Scand J Infect Dis, 1988, 20(5), 511 - 6 Bacteriology of maxillary sinusitis in relation to character of inflammation and prior treatment; Berg O et al.; By antral aspiration, 200 sinus secretions were obtained from the same number of adult patients with maxillary sinusitis . The bacteriological findings were related to the character of the secretions as well as to the duration of symptoms, previous antibacterial treatment and possible dental genesis . Pathogens were isolated in 87% of 54 patients with untreated acute sinus empyema, Streptococcus pneumoniae being the most prevalent (57%) . In 47 cases of treatment failure Haemophilus influenzae predominated and was found in 60% of the purulent secretions . In all, 11% of the 47 cases showed growth of beta-lactamase-producing H . influenzae, corresponding to 18% of all H . influenzae in this group . Staphylococcus aureus and anaerobic bacteria were infrequent findings except in purulent sinus secretion from patients with a long history . In contrast to patients with sinus empyema, no pathogens were found in the majority of 37 patients with non-purulent sinusitis. Drugs Exp Clin Res, 1988, 14(6), 411 - 7 Bacteriological and clinical evaluation of cefotetan in the treatment of severe infections in hospitalized patients; Romanelli G et al.; The authors studied 302 hospitalized patients, 164 males and 138 females aged 15-88 years (average 66 years), with severe infections . Cefotetan was administered to 278 of them at the dose of 1 or 2 g, b.i.d . or a single daily dose i.m . Other patients {24} were treated with a continuous intravenous infusion of cefotetan (3 g daily in 5% dextrose) . Of these patients 121 were treated for urinary tract infections (UTI); 114 for respiratory tract infections (RTI); 41 for liver biliary duct infections (BDI); 17 for skin or skin structure infections (SKI); 6 for fever of unknown origin and 3 for sepsis . The following Gram-positive organisms {156} were isolated: Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus group D; and the following Gram-negative organisms {122}: Escherichia coli, Proteus vulgaris, Proteus mirabilis, Serratia spp., Klebsiella spp., Haemophilus influenzae and Pseudomonas aeruginosa . The overall eradication rate for Gram-positive organisms was 74% and for Gram-negative organisms it was 88% . The clinical response was satisfactory in 87.7% of patients (specifically, cefotetan was effective in 90% of UTI, 84.2% of RTI, 97.5% of BDI and 82.3% of SKI) . The drug was well tolerated and side-effects (such as skin rash, diarrhoea, purpura and pain at the site of injection) occurred in only 4% of patients treated with cefotetan . In conclusion, cefotetan appears to be safe and highly effective for the treatment of severe infections in hospitalized patients. Microbios, 1988, 54(220-221), 181 - 5 Effect of capsular material from Haemophilus actinomycetemcomitans on bone collagen synthesis in vitro; Wilson M et al.; Capsular material was extracted from Haemophilus actinomycetemcomitans, an organism associated with localised juvenile periodontitis, and examined for its effect on the in vitro synthesis of collagen and DNA in mouse calvaria . The material was found to cause a significant inhibition of both collagen and DNA synthesis at concentrations as low as 10 ng ml-1 . The ability of capsular material to inhibit bone formation, together with its previously described bone resorbing activity, suggests that it may contribute to the rapid alveolar bone loss which is characteristic of localised juvenile periodontitis. APMIS Suppl, 1988, 3, 13 - 6 Evaluation of a latex kit reagent for the detection and identification of pneumococci; West PW et al.; The ability of a commercial latex kit to detect pneumococcal antigen in 50 CSF samples, 150 ear swabs and 80 sputum samples was investigated . Results were compared with microscopic and culture findings . 18/19 culture-positive specimens were latex-positive . 7 latex-positive specimens yielded organisms other than S . pneumoniae which agglutinated the latex, 4 Klebsiella spp, 2 Staphylococcus aureus and 1 Haemophilus influenzae . For 11 other specimens latex agglutination was positive and culture negative . S . pneumoniae was recovered from the blood of 1 of these patients and, in 2 further cases, microscopy showed poorly stained organisms which had some resemblance to S . pneumoniae . For 10 different strains of S . pneumoniae suspensions containing between 10(4) and 10(7) organisms per ml were required to agglutinate the latex. Br J Dis Chest, 1988 Jan, 82(1), 56 - 63 Pulmonary epithelial permeability in bronchiectasis; Chan TB et al.; We measured pulmonary epithelial permeability in 17 non-smoking patients with generalized bronchiectasis, of whom six had cystic fibrosis, by determining the half-time clearance