considered to be an immunoreactive site only after it has been activated with pathogens.

Eur J Clin Microbiol Infect Dis, 1990 Mar, 9(3), 201 - 5
In vitro synergism of rifampin-cephalosporin combinations against Haemophilus influenzae type b; Gordon RC et al.; The in vitro susceptibility of Haemophilus influenzae type b to rifampin, cefotaxime, ceftazidime, ceftriaxone and cefuroxime was examined at inocula of 10(5) and 10(7) CFU/ml . Time-kill curves were then obtained using antibiotic concentrations at one-half the MIC for each drug at the two inocula with combinations of rifampin plus each of the cephalosporins . There was a pronounced inoculum effect with all of the cephalosporins except for cefuroxime, but the MIC values were also higher for the latter drug . The rare failure of some cephalosporins to promptly sterilize the cerebrospinal fluid in meningitis should encourage investigation of the relationship between the inoculum effect, minimum bactericidal concentration and cerebrospinal fluid antibiotic levels in these clinical situations . A marked synergistic effect was noted for most of the isolates, and therefore, cephalosporin-rifampin combinations might show clinical utility.

Pediatr Infect Dis J, 1990 Mar, 9(3), 196 - 200
Septic shock in children: bacterial etiologies and temporal relationships; Jacobs RF et al.; In a retrospective analysis of 2110 admissions to the pediatric intensive care unit, 564 cases of septic shock were identified (26.7% of the total admissions) . Septic shock was defined in patients with: (1) clinical evidence of sepsis; (2) fever (greater than 38.3 degrees C) or hypothermia (less than 35.6 degrees C); (3) tachycardia; (4) tachypnea; and (5) inadequate organ perfusion . Inadequate perfusion was defined as hypotension or evidence of peripheral hypoperfusion (poor capillary refill or cyanosis with hypoxemia, oliguria, acidosis or altered mentation) . Inotropic support was required to maintain an adequate blood pressure and perfusion in 268 of 564 patients (47.5%) . Septic shock with confirmed bacterial infection occurred in 143 patients (143 of 564, 25.2%); these cases were caused by Haemophilus influenzae, type b (59 of 143, 41.3%), Neisseria meningitidis (26 of 143, 18.2%) and Streptococcus pneumoniae (16 of 143, 11.2%) . Eight of 564 (1.4%) cases of septic shock were not clinically apparent on initial evaluation and were diagnosed within 24 hours after admission to the hospital . We conclude that septic shock occurs more frequently in children than previously appreciated and may develop after admission to the hospital.

Pediatr Infect Dis J, 1990 Mar, 9(3), 181 - 6
Studies on Pneumococcus vaccine alone or mixed with DTP and on Pneumococcus type 6B and Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in two- to five-year-old children with sickle cell anemia; Sarnaik S et al.; Pneumococcus vaccine, injected alone or mixed with diphtheria-tetanus toxoid-pertussis, did not elicit significant concentrations of pneumococcus type 6 antibodies in 2- to 5-year-old sickle cell anemia patients (n = 22) . Reinjection 5 months later failed to elicit a booster response to pneumococcus type 6 . We then injected conjugates of pneumococcus type 6B and of Haemophilus influenzae type b (Hib), each bound to tetanus toxoid (TT), alternatively at monthly intervals into sickle cell anemia patients of the same age group (n = 25); most received 3 injections of each vaccine . Pneumococcus vaccine was administered to 19 patients and Hib to 1 at approximately 1 year of age . Blood samples were taken before each and approximately 6 months after the last injection . Infrequent and minimal local reactions and only 6 episodes of fever (3%) occurred after injection of the conjugates . Pneumococcus type 6B-TT elicited a rise in the geometric mean concentration of pneumococcus type 6 antibodies (Ab) from 104 ng of antibody nitrogen (AbN)/ml in preimmunization sera to 385 ng of AbN/ml after the first injection (P less than 0.01) . There were further increases after the 2 subsequent injections; 6 months after the third injection, the mean concentration was 940 ng of AbN/ml and 15 of 16 (94%) had greater than 300 ng of AbN/ml . Hib-TT elicited a 160-fold increase of Hib antibodies to a geometric mean concentration of 39.0 micrograms of Ab/ml after the first injection . These levels rose approximately 2-fold following 2 additional injections to 71.7 micrograms/ml and declined to 10.7 micrograms/ml at the 6-month sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

FEMS Microbiol Lett, 1990 Mar 1, 56(1-2), 41 - 4
Effect of iron limitation on protein composition and ultrastructure of Haemophilus ducreyi; Abeck D et al.; Protein profiles of whole cells of Haemophilus ducreyi grown in the presence or absence of the iron chelator desferal, were compared by polyacrylamide gel electrophoresis . Each of four strains produced novel proteins in the range 43-160 kDa when cultured under conditions of reduced iron availability . At some sub-inhibitory concentrations, desferal produced enhanced growth, possibly due to it functioning as an exogenous siderophore . Organisms grown under conditions of reduced iron availability ultrastructurally showed also large periplasmic spaces between cytoplasm and outer membrane.

Can J Public Health, 1990 Mar-Apr, 81(2), 152 - 5
Hib vaccine coverage in children attending day care/nursery school in East York; Whiting CM et al.; This survey assessed Haemophilus influenzae b vaccine coverage and factors affecting compliance in children at increased risk . A telephone survey was conducted of a random sample of 75 children, aged 24-60 months, attending licensed day care/nursery schools in East York . 96% of the sample was surveyed; only 51% were vaccinated . Older children were less likely to be immunized and there were more single-parent families among the non-vaccinated . The age, educational level and country of birth of the parents and the number of siblings were not associated with vaccination status . In 20% of the non-vaccinated group, concern about side effects was the main reason for non-compliance . For 91%, a factor of "moderate/very much concern" was the perceived unimportance of preventing Haemophilus influenzae b illness . Education for parents and physicians, special programs aimed at risk groups, and consideration of mandatory immunization against Haemophilus influenzae b in children attending day care/nursery schools are needed.

Thorax, 1990 Mar, 45(3), 187 - 9
Nosocomial lower respiratory tract infections in surgical wards; Kinnear WJ et al.; A six month prospective study of nosocomial lower respiratory tract infection was conducted in four general surgery wards and one urological surgery ward . Thirty eight cases were identified, representing 1% of the surgical admissions to these wards . Twenty eight of the infections followed abdominal surgery . Six patients died, five of whom had pre-existing cardiorespiratory disease . Potential pathogens were isolated in 21 patients, the commonest organisms being Streptococcus pneumoniae and Haemophilus influenzae.

J Clin Microbiol, 1990 Mar, 28(3), 430 - 4
Use of Haemophilus test medium for broth microdilution antimicrobial susceptibility testing of Streptococcus pneumoniae; Jorgensen JH et al.; A recently described medium (Haemophilus test medium {HTM}) for antimicrobial susceptibility testing of Haemophilus influenzae was evaluated in this study for broth microdilution testing of Streptococcus pneumoniae . A total of 137 clinical isolates was tested against 11 antimicrobial agents, using Mueller-Hinton broth supplemented with 3% lysed horse blood in parallel with HTM . Inocula of 5 X 10(5) CFU/ml and incubation for 20 to 24 h were used with both media . All isolates of S . pneumoniae produced acceptable growth in both media, and MICs determined in HTM agreed closely with those determined in lysed horse blood . Drugs which provided a MIC within 1 log2 concentration difference in both media included penicillin (100%), ampicillin (98.0%), amoxicillin-clavulanate (100%), ampicillin-sulbactam (100%), cephalexin (98.9%), cefaclor (96.8%), cefuroxime (99.0%), chloramphenicol (96.2%), tetracycline (96.2%), and erythromycin (100%) . HTM MICs with trimethoprim-sulfamethoxazole were 1 to 2 log2 concentration increments higher in 92.0% of isolates than MICs determined in lysed horse blood . Based on the results of this study, HTM appears to represent a promising alternative medium for broth microdilution susceptibility testing of S . pneumoniae.

J Infect, 1990 Mar, 20(2), 143 - 5
Haemophilus influenzae and H . parainfluenzae as urinary pathogens; Morgan MG et al.; Two cases are described, one of Haemophilus influenzae urinary infection in a female with no past history of urinary tract infection (UTI) and the other of Haemophilus parainfluenzae infection in a male with a renal calculus . Haemophilus spp . are rare urinary pathogens and these cases are even more unusual because H . influenzae UTI has almost always previously been found in either children or adult males, while H . parainfluenzae UTI has only been reported once before.