from lung to blood (T1/2LB) of inhaled 99mTc-labelled diethylene triamine pentaacetate . Their age range was 15-79 years and the range of their FEV1 measurements was 20-87% of the predicted normal . Sputum obtained by prestudy chest physiotherapy revealed significant colonies of Pseudomonas aeruginosa in six, Haemophilus influenzae in three, Staphylococcus aureus in three and Pasteurella mitocida in one patient, while in the remainder there was normal flora only . Lung clearance was significantly faster in the 13 culture-positive patients (mean T1/2LB = 28 minutes) compared with the four culture-negative patients (mean T1/2LB = 54 minutes) . There was no correlation between T1/2LB and prestudy FEV1 . The study was repeated in six patients following a course of antibiotics . In two patients only was the sputum cleared of organisms and in those the lung permeability decreased significantly . There was no change in lung permeability in the four patients in whom it was impossible to eradicate the sputum organisms . Thus, in our patients with generalized bronchiectasis, lung permeability was increased only in those with both purulent sputum and significant colonization of the respiratory tract by bacterial pathogens . However, this increase in lung permeability was not associated with worse lung function. Auris Nasus Larynx, 1988, 15(2), 105 - 11 The antibiotic susceptibilities and beta-lactamase production of clinical isolated Branhamella catarrhalis from acute otitis media in children; Suzuki K et al.; Branhamella catarrhalis has been misconsidered as a normal resident in human respiratory tract for a long time . However, many authors recently have reported its pathogenecity and isolated it from the otolaryngological region . In our study, this organism can be isolated from the ear and nasal discharge in the child with acute otitis media by the rate of 7.5% and 21.4% respectively . Out of this 107 isolated strains, 97 strains (90.7%) were found to be beta-lactamase producing organisms . The MIC measurement of penicillins and cephems (except CEX) for inhibition of all these strains in our study is 6.25 micrograms/ml or less and because of the unreliability of the ABPC's susceptibility test by disk method, it is necessary to check the beta-lactamase production in each strain . Becoming of the high emergence rate of beta-lactamase producing strains, B . catarrhalis should be considered to be as important pathogen as Streptococcus pneumoniae and Haemophilus influenzae in upper respiratory tract infections in children. J Emerg Med, 1988 Jan-Feb, 6(1), 33 - 5 Effects of causative organism and presence or absence of meningitis on white blood cell counts in children with bacteremia; Kline MW et al.; The records of 182 children with bacteremia due to Streptococcus pneumoniae, Haemophilus influenzae type b, or Neisseria meningitidis were reviewed to determine which variables other than the presence or absence of bacteremia might affect patients' white blood cell (WBC) counts . There were no significant or consistent effects of age, sex, race, or duration of illness on WBC counts . Significantly lower mean WBC counts were noted for patients with, versus those without, meningitis and patients with H influenzae type b bacteremia versus those with S pneumoniae bacteremia . As a screening test for bacteremia, the WBC count is less useful in children with either meningitis or infection caused by H influenzae type b than in children with nonmeningeal infections caused by S pneumoniae. Scand J Infect Dis Suppl, 1988, 57, 41 - 9 The role of beta-lactamase-producing bacteria in respiratory tract infections; Brook I; Staphylococcus aureus, Haemophilus influenzae, Bacteroides sp . (Bacteroides melaninogenicus, Bacteroides oralis, and Bacteroides fragilis), peptostreptococci and fusobacterium sp . are important pathogens in respiratory tract infections (RTI) . These organisms are often recovered mixed with other aerobic, facultative and anaerobic bacteria . A recent increase in numbers of bet-lactamase producing strains of anaerobic gram-negative bacteria in RTI has been associated with increased failure rates of penicillins in eradication of these infections . These infections include chronic otitis media, chronic sinusitis and mastoiditis, chronic recurrent tonsillitis and lung abscesses . The indirect pathogenicity of these organisms is apparent through their ability not only to survive penicillin therapy but also to protect penicillin susceptible pathogens from that drug . These direct and indirect virulence characteristics of anaerobic bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections. J Electron Microsc Tech, 1988 Jan, 8(1), 105 - 13 Mycobacterium avium-intracellulare complex infections in the acquired immunodeficiency syndrome; Perfect JR; This review