APMIS, 1990 Mar, 98(3), 269 - 75
Postantibiotic effect of the penem FCE 22101 against selected gram-positive and gram-negative bacteria in vitro and in vivo by the use of a tissue cage model in rabbits; Bergholm AM et al.; Isolates of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae were tested for their bactericidal activity and postantibiotic effect (PAE) with the new penem FCE 22101 . The tissue cage model in rabbits was used to study PAE in vivo . The bactericidal activity against all four species was shown to be in the range of 0.05-4.0 mg/l . A 99.9% killing effect at MBC concentrations was reached within 2 hours with S . pneumoniae and K . pneumoniae and within 6-8 hours with S . aureus and H . influenzae . After in vitro exposure by FCE 22101 a PAE in vitro and in vivo was obtained against S . aureus, S . pneumoniae and H . influenzae strains but no PAE could be demonstrated against K . pneumoniae . FCE 22101 showed a good bactericidal activity and PAE against the strains investigated, except for K . pneumoniae.

South Med J, 1990 Mar, 83(3), 348 - 9
Haemophilus influenzae meningitis in an adult with initially normal cerebrospinal fluid; Bamberger DM et al.; We have described an adult patient with signs and symptoms of bacterial meningitis who had an initially unremarkable cerebrospinal fluid examination, but then had development of fulminant meningitis over the next 48 hours . Bacterial meningitis with normal CSF values has been previously reported in children, immunocompromised hosts, and alcoholics, and in patients with fulminant infections due to Neisseria meningitidis . We recommend that all patients with signs and symptoms compatible with bacterial meningitis and with normal results of CSF examination have close follow-up clinically over the next 48 hours with consideration of repeating the lumbar puncture.

J Med Microbiol, 1990 Mar, 31(3), 163 - 8
Porphyrin ring source can alter the outer membrane protein profile of non-typable Haemophilus influenzae; MacIver I et al.; Porphyrin ring source appears to alter the outer membrane protein (OMP) profile of some, but not all, non-typable (NT) Haemophilus influenzae strains isolated from sputum . When haemin was replaced with protoporphyrin IX, 41% of strains examined produced increased amounts of a polypeptide of 84 Kda and new OMPs of either 120 or 150 Kda . Immunoblotting with paired patient's sera revealed that antibodies reactive with these proteins were present, demonstrating OMP antigenicity and expression in vivo and indicating that these isolates of NT H . influenzae may display an altered OMP phenotype when growing in the human lung.

J Infect Dis, 1990 Mar, 161(3), 512 - 7
Endogenous and exogenous reinfections by Haemophilus influenzae in patients with chronic obstructive pulmonary disease: the effect of antibiotic treatment on persistence; Groeneveld K et al.; To analyze whether exacerbations in chronic obstructive pulmonary disease (COPD) coincide with reinfection by Haemophilus influenzae, 16 COPD patients were studied longitudinally for 3 years . Exacerbations coincided with reinfection by H . influenzae, either endogenous, by a strain with a DNA fingerprint indistinguishable from the strain previously present but with another major outer membrane protein (MOMP) pattern (2 patients), or exogenous, by a strain with a different DNA fingerprint and MOMP pattern (3 patients) . The other patients, remaining in an infectious state without clear exacerbations for longer periods, were persistently infected by a particular H . influenzae strain (median persistence time, 5.5 months; range, 2-23 months) . Of 8 antibiotic-treated patients, 7 remained infected by H . influenzae with the same DNA fingerprint, although all strains were sensitive to the antibiotics prescribed . Results of the study suggested that exacerbations in COPD patients coincide with endogenous or exogenous reinfection by H . influenzae, persistently infected patients keep the same H . influenzae strain for longer periods, and antibiotic treatment was not effective in eradicating H . influenzae.

Arch Otolaryngol Head Neck Surg, 1990 Mar, 116(3), 335 - 7
Bacterial antigens and neutrophil granule proteins in middle ear effusions; Miller MB et al.; Otitis media with effusion is a significant cause of hearing loss in young children . We hypothesized that persistent bacterial antigens in middle ear effusions (MEEs) might act as chronic inflammatory stimuli causing release of neutrophil proteins . Concentrations of neutrophil lactoferrin and a 37-kd cationic bactericidal protein (CAP 37) were measured in 47 MEEs collected from 27 children at the time of tympanostomy tube placement . Antigens of Streptococcus pneumoniae were detected by latex particle agglutination and those of Haemophilus influenzae by dot-blot assay . Bacterial antigens were detectable in 24 (51%) of MEEs: S pneumoniae in 10 (21%), H influenzae in 12 (26%), and both antigens in 2 (4%) . Concentrations of lactoferrin and CAP 37 in H influenzae antigen-positive MEEs were significantly higher than in either S pneumoniae antigen-positive or antigen-negative MEEs . We conclude that H influenzae antigen causes a greater middle-ear inflammatory response, as judged by neutrophil products, than does S pneumoniae antigen.

Am J Dis Child, 1990 Mar, 144(3), 292 - 5
Protective efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid-conjugate vaccine; Nelson WL et al.; We estimated the relative protective efficacy of Haemophilus influenzae type b polysaccharide (PRP) vaccine and PRP-diphtheria toxoid-conjugate (PRP-D) vaccine using data from reports of cases of invasive Haemophilus disease occurring in vaccinated children submitted to the Food and Drug Administration, Rockville, Md, and Washington University, St Louis, Mo . During the first 13 months following licensure of each of the vaccines, there were 127 cases reported in recipients of PRP vaccine vs 17 cases in recipients of PRP-D vaccine . The total number of reported cases for each vaccine is not necessarily comparable, since the extent of vaccine use in the population and the extent of reporting of cases may have been different during the two periods . However, the proportion of reported cases occurring equal to or 14 days or more after vaccination (a period considered sufficient to develop immunity) was significantly greater for PRP vaccine (106 {83%} of 127 cases) compared with PRP-D vaccine (7 {41%} of 17 cases) . Based on the ratio of late-onset to early-onset cases observed for PRP vaccine, we would have expected 50 late-onset cases after PRP-D vaccination . Since only 7 late-onset PRP-D vaccine failures were reported (86% fewer than expected), the data suggest that PRP-D vaccine was more effective in preventing disease 14 days or more after vaccination than was PRP vaccine.

Pediatrics, 1990 Mar, 85(3), 331 - 7
Safety and immunologic response to Haemophilus influenzae type b oligosaccharide-CRM197 conjugate vaccine in 1- to 6-month-old infants; Madore DV et al.; A Haemophilus influenzae type b oligosaccharide-CRM197 conjugate (HbOC) vaccine was evaluated for safety and immunogenicity in 432 infants 1 to 6 months of age . In a multicenter study involving 10 sites in six states, infants were vaccinated with three 10-micrograms doses of HbOC at 2-month intervals . Side effects associated with vaccination were mild, transient, and occurred in fewer than 2% of the subjects . More than 90% of infants of all ages responded after two doses, and more than 98% had anti-H influenzae type b capsular polysaccharide (HbPs) antibody levels greater than or equal to 1 microgram/mL after three doses . One month after the third vaccination, the geometric mean anti-HbPs antibody levels were 16.84, 26.23, and 29.11 in infants initially vaccinated at 1 to 2, 3 to 4, and 5 to 6 months of age, respectively . A long-term antibody response was observed; more than 80% of these infants had anti-HbPs levels greater than or equal to 1 microgram/mL at 2 years of age . The HbOC generated an immune response characteristic of a protein antigen; IgG anti-HbPs antibodies of IgG1 subclass predominated and the response could be boosted . The immune sera killed H influenzae type b when evaluated in an in vitro bactericidal assay . The data indicate that HbOC safely primed and boosted the immune system of young infants, providing long-lasting protective levels of anti-HbPs antibodies.

Pediatrics, 1990 Mar, 85(3), 288 - 93
Persistence of antibody and booster responses to reimmunization with Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children initially immunized at 15 to 24 months of age; Berkowitz CD et al.; To evaluate the persistence of antibody after Haemophilus influenzae type b polysaccharide vaccine (PRP) and H influenzae type b polysaccharide diphtheria toxoid conjugate vaccine (PRP-D), a group of 141 infants initially immunized between 15 and 24 months of age were studied 1 year later . One month after immunization with PRP, the man anti-PRP antibody level was 0.27 microgram/mL and 1 year later was 0.29 microgram/mL (not significant) . In the group immunized with PRP-D, the levels were 1.34 micrograms/mL and 1.20 micrograms/mL (not significant), respectively . To evaluate immunogenicity and safety of a booster immunization 1 year after initial vaccination, subjects were randomly assigned to receive saline, PRP, or PRP-D . In addition, 73 age-matched previously unimmunized subjects were vaccinated with PRP or PRP-D . In all groups, adverse reactions were minor and resolved by 48 hours . Subjects receiving booster immunization with PRP or PRP-D had significantly greater antibody responses than children of the same age receiving their first dose of vaccine . The highest antibody levels were achieved in children initially immunized with PRP-D, regardless of whether the booster vaccine was PRP (112.8 micrograms/mL) or PRP-D (122.0 micrograms/mL) (not significant) . Antibody levels after booster vaccine were significantly lower in those initially given PRP compared with those initially given PRP-D but significantly higher than in age-matched previously unimmunized control subjects (PRP booster 3.16 micrograms/mL vs control of 0.62 microgram/mL {P less than .05}; PRP-D booster 12.31 micrograms/mL vs control 2.31 micrograms/mL {P less than .01}).

Arch Dis Child, 1990 Mar, 65(3), 255 - 8
Haemophilus infection in cystic fibrosis; Rayner RJ et al.; Twenty seven patients with cystic fibrosis under the age of 12 years and 27 matched patients with asthma were followed up in a prospective study for one year . The isolation rate of non-capsulated strains of Haemophilus influenzae from cough swabs and sputum specimens taken at routine clinic visits every two months was significantly greater in cystic fibrosis than in asthma . Haemophilus para-influenzae was equally common in both groups . During exacerbations the isolation rate of H influenzae in cystic fibrosis was significantly greater than at other times, whereas in asthma there was no significant difference . The distribution of biotypes of H influenzae and H parainfluenzae was similar in the two groups . In cystic fibrosis, biotype I was associated with exacerbations . Biotype V was more common than in previous studies, but was not associated with exacerbations.

Infection, 1990 Mar-Apr, 18(2), 78 - 82
Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: results of a Swiss multicenter study . Part II: Bacteriological results; Hohl P et al.; The in vitro activity of ceftriaxone, ampicillin and chloramphenicol was studied at a reference laboratory against the isolates of the first 33 patients enrolled in a pediatric Swiss Multicenter Meningitis Study . The predictive value of the MIC data of 31 of the strains was further corroborated by two sets of bacterial killing curves in broth supplemented with 2 g/l of albumin . Ceftriaxone had the lowest geometric mean MIC values against all groups of isolates except for ampicillin against Streptococcus agalactiae . The bactericidal activity of ceftriaxone and that of ampicillin, alone and in combination with chloramphenicol, was compared at six times the respective MICs and at pharmacologically readily achievable concentrations in cerebrospinal fluid . The bactericidal power of ceftriaxone at six times the MIC was as good or better than that of ampicillin alone or in combination against Neisseria meningitidis and Streptococcus pneumoniae despite the very low drug concentrations of ceftriaxone compared to that of the competitors; and it was barely lower at six times the MIC and at 1 mg/l (a level that is readily surpassed in CSF at the 24 h trough level after a single daily dose of ceftriaxone of 100 mg/kg (neonates 50 mg/kg) than that of ampicillin and chloramphenicol at much higher concentrations against Haemophilus influenzae type b.

Infection, 1990 Mar-Apr, 18(2), 70 - 7
Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: results of a Swiss multicenter study . Part I: Clinical results; Martin E et al.; In a prospective Swiss multicenter study, 119 children (aged three weeks to 15.5 years) with acute bacterial meningitis were treated with single daily doses of ceftriaxone (100 mg/kg on days one and two and 60 mg/kg thereafter) . All patients were randomly assigned to either short course (four, six, seven days) or full course (eight, 12, 14 days) therapy depending on whether they had contracted meningococcal, Haemophilus influenzae type b or pneumococcal meningitis . Bacteriological cure was obtained in 92 children who fully completed the study and in all the 20 culture-positive of the 27 children secondarily excluded from the study for failure to meet all bacteriological and initial safety criteria for continuation in protocol (secondary exclusions) . Complete clinical recovery was noted in 105 of 119 patients (88%) and was as frequent in the short course (91%) as in the full course (89%), and as in the secondary exclusion (81%) group . All patients survived . At follow-up examination three to six months after hospital discharge only seven infants and seven children (11.8%), mostly those with poor presentation on admission (p = 0.0012), showed residual neurological sequelae . Side effects of antibiotic therapy were minor but more frequent, albeit not statistically significant (p = 0.065), in children receiving the full course therapy . The results of this study suggest that short course treatment of acute bacterial meningitis in children with single daily ceftriaxone monotherapy is as efficacious as full course therapy and at least as well tolerated.

Acta Otolaryngol, 1990 Mar-Apr, 109(3-4), 314 - 9
Colonization by Haemophilus influenzae and group A streptococci in recurrent acute tonsillitis and in tonsillar hypertrophy; Stjernquist-Desatnik A et al.; One hundred patients subjected to tonsillectomy because of recurrent acute tonsillitis or tonsillar hypertrophy were evaluated bacteriologically both with ordinary throat culturing and cultures from tonsillar cores . In 26% of the patients H . influenzae was isolated and in 20% beta-haemolytic group A streptococci . Growth of B . catarrhalis was obtained in 10% and group C-, group G streptococci or pneumococci in less than 5% each . None of the group A streptococcal strains proved tolerant to penicillin . A much higher isolation rate of H . influenzae was found in cultures obtained from tonsillar core tissue (23%) than from ordinary throat cultures (2%) . This was also the fact, though to a lower extent, regarding group A streptococci . H . influenzae and group A streptococci were isolated as often in patients with tonsillar hypertrophy as in patients suffering from recurrent acute tonsillitis, suggesting a role of these bacteria in both conditions.

J Med Microbiol, 1990 Mar, 31(3), 219 - 24
The production and characterisation of rabbit antiserum and murine monoclonal antibodies to Haemophilus ducreyi; Finn GY et al.; Rabbit antiserum and murine monoclonal antibodies were raised against a strain of Haemophilus ducreyi . The antiserum gave high immunofluorescence titres and strong dot blot reactions with all H . ducreyi strains tested and the only cross reaction was with Bordetella pertussis . Three monoclonal antibodies, all of isotype IgG2a, also gave high immunofluorescence titres with H . ducreyi but did not cross react with any other species tested . Immunoblotting showed the monoclonal antibodies to react with a single polypeptide band of mol . wt 29,000 in the outer-membrane fraction of H . ducreyi . These antibodies have potential for use as diagnostic reagents and for investigating the pathogenicity of H . ducreyi.

J Gen Microbiol, 1990 Mar, 136 ( Pt 3), 425 - 30
Studies of NAD kinase and NMN:ATP adenylyltransferase in Haemophilus influenzae; Denicola-Seoane A et al.; Previous studies of Haemophilus influenzae documented the importance of several pyridine nucleotide-dependent enzymes in processing extracellular NAD and NMN to satisfy the V-factor growth requirement of the organism . The substrate specificities of two of these enzymes . NMN:ATP adenylyltransferase and NAD kinase, were investigated following partial purification . The ability of the transferase to utilize 3-acetylpyridine mononucleotide and 3-aminopyridine mononucleotide as substrates for the synthesis of the corresponding dinucleotides was demonstrated . The NAD kinase was observed to accept 3-acetylpyridine adenine dinucleotide as a substrate but failed to utilize 3-aminopyridine adenine dinucleotide . The mononucleotides of 3-acetylpyridine and 3-aminopyridine were shown to be as effective as the corresponding dinucleotides in the support of growth and inhibition of growth of H . influenzae, respectively . Inhibition of growth of H . influenzae by submicromolar 3-aminopyridine adenine dinucleotide was shown to occur because 3-aminopyridine mononucleotide was produced from it in reactions catalysed by the H . influenzae periplasmic nucleotide pyrophosphatase . The presence of an additional important pyridine nucleotide-dependent enzyme, NMN glycohydrolase, is also reported.

Antimicrob Agents Chemother, 1990 Mar, 34(3), 476 - 8
Characterization of the Tet M determinants in urogenital and respiratory bacteria; Roberts MC; Tetracycline-resistant Fusobacterium nucleatum, Haemophilus ducreyi, Mycoplasma hominis, Peptostreptococcus spp., Ureaplasma urealyticum, and Veillonella parvula had DNA sequences which showed homology throughout the length of the Tet M transposon, Tn916 . In contrast, Gardnerella vaginalis, commensal Neisseria spp., and the 25.2-megadalton plasmid family lacked the complete transposon.

Cesk Epidemiol Mikrobiol Imunol, 1990 Mar, 39(2), 106 - 12
{Isolation of Haemophilus aphrophilus from a blood culture}; Aldova E et al.; The authors describe the method of isolation and identification and differential diagnosis from a morphologically, cultivation and biochemically close species H . (A.) actinomycemcomitans . They discuss the problem of the taxonomic classification of the two species.

J Int Med Res, 1990 Mar-Apr, 18(2), 171 - 6
Clinical efficacy and tolerance of two new macrolides, clarithromycin and josamycin, in the treatment of patients with acute exacerbations of chronic bronchitis; Fraschini F; The efficacy and safety of oral 500 mg clarithromycin given twice daily and 500 mg josamycin given three times daily were compared for up to 14 days in the treatment of 103 out-patients with acute exacerbations of chronic bronchitis in an open, randomized study . The predominant pathogens isolated were Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus . Clinical cures were experienced by 85% of the clarithromycin-treated patients, with an additional 10% showing improvement . In josamycin-treated patients, 76% of the patients experienced clinical cures and an additional 19% showed improvement . Eradication of the causative pathogen occurred in approximately 95% of the patients in both treatment groups . Adverse events, which all involved the gastro-intestinal tract and were mild, transient and probably related to therapy, were experienced by 5.8% and 7.8%, respectively, of the clarithromycin- and josamycin-treated patients . It is concluded that clarithromycin given twice daily is as effective as josamycin given three times daily.

J Antibiot (Tokyo), 1990 Mar, 43(3), 295 - 305
Chemical modification of erythromycins . III . In vitro and in vivo antibacterial activities of new semisynthetic 6-O-methylerythromycins A, TE-031 (clarithromycin) and TE-032; Morimoto S et al.; The in vitro and in vivo antibacterial activities of 6-O-methylerythromycin A (TE-031, A-56268, or clarithromycin) and 6,11-di-O-methylerythromycin A (TE-032) have been compared with those of erythromycin A (EM) and josamycin (JM) . TE-031 and TE-032, having the same antibacterial spectra as EM, are active against aerobic Gram-positive bacteria, some Gram-negative bacteria, anaerobic bacteria, L-form bacteria and Mycoplasma pneumoniae . The activity of TE-031 against clinical isolates is equal to or two times more potent than that of EM, whereas TE-032 is slightly less active than EM . The activities of TE-031 and TE-032 are pH dependent (more active at pH 8 than at 5) and are increased by adding serum to medium . TE-031 and TE-032 show dose-related bactericidal activities against Haemophilus influenzae . The therapeutic efficacies of TE-031 and TE-032 against systemic and subcutaneous infections provoked by Gram-positive bacteria in mice are 4- to 35-fold superior to those of EM and JM . TE-031 and TE-032 have demonstrated higher and longer-lasting plasma levels than EM when administered orally to mice, rats or dogs.

J Bacteriol, 1990 Mar, 172(3), 1374 - 9
Capsulation in distantly related strains of Haemophilus influenzae type b: genetic drift and gene transfer at the capsulation locus; Kroll JS et al.; Among natural populations of capsulate Haemophilus influenzae, clones of strains with type b capsular polysaccharide are found in each of two widely separated phylogenetic divisions . The chromosomal capsulation locus found in strains from either division has a three-segment organization, with serotype-specific DNA nested between elements common to all serotypes, but pairwise comparison of the segments between the divisions suggests that they have distinct phylogenetic histories . Genes clustered in one of the non-serotype-specific segments appear to have diverged from an ancestral element, reflected in 12% nucleotide sequence divergence in one homologous pair . In contrast, genes conferring the capacity to produce type-specific polysaccharide exhibit no such divergence, and we speculate that these have been subject more recently to horizontal transfer within the bacterial population . Clinically important capsulate gram-negative bacteria share a common organization of their capsulation loci, arguing convergence on a successful arrangement of genes . In H . influenzae this appears to have allowed the occasional exchange of serotype-specific capsulation genes between strains, a event of potential clinical importance in this major bacterial pathogen.

Nippon Shishubyo Gakkai Kaishi, 1990 Mar, 32(1), 275 - 88
{The clinical and etiological study on juvenile periodontal disease}; Matsue M et al.; Seven juvenile periodontally diseased patients were evaluated for clinical, microbiologic and local or systemic host factors . Three patients showed the localized from of periodontitis clinically and radiographically and by deep periodontal pockets associated with the molars and incisors . Four were in the generalized froms, in which in most cases all teeth were affected . The results in both diseased froms on the predominant cultivable subgingival microflora, the composition of which was not different from that in adult periodontitis, consisted of significantly increased proportions of Gram-negative anaerobic rods, Bacteroides sp . and B . gingivalis, Haemophilus sp . and H . actinomycetemcomitans were detected in 1/3 of the localized and 2/4 of the generalized periodontitis . They were of no value in distinguishing activity that enhanced disease in the generalized from . Elevated serum IgG responses were noted with B . gingivalis . No markedly functional abnormalities of neutrophils from peripheral blood have been demonstrated, however it might function with systemic factors, like an insulin-dependent diabetes . Morphologic characteristics of the oral and periodontal tissue in localized periodontitis were that the pattern of destruction was confined to specific teeth groups characterized by extensive the bucco-lingual width ratio of the dental crown to alveolar bone width . These observations indicate that the generalized form of juvenile periodontitis lesions were associated not only with the presence of subgingival bacteria, but also with conditions such as local morphologic and systemic or constitutional factors, individual variation in relation to destructive and protective aspects of the defense mechanisms.

J Gen Microbiol, 1990 Mar, 136 ( Pt 3), 507 - 13
Multivariate analysis of quantitative chemical and enzymic characterization data in classification of Actinobacillus, Haemophilus and Pasteurella spp; Brondz I et al.; Chemotaxonomic data for strains of Actinobacillus, Haemophilus and Pasteurella spp . were analysed using three multivariate statistical strategies: principal components, partial least squares discriminant, and soft independent modelling of class analogy . The species comprised Actinobacillus actinomycetemcomitans . Haemophilus aphrophilus, H . paraphrophilus, H . influenzae, Pasteurella multocida, P . haemolytica and P . ureae . Strains were characterized by cell sugar and fatty acid composition, lysis kinetics during EDTA and EDTA plus lysozyme treatment, and methylene blue reduction . In total 23 quantitative variables were compiled from chemotaxonomic analyses of 25 strains . A . actinomycetemcomitans and H . aphrophilus formed distinct classes which differed from those of H . paraphrophilus, H . influenzae and Pasteurella spp . All characterization variables, except those describing fatty acid content, contributed significantly to inter-species discrimination.

Clin Ther, 1990 Mar-Apr, 12(2), 105 - 17
Bacterial isolates and cigarette smoking in patients with chronic bronchitis: results from an Italian multicenter survey; Cazzola M et al.; Patients who were cigarette smokers suffering exacerbations of chronic bronchitis were examined in eight outpatient clinics in five regions of Italy, three from the South (Campania, 82 patients; Sicily, 82 patients; and Puglia, 29 patients) and two from North (Lombardy, 33 patients; and Liguria, 50 patients) . Haemophilus influenzae was the most frequently isolated bacterium in the patients' sputum (in 30% of the total group), followed by Streptococcus pneumoniae (in 20%), Staphylococcus aureus (in 25%), and Branhamella catarrhalis (in 7%) . H . influenzae was the most common bacterium in the South (in 37%) and S aureus in the North (in 13%) . Smoking index scores (number of cigarettes smoked daily x years of smoking) were 827 in patients in whom H influenzae was isolated; 691 in patients with S aureus; 599 in patients with S pneumoniae; 542 in patients with B catarrhalis; and 446 in patients in whom no isolates were found . Pulmonary function was most severely decreased in patients positive for H influenzae and S aureus . The results indicate an association between heavy cigarette smoking and lower respiratory tract infections that is influenced by regional differences.

J Clin Microbiol, 1990 Mar, 28(3), 422 - 5
Sialidase (neuraminidase) activity among gram-negative anaerobic and capnophilic bacteria; Moncla BJ et al.; A filter paper spot test with 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid as a substrate was used to study the prevalence of sialidase activity among gram-negative anaerobic and capnophilic bacteria . A total of 567 isolates representing four genera of obligate anaerobes and four genera of capnophilic organisms was tested . Sialidase activity was detected in 94% of 66 isolates from the Bacteroides fragilis group, 98% of 66 B . bivius isolates, and all isolates of the following species (number of isolates follows species name): B . capillosus, 4; B . levii, 2; B . denticola, 22; B . loescheii, 23; B . melaninogenicus, 32; B . forsythus, 44; and B . buccalis, 2 . However, sialidase activity was detected in only 29% of 7 B . buccae isolates, 79% of 14 B . disiens isolates, and 55% of 11 B . oralis isolates . Sialidase activity was not detected among any of 13 isolates of B . gracilis, 12 isolates of B . ureolyticus, 61 isolates of B . intermedius, or 26 isolates of B . corporis . Porphyromonas (Bacteroides) asaccharolytica (20 isolates) and P . endodontalis (8 isolates) did not demonstrate sialidase activity, while 25 isolates of P . gingivalis were sialidase positive . Sialidase activity was found in 10 (100%) of 10 isolates of Capnocytophaga ochracea of C . sputigena but not in any of 4 C . gingivalis isolates . Other gram-negative anaerobic or capnophilic bacteria, including the following, were negative for sialidase activity: Fusobacterium nucleatum, 39 isolates; Wolinella recta, 19 isolates; Eikenella corrodens, 17 isolates; Haemophilus aphrophilus, 10 isolates; and Actinobacillus actinomycetemcomitans, 10 isolates . These data demonstrate sialidase activity in several species of the genera Bacteroides and Porphyromonas and suggest that this characteristic may be useful for identification.

J Infect Dis, 1990 Mar, 161(3), 574 - 7
Distribution and excretion of capsular antigen after immunization with Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; Sood SK et al.; The occurrence of Haemophilus influenzae type b capsular polysaccharide antigenemia and antigenuria following immunization was studied in 48 healthy 2-month-old infants . Each received a conjugate vaccine consisting of H . influenzae type b capsular polysaccharide covalently linked to Neisseria meningitidis serotype b outer membrane protein at 2 and 4 months of age . Infants were alternated at enrollment for collection of blood and urine after either the first or second dose . Specimens were obtained "early" (2-3 days) after immunization and "late" (7 days) after immunization and assayed for antigen . Antigen was detected in the serum of 3 (6%) of 48 infants, uniformly in the "early" specimen obtained after the first dose of vaccine . Antigenuria occurred in 37 (80%) of 46 infants; for greater than or equal to 7 days in 12 (26%) . Antigenuria was frequent after administration of the vaccine but antigenemia was not . These data should be considered in the evaluation of an infant with suspected H . influenzae type b invasive disease.

Ann Trop Paediatr, 1990 Mar, 10(1), 89 - 98
Pyogenic meningitis in hospitalized children in Kelantan, Malaysia; Choo KE et al.; A 2.5-year retrospective study of pyogenic meningitis in hospitalized children in Kelantan was carried out with regard to aetiology, clinical features, investigation, treatment and outcome . There were 58 children with 43 cases (74.1%) occurring below the age of 1 year . Frequent presenting symptoms included fever (98.3%), fits (77.6%), anorexia (39.7%), vomiting (34.5%) and drowsiness (12.1%) . On admission, 37 (63.7%) had neck stiffness, 10 (17.2%) had Kernig's sign and 32 (55.2%) had coma . CSF cultures were positive for Haemophilus influenzae in 29 (50%), Streptococcus pneumonia in 13 (22.4%) and Neisseria meningitidis in 3 (5.2%) . The antibiotic sensitivity profiles showed that the three main organisms were 100% sensitive to Chloramphenicol, Streptococcus pneumoniae was 100% sensitive to penicillin, Neisseria meningitidis was 100% sensitive to penicillin and ampicillin, and Haemophilus influenzae was 90% sensitive to penicillin and ampicillin . The total hospital mortality was 18.9% . All but two of the eleven deaths occurred in children younger than 1 year . Nineteen of the 35 (54.3%) survivors attended for at least one follow-up after discharge from hospital . Of these 19 children, 47.4% had neurological sequelae.

J Clin Microbiol, 1990 Mar, 28(3), 535 - 9
Cross-reactions between Actinobacillus (Haemophilus) pleuropneumoniae strains of serotypes 1 and 9; Mittal KR; Actinobacillus pleuropneumoniae strains of serotypes 1 and 9 were studied for their serological properties by means of agglutination, coagglutination (CoA), indirect hemagglutination (IHA), Co-IHA, ring precipitation (RP), and immunodiffusion (ID) tests . Particulate and soluble antigens of unheated and heat-treated bacterial cells were used in various serological tests . Agglutination, CoA, and RP tests demonstrated common antigens between strains of serotypes 1 and 9 . Quantitative estimation of serotype-specific antigenic activity by CoA, RP, and ID tests proved useful in differentiating strains of serotypes 1 and 9 . IHA and Co-IHA tests using sheep erythrocytes sensitized with unheated or heat-treated whole-cell saline extract and the ID test using boiled whole-cell saline extract as antigen distinguished the strains of serotypes 1 and 9 . In studies of absorption of rabbit antisera with heterologous whole-cell antigens there was no absorption of antibodies in tube agglutination and IHA tests, suggesting that serotype 1 and 9 strains belong to two distinct serogroups . It appears that the cross-reactivity between serotype 1 and 9 strains could be due to common epitopes associated with cell wall antigens.

J Immunol, 1990 Feb 15, 144(4), 1221 - 6
Human polysaccharide-specific B cells are responsive to pokeweed mitogen and IL-6; Ambrosino DM et al.; The responsiveness of polysaccharide-specific B cells to PWM was examined in vitro . Spleen cells from six patients immunized with Haemophilus influenzae type b-diphtheria toxoid, pneumococcal and meningococcal vaccines were T cell-depleted and separated by Percoll density gradient centrifugation . In each B cell fraction, spontaneous antibody production was demonstrated to capsular polysaccharides as well as diphtheria toxoid . The peak of spontaneous antibody production was demonstrated to be five to seven days after immunization . When T cells and PWM were added, the total Ig secretion increased in all B cell fractions . PWM also enhanced IgG antibody directed to each of three polysaccharide Ag measured . This enhancement was most noticeable for nonresting B cells . The PWM effect was not confined to IgG, as IgM and IgA to Neisseria meningitidis type C were measured and also enhanced . The kinetics of the PWM response demonstrated the most IgG antibody to polysaccharide Ag from spleens immunized five to seven days before splenectomy . When the patients were immunized either 2 days or 4 mo before splenectomy, no spontaneous IgG antibody to polysaccharides was detected although PWM induced small amounts of antibody . Finally, anti-IL-6 antibody blocked PWM-induced total and polysaccharide-specific antibody production . We conclude that human polysaccharide-specific B cells are responsive to PWM and IL-6 . We suggest that polysaccharide B cells are not truly "T cell-independent" and may respond to T cell lymphokines and thus are similar to protein-specific B cells.

J Infect Dis, 1990 Feb, 161(2), 274 - 80
Pilus- and non-pilus-mediated interactions of Haemophilus influenzae type b with human erythrocytes and human nasopharyngeal mucosa; Farley MM et al.; The role of pili of Haemophilus influenzae type b (Hib) in binding to human erythrocytes and in colonization and invasion of human nasopharyngeal (NP) organ cultures has been evaluated . Hib strains 1009 and 1007, NP and cerebrospinal fluid isolates from the same child with Hib meningitis, were studied . Strain 1009 was piliated (P+), produced pilin of approximately 24 kDa, and was hemadsorption-positive (HA+); strain 1007 was nonpiliated (P-), did not produce pilin, and was hemadsorption-negative (HA-) . The rate of transition from one hemadsorption phenotype to the other in broth cultures and NP organ culture supernatants was 3 x 10(-4) per bacterium per generation for HA+ to HA- and 7 x 10(-4) per bacterium per generation for HA- to HA+ . Growth in human NP organ culture supernatants of the P+HA+ strain was greater than that of the P-HA- strain at 6 and 12 h after infection . No difference was noted when the strains were grown in nutrient broth . Strain 1009 (P+HA+) attached in large clusters to cellular debris and nonciliated cells, a phenomenon never noted with strain 1007 (P-HA-) . NP organ cultures infected with strain 1007 showed greater mucosal invasion than those infected with the 1009 strain . While P+HA+ and P-HA- Hib both attached to NP mucosa, P+HA+ strains may have a selective advantage in mucosal colonization but P-HA- strains may be more invasive.

Laryngoscope, 1990 Feb, 100(2 Pt 1), 149 - 51
Central nervous system complications associated with acute otitis media in children; Friedman EM et al.; The purpose of this article is to review a subset of pediatric patients with otitis media occurring simultaneously with meningitis and other central nervous system diseases . Of the 92 cases reviewed, 61.3% involved patients under 12 months of age . Meningitis associated with otitis media involved 91% of the patients; the remainder had nonmeningitic central involvement . The most striking finding was the high incidence of Haemophilus influenza type-B, a relatively uncommon pathogen of the middle ear . This finding highlights the need to select antibiotic coverage to adequately treat Haemophilus influenza type-B.

J Paediatr Child Health, 1990 Feb, 26(1), 46 - 9
Antibody response of 18 month old children 1 month and 18 months following Haemophilus influenzae type b vaccine administered singly or with DTP vaccine; Clements DA et al.; Seventy-six children (aged 17-19 months) received 10 micrograms of Haemophilus influenzae type b polyribosyl-ribitol phosphate (PRP) vaccine, diluted with either phosphate-buffered saline (PBS) or diphtheria-tetanus-pertussis (DTP) vaccine, in a single-blind randomized trial . There were few side effects when PRP was administered alone . Before vaccination 37 of 76 children (49%) had non-protective antibody levels (less than 0.15 micrograms/mL); 26 of these 37 (70%) achieved antibody levels of greater than 0.15 micrograms/mL 1 month after vaccination . Before vaccination 16 of 76 (21%) had antibody levels of greater than 1.0 micrograms/mL; 1 month after vaccination 39 of 76 children (51%) achieved levels of greater than 1.0 micrograms/mL . Of 12 infants who had antibody levels less than 0.15 micrograms/mL 1 month after immunization, 10 had protective levels 18 months later . Administration of PRP mixed with DTP did not affect antibody response to PRP . The potential use and limitations of PRP vaccine are discussed.

Antimicrob Agents Chemother, 1990 Feb, 34(2), 363 - 5
Identification of a group of Haemophilus influenzae penicillin-binding proteins that may have complementary physiological roles; Malouin F et al.; {35S}penicillin bound to different Haemophilus influenzae proteins in assays performed at 20, 37, or 42 degrees C . Penicillin-binding proteins 3a, 3b, 4, and 4' formed a group characterized by their affinity for moxalactam, cefotaxime, and piperacillin . Penicillin-binding protein 4' showed specific properties that may reflect its complementary role in septation.

Aust N Z J Med, 1990 Feb, 20(1), 35 - 8
Bacterial colonisation of the respiratory tract in chronic bronchitis; Butt HL et al.; One hundred and nine subjects with chronic bronchitis were studied prior to winter and without clinical infection, to determine baseline patterns of bacterial colonisation . Qualitative analysis of cultures of oropharyngeal swabs showed little difference from age matched normal controls (17) except for growth of small numbers of Gram negative coliforms in the chronic bronchitic group . Quantitation of bacteria colonising the oropharynx showed small numbers (mean of 10(5) cfu/ml), with no particular bacteria dominating . Haemophilus influenzae was present in 7.3% of throat swabs from chronic bronchitic patients, but the organism was always less than 10% of the total count . Quantitation of bacteria in sputum showed significantly higher numbers (mean 10(7) cfu/ml) . H . influenzae was detected in 25.7% of available specimens, and when present constituted greater than 90% of the total count . Biotyping of H . influenzae isolates demonstrated a separate colonisation of the upper and lower respiratory tracts.

Arch Dis Child, 1990 Feb, 65(2), 175 - 7
Bacterial reservoirs in cystic fibrosis; Taylor CJ et al.; To establish whether colonisation of the upper respiratory tract or bacterial contamination of inhaler devices or solutions predisposes to colonisation of the lower respiratory tract in patients with cystic fibrosis, bacterial isolates from groups of children who were positive (n = 13) or negative (n = 18) for Pseudomonas aeruginosa were studied . Cultures of swabs from inhaler devices, toothbrushes, and upper airways were compared with cough swabs or sputum cultures . No pathogens were obtained from inhaler equipment administering unit dose medications . Upper airway carriage of Staphylococcus aureus and Haemophilus influenzae was identified in both groups but correlated poorly with sputum isolates . P . aeruginosa was found only in the upper respiratory tract of children with established colonisation of the lower airways . No P aeruginosa isolates were obtained from the upper airways of the group with negative sputum, including one patient who became colonised by P aeruginosa during the study . Our results did not support the suggestion that colonisation of the upper respiratory tract by P aeruginosa predisposes to colonisation of the lower airways . Failure to isolate pathogenic organisms consistently from the upper airways in patients with positive sputum argues against a local epithelial factor predisposing to bacterial colonisation.

J Clin Microbiol, 1990 Feb, 28(2), 319 - 23
Species-specific oligodeoxynucleotide probes for the identification of periodontal bacteria; Dix K et al.; Oligodeoxynucleotide probes were developed for identification of the periodontal bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, B . intermedius types I and II, B . forsythus, Eikenella corrodens, Fusobacterium nucleatum, Haemophilus aphrophilus, Streptococcus intermedius, and Wolinella recta . Probes were designed by sequencing the 16S rRNA for each bacterium, identifying hypervariable regions, and chemically synthesizing species-specific probes . These probes were specific when tested against a panel of nucleic acids from closely related bacteria.

Br J Ophthalmol, 1990 Feb, 74(2), 118 - 20
Infective conjunctivitis and corneal scarring in three brothers with sex linked hypogammaglobulinaemia (Bruton's disease); Hansel TT et al.; The ocular findings in three brothers with Bruton's disease are reported . All three boys had purulent conjunctivitis, but the two older brothers also developed marked corneal scarring with visual impairment . Haemophilus influenzae was cultured from conjunctival swabs; it was resistant to neomycin but sensitive to chloramphenicol . Tear analysis showed that the three subjects had normal levels of lysozyme but no detectable IgA.

J Trop Med Hyg, 1990 Feb, 93(1), 7 - 11
Childhood bacterial meningitis in Kuwait; Zaki M et al.; A total of 110 cases of bacterial meningitis were studied over a 7-year period . The attack rate was 3.2/100,000 overall and 13/100,000 in children under 12 years . Haemophilus influenzae was the most common pathogen (44.3%), followed by Streptococcus pneumoniae (20.9%) and Neisseria meningitidis (12.7%) . The mean patient age was 2.7 years, but 44/49 cases of H . influenzae meningitis were in children under 2 years, an attack rate of 31/100,000 . The mortality was 22.4% for neonates and 6.5% for other children, and was associated with coma at presentation and unusual microorganisms . Neurological sequelae were detected in 19% of surviving children.

APMIS, 1990 Feb, 98(2), 122 - 4
Mixed bacterial meningitis in an adult caused by Haemophilus influenzae and Streptococcus pneumoniae . A case report; Jensen A et al.; A case of mixed bacterial meningitis with Haemophilus influenzae and Streptococcus pneumoniae is reported in a 26-year-old woman without demonstrable predisposing conditions, who recovered after treatment with ampicillin, without sequelae.

Am J Vet Res, 1990 Feb, 51(2), 227 - 31
Effects of Mycoplasma hyopneumoniae and Actinobacillus (Haemophilus) pleuropneumoniae infections on alveolar macrophage functions in swine; Caruso JP et al.; Alveolar macrophages were collected at necropsy from pigs inoculated with Mycoplasma hyopneumoniae or Actinobacillus pleuropneumoniae or both and were tested for phagocytic capabilities, using in vitro techniques . Macrophages from noninoculated littermates were used as controls . Alveolar macrophages from pigs inoculated with either M hyopneumoniae or A pleuropneumoniae had significantly (P less than 0.05 to P less than 0.0025) higher phagocytic capacity than that of noninoculated controls . Macrophages from A pleuropneumoniae-inoculated pigs were comparatively more stimulated than were those from M hyopneumoniae-inoculated pigs . Pigs inoculated with M hyopneumoniae and then challenge-exposed with A pleuropneumoniae 2 and 4 weeks later had greatly reduced phagocytosis . Infection with M hyopneumoniae or A pleuropneumoniae caused stimulation of alveolar macrophage functions, and M hyopneumoniae infections may have suppressed phagocytic responses when pigs were challenge-exposed with a secondary pathogen (A pleuropneumoniae) . This potential suppression may represent a prediposition of the host by M hyopneumoniae to secondary bacterial infections.

Infect Immun, 1990 Feb, 58(2), 358 - 65
Efficacy of a cell extract from Actinobacillus (Haemophilus) pleuropneumoniae serotype 1 against disease in swine; Fedorka-Cray PJ et al.; We partially characterized a cell extract (CE) from Actinobacillus pleuropneumoniae serotype 1 and used the CE to test the efficacy of secreted proteins against disease . Secreted products from 4-h culture supernatants were precipitated with 20% polyethylene glycol . Analysis of the CE indicated the presence of protein, endotoxin, and carbohydrate . Hemolytic activity to bovine erythrocytes and cytotoxic activity to porcine mononuclear leukocytes was also demonstrated . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the CE from a 4-h culture showed a major band at 110 kilodaltons (kDa), while a CE of a 26-h culture indicated the presence of a number of additional proteins, including the 110-kDa protein . The 110-kDa protein was also identified as a glycoprotein by periodic acid-Schiff and silver staining . A single band precipitated against convalescent-phase pig antiserum when the polyethylene glycol precipitate was used in an Ouchterlony plate . Vaccination with CE conferred greater protection against challenge with the homologous serotype than either a commercial bacterin or an outer membrane protein vaccine . Hemolysin-neutralizing titers were higher both pre- and postchallenge in the group vaccinated with the CE compared with in all other groups . We believe that this demonstrates the importance of secreted factors in protection against disease and suggests that the 110-kDa protein is an important immunogen.

Am J Public Health, 1990 Feb, 80(2), 215 - 6
The incidence of Haemophilus influenzae meningitis in a midwestern metropolitan county; Rice RB et al.; The incidence of H . influenzae meningitis in children under five years of age was monitored during the years 1983-87 by a retrospective study of records from all hospitals serving a metropolitan county in Kansas . The mean annual incidence rate for the five years studied was 26.0 per 100,000 . This compares with a mean of 56.0 per 100,000 measured in the same county during 1979-82.

Arq Bras Cardiol, 1990 Feb, 54(2), 101 - 4
{Mitral valve prolapse in infective endocarditis . Incidence and characteristics}; Rossi EG et al.; PURPOSE valve prolapse (MVP) cases, complicated with infective endocarditis (IE), seen at a cardiologic reference hospital . METHODS--The MVP cases were diagnosed within a series of 276 cases of IE without previous cardiac surgery with clinical-echocardiographic criteria . We emphasised in our study; a) incidence; b) age and sex distribution; c) risk factors for IE; d) clinical-bacteriological data; e) echocardiographic features; f) therapeutic aspects; f) evolution and complications . RESULTS--a) We diagnosed 40 (14.4%) cases of MVP; b) mean age of 40.6 years, with 29 men (72.5%); c) dental procedures without prophylactic antibiotic-therapy in seven patients (17.5%), mitral regurgitation in 33 (82.5%), mitral valve redundancy in six (15%); d) fever was found in all patients (100%), cachexia was diagnosed in eight (20%), polyarthritis in six (15%) and congestive heart failure in six (15%) . A systolic murmur of mitral regurgitation was found in all the patients and a nonejective click was encountered in four (10%), a Streptococcus was cultivated in 30 (75%), Staphylococcus in three (7.5%) Haemophilus sp in three (7.5%) Peptostreptococcus products in one (2.5%) and negative in three (7.5%) patients; e) echocardiographic signs of vegetation in 23 (57.5%), mitral regurgitation in 33 (82.5%), rupture of mitral chordae in 11 (27.5%) and mitral redundance in six (15.2%); f) 37 (92.5%) patients were medically treated and three (7.5%) required surgery; g) we registered in the hospital evolution: stroke in 10 (25%) and noncerebral mycotic aneurysm in 2 (5%) cases, two patients died (5%), one due to a hemorrhagic complication after surgery of bioprosthesis implantation and another of rupture of a cerebral mycotic aneurysm . CONCLUSION--The MVP was frequent in the population of patients with IE with of patients with mitral regurgitation, and male with mean age greater than the other cases . We observed low incidence of surgical need (7.5%) and lethal outcome (5%) but frequent (25%) neurological complications.

Jpn J Antibiot, 1990 Feb, 43(2), 326 - 36
{Clinical evaluation of cefteram pivoxil in respiratory tract infections}; Miyazaki RM et al.; The usefulness of cefteram pivoxil (CFTM-PI) was evaluated in 99 cases with respiratory tract infections: 32 cases with acute bronchitis, 51 cases with infectious exacerbations of chronic respiratory diseases and 16 cases with pneumonia . 1 . The clinical efficacies included marked improvement in 27 cases, improvement in 51 cases, moderate improvement in 9 cases, no change in 10 cases and deterioration in 2 cases . The improvement rate was 78.8% . 2 . Overall effects were excellent in 12 cases, good in 9 cases and fair in 5 cases . There was no case in which efficacy was not observed and the efficacy rate was 80.8% . 3 . Bacteriological effects were classified according to the causative organisms . Eradication rate was 80.8% (21 of 26 strains), indicating an excellent antibacterial action of CFTM-PI . In particular, MICs of cefteram were below 0.05 microgram/ml against all 10 strains of Haemophilus influenzae regardless of beta-lactamase production even with an inoculum of 10(8) or 10(6) cells/ml . 4 . Side effects rarely occurred and included a slight gastrointestinal irritation in 4 of 99 cases (4%) . Two cases which had abnormal elevations of GOT and GPT had abnormal values prior to administration of CFTM-PI . The elevations were slight and it was possible to continue administration . The GOT and GPT values were improved after the end of administration . The above results indicate the usefulness of CFTM-PI in acute respiratory infections and infectious exacerbation of chronic respiratory diseases.

Jpn J Antibiot, 1990 Feb, 43(2), 239 - 56
{Clinical evaluation of sulbactam/cefoperazone in lower respiratory tract infections}; Ishibashi T et al.; Clinical evaluation, safety and kinetics in serum of sulbactam/cefoperazone (SBT/CPZ) in patients with lower respiratory tract infections have been studied in a multicenter trial participated by 28 institutions in Kyushu area during a period of 13 months from March 1987 to March 1988 . 1 . Mean peak serum levels of SBT and CPZ in 35 patients up to 4 hours after intravenous infusion of 2 g of SBT/CPZ were 38.2 +/- 17.3 micrograms/ml for SBT and 104.3 +/- 31.4 micrograms/ml for CPZ . Serum half-lives of SBT and CPZ were 0.76 hour and 1.53 hours, respectively . These results were in similar ranges to those reported elsewhere for SBT/CPZ . 2 . Serum half-lives of SBT and CPZ after intravenous infusion of 2 g of SBT/CPZ were not significantly prolonged in patients with moderate liver or kidney dysfunctions . 3 . Clinical efficacy rates of SBT/CPZ in 217 patients were 93.1% (81/87) for pneumonia, 93.3% (14/15) for lung abscess, 78.9% (15/19) for acute exacerbation of chronic bronchitis, 57.1% (4/7) for diffuse panbronchiolitis, 72.4% (21/29), 74.4% (32/43) and 100% (9/9) for infections concurrent to bronchiectasis, chronic respiratory disease and pulmonary emphysema, respectively . Those were 50% (1/2) for bronchitis associated with lung cancer and 66.7% (4/6) for empyema . The overall efficacy rate was 83.4% (181/217) . 4 . Clinical efficacy rate of SBT/CPZ for pneumonia in patients with underlying diseases such as lung cancer, pulmonary tuberculosis and pneumoconiosis, etc, was 85.3% (29/34) and was not significantly different from the efficacy rate of 98.1% (52/53) in patients without these underlying diseases . 5 . Of 30 patients who failed to respond of previous antibiotic treatments, 21 were effectively treated by SBT/CPZ . 6 . Bacteriological eradication rates against Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae were 42.9% (9/21), 87.5% (14/16) and 100% (5/5), respectively . The overall eradication rate in all cases including polymicrobial infections was 72.8% (67/92) . 7 . The high levels of peak serum concentration of CPZ, and the difference between serum levels of SBT and of CPZ seemed to contribute to the high clinical efficacy . 8 . Adverse reactions occurred in 2.8% (6/217) of the patients, and consisted primarily of rash and diarrhea . Laboratory abnormalities were observed in 8 patients during the study . These were elevations of S-GOT and S-GPT, and eosinophilia . 9 . SBT/CPZ is a very useful drug in the treatment of lower respiratory tract infections as it has become available just in time when increase in resistant organisms to beta-lactams is notable.

Rev Med Chil, 1990 Feb, 118(2), 146 - 52
{Haemophilus influenzae carriers among child care personnel: its prevalence and the efficacy of enoxacin in its elimination}; Prado V et al.; In a previous study we observed that 6% of adult and 18% of children contacts of H . influenzae infected patients became carriers of the bacillus . We studied 1296 adults involved in children care, 398 from day care centers and 898 from hospitals in Santiago . A pharyngeal sample was cultured in chocolate agar plus bacitracin (300 mg/ml) and incubated at 37 degrees C in a 5-10% CO2 atmosphere for 18-24 h . Isolates of H influenzae were biotypified and serogrouped according to international recommendations . We observed that 2.4% of subjects were H influenzae carriers . Thirty carriers were treated with 2 doses of enoxacin, 440 mg . All became free of H influenzae at a 30-day follow-up.

J Chemother, 1990 Feb, 2(1), 26 - 30
In-vitro activity of ampicillin/sulbactam and other antibiotics against clinical isolates of Haemophilus sp . and Branhamella catarrhalis; Stefani S et al.; The ampicillin/sulbactam combination is one of several such drug combinations of a beta-lactam and suicide inhibitor having a wide spectrum of activity . These characteristics induced us to evaluate the in vitro activity of this combination towards 54 strains of Haemophilus sp . (38 beta-lactamase producers) and 20 strains of Branhamella catarrhalis (16 beta-lactamase producers) . All strains were isolated from sputum, sinusal aspiration and tympanocentesis . In the case of Haemophilus sp beta-lactamase producers, minimal inhibitory concentrations of ampicillin were reduced 8 times by the use of the inhibitor; good results were also obtained for B . catarrhalis . Haemophilus influenzae, B . catarrhalis together with Streptococcus pneumoniae are recognized as the major pathogens involved in upper respiratory tract infections . The increasing frequency of beta-lactamase producing strains has impaired the use of aminopenicillins . The combination of an inhibitor and beta-lactam restore the activity of the latter, suggesting that this combination can serve as first choice in therapy.

Eur J Clin Microbiol Infect Dis, 1990 Feb, 9(2), 138 - 41
Frequent isolation of capnophilic bacteria in aspirate from Bartholin's gland abscesses and cysts; Quentin R et al.; Aspirate samples were obtained from 73 patients undergoing surgery for a Bartholin's gland abscess or cyst . Capnophilic bacteria were isolated from 22% of cases, in contrast to previous reports of sporadic isolation . The three Streptococcus pneumoniae isolates were serotype 3 or 4 . The eight Haemophilus influenzae isolates could not be serotyped; six of them were biotype II but the electrophoretic band patterns of their outer membrane proteins were heterogeneous, indicating that non-serotypable strains from the same anatomical site may not be related . Four Neisseria gonorrhoeae isolates and one strain of Neisseria subflava were recovered . The role of capnophilic bacteria in the pathogenesis of infections of the Bartholin's gland remains to be clarified.

Infect Immun, 1990 Feb, 58(2), 320 - 31
Localization of the cleavage site specificity determinant of Haemophilus influenzae immunoglobulin A1 protease genes; Grundy FJ et al.; Immunoglobulin A1 (IgA1) proteases are produced by a number of different species of bacteria which cause infection at human mucosal surfaces . The sole substrate of these proteases is human IgA1 . Cleavage is within the hinge region of IgA1, although there is variability in the exact peptide bond within the hinge region that is cut by a particular protease . The cleavage site of the Haemophilus influenzae type 1 protease is located four amino acids from the cleavage site of the type 2 enzyme . In this study, the region of the H . influenzae IgA1 protease gene (iga) that determines the cleavage site specificity was localized through the comparison of the type 1 and type 2 genes and the construction and analysis of type 1-type 2 hybrid genes . The hybrid genes were generated by in vivo and in vitro techniques which facilitated the selection and screening of randomly generated hybrids . The cleavage site determinant was found to be within a 370-base-pair region near the amino-terminal coding region, in one of two large areas of nonhomology between the two types of H . influenzae iga genes . DNA sequence analysis of the cleavage site determinant and surrounding regions did not reveal a simple mechanism whereby one enzyme type could be converted to the other type . Comparison of the type 2 gonococcal IgA1 protease gene to the two Haemophilus genes revealed a significant amount of homology around the cleavage site determinant, with the two type 2 genes showing greater homology.

Oral Microbiol Immunol, 1990 Feb, 5(1), 24 - 8
An in vitro method to study the adherence of bacteria to saliva-treated tooth enamel sections; Sweet SP et al.; An in vitro bacterial adherence assay which employed human tooth enamel sections precoated with saliva and an epifluorescent staining technique with acridine orange was developed . The assay was used to study the adherence properties of fresh and type strains of the following oral bacterial species: Bacteroides gingivalis, Bacteroides intermedius, Capnocytophaga species, Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Peptostreptococcus species, Veillonella species, Actinomyces israelii, Streptococcus salivarius and Streptococcus sanguis . Approximately half of the bacteria tested adhered well to enamel, including the fresh isolates of B . gingivalis, B . intermedius, Veillonella species and S . sanguis . Adherence did not correlate in all cases with the known distribution of these species in vivo . Three-quarters of the fresh strains adhered better than the type strains of the same species . The assay method is an alternative to the widely used hydroxyapatite bead assay.

J Protein Chem, 1990 Feb, 9(1), 45 - 52
The complete primary structure of pilin from Haemophilus influenzae type b strain Eagan; Armes LG et al.; Adherence of Haemophilus influenzae type b (Hib) to human oropharyngeal cells is mediated by pili which are proteinaceous filaments that extend outward from the bacterial cell surface . Pili from Hib strain Eagan were purified, and the primary structure of the major subunit, pilin, was determined . Sequencing of overlapping peptides showed the mature protein to be comprised of 196 amino acids and to have an Mr of 21,152 . The amino terminal sequence was found to be homologous with the sequence previously reported for Hib strain M43 and also to have significant homology to pilins of other gram-negative pathogenic bacteria . Furthermore, Hib pilin had two cysteinyl residues in the amino terminal portion of the protein which were separated by 40 residues (positions 21 and 61); a motif found in other bacterial pilins . The data show that Hib pilin has structural features common to other bacterial pilins.

Mol Microbiol, 1990 Feb, 4(2), 221 - 30
Molecular analysis of the Haemophilus influenzae type b pilin gene; Langermann S et al.; A Haemophilus influenzae DNA library was prepared in the vector lambda EMBL3, and recombinant phage were screened for the pilin gene (pil) using a synthetic oligonucleotide . Southern blot analysis of the positive clones revealed a 2.5kb PstI/PvuI fragment that hybridized with the oligonucleotide probe . This fragment was subcloned into pBR322 and sequenced . The nucleotide sequence disclosed an open reading frame of 653 bases . The deduced amino acid sequence corresponded with the known amino acid sequence of the purified pilin protein . Primer extension analysis using total RNA from piliated H . influenzae cells delineated a start site for the gene, -10 and -35 promoter regions, and a ribosome-binding site . No transcripts were seen with the RNA derived from a non-piliated strain . Southern blots of DNA from a number of H . influenzae strains revealed homology with the pil structural gene . DNA from a non-piliated strain of H . influenzae also hybridized with the pil probe . Transcriptional and translational studies were performed in Escherichia coli with plasmids containing: (i) the pil gene on the 2.5 kb PstI/PvuI fragment, (ii) the pil gene fused to the phoA gene, and (iii) the pil gene present on a 12.2 kb insert containing extensive H . influenzae DNA flanking the pil gene . The results suggest that the H . influenzae pil gene is expressed in Escherichia coli, but from a promoter other than the one used in H . influenzae.

Nippon Juigaku Zasshi, 1990 Feb, 52(1), 1 - 9
Drug-susceptibility and isolation of a plasmid in Haemophilus (Actinobacillus) pleuropneumoniae; Ishii H et al.; We isolated 56 Haemophilus (Actinobacillus) pleuropneumoniae strains from the pneumonic porcine lung tissues and tested them for antimicrobial susceptibility . Two drug-resistant strains were obtained . One, named KH-265, was resistant to streptomycin (SM) and sulfonamide (SA), and the other, named KH-195, was resistant to tetracycline (TC) . The minimum inhibitory concentrations (MICs) of drugs for resistant strains were 100 micrograms/mliters for SM, 3200 micrograms/mliters for SA, and 12.5 micrograms/mliters for TC . KH-265 possessed a 8.3Kb nonconjugative plasmid, pMS260, encoding SM and SA resistance, which was transformable to E . coli strains . pMS260 belonged to none of 14 incompatibility groups including Inc . P and Inc . Q, so far tested . It was mobilizable to various causative strains for respiratory infections, Pseudomonas aeruginosa, Bordetella bronchiseptica, Pasteurella multocida and Haemophilus pleuropneumoniae, by RP4 (Inc . P) plasmid.

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