examines an important bacterial infection in acquired immunodeficiency syndrome (AIDS) . Despite occasional infections with bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, Salmonella, and Nocardia in patients with AIDS, the primary problems of AIDS and invading bacterial infections center around mycobacteriosis . A unique feature of AIDS has been the common identification of disseminated infections with Mycobacterium avium-intracellulare . The following discussion examines our present understanding of this group of organisms and how they interact with the compromised host. Chemotherapy, 1988, 34 Suppl 1, 47 - 52 Ceftriaxone in the treatment of bacterial meningitis in adults; Zavala I et al.; Twenty-six adults with acute bacterial meningitis were enrolled in an open randomized comparative study . The organisms isolated from CSF were Streptococcus pneumoniae, Staphylococcus epidermidis, Haemophilus influenzae, Escherichia coli and Salmonella typhi . 13 patients (group A) were treated once daily with intravenous ceftriaxone (Rocephin) . The 13 patients in group B received ampicillin or ampicillin plus chloramphenicol in 4 doses/day . The mean duration of therapy in groups A and B was 9.9 and 12.3 days, respectively . This difference in the duration of therapy was statistically significant . All patients from group A showed clinical improvement and all were bacteriologically cured . In group B only 12 patients were clinically and bacteriologically cured; 1 patient had to be withdrawn from the therapy because CSF culture remained positive after 48 h of therapy . Ceftriaxone was well tolerated in all patients; ampicillin or ampicillin plus chloramphenicol were associated with diarrhea and skin rash in 6 patients. Chemotherapy, 1988, 34 Suppl 1, 3 - 15 Bactericidal effect of ceftriaxone versus imipenem plus cilastatin in bronchial secretion; Fraschini F et al.; The bactericidal quotient (BQ) assessed in the site of infection represents an essential parameter for evaluating the real bactericidal potency of an antibiotic in vivo . The assessment and knowledge of BQ values allow us to set up a more accurate and appropriate antibacterial therapy . The two drugs--ceftriaxone (Rocephin) and imipenem plus cilastatin (Tienam)--that have been taken into consideration in this study, having a similar antibacterial spectrum though with different kinetics, may have the same BQ values in bronchial secretion versus Haemophilus influenzae, Klebsiella pneumoniae and Streptococcus pneumoniae, when administered at different dosages, i.e . ceftriaxone 1 g (i.v.) every 24 h, imipenem 0.5 g (i.v.) every 8 h. Scand J Infect Dis, 1988, 20(5), 517 - 24 Comparison of amoxycillin/clavulanate with amoxycillin in children and adults with chronic obstructive pulmonary disease and infection with Haemophilus influenzae; Jensen T et al.; 71 children and adults (median age 7 years) with chronic obstructive pulmonary disease in which ampicillin-sensitive Haemophilus influenzae were isolated from lower airway secretions were included in a single-blind study comparing amoxycillin/clavulanate and amoxycillin alone . The dosage of amoxycillin was 50 mg/kg/day given together with probenecid and divided in 3 doses . Duration of treatment was 14 days . Clinical and bacteriological examinations were performed at study entry and again immediately after the treatment period . A late bacteriological follow-up 1.5 months after entry was performed . 65 patients were eligible for analysis of clinical outcome, and no difference between the groups was found . Side-effects were mild at a frequency of 3% for either preparation . In terms of eradication of the initially isolated H . influenzae amoxycillin/clavulanate tended to be better than amoxycillin, although the difference was not significant (70% and 57%, respectively) . In a subset of 33 patients with polymicrobial flora amoxycillin/clavulanate was significantly more effective than amoxycillin . However, amoxycillin/clavulanate did not significantly reduce the emergency of beta-lactamase producing H . influenzae during treatment, and thus offers no advantage over amoxycillin in patients with amoxycillin-sensitive H . influenzae . The combination should be reserved to patients with either polymicrobial flora or ampicillin-resistant H . influenzae. Microbios, 1988, 55(222), 25 - 31 Periodontopathic micro-organisms in the rice rat (Oryzomys palustris); Shklair IL et al.; The rice rat spontaneously develops periodontal disease, and this process can be accelerated if the animal is placed on a high sucrose diet . As the aetiological agent(s) is unknown, this study was undertaken to determine the micro-organisms associated with bone loss . Animals at weaning were placed on either a high sucrose diet or on regular rat chow and were sampled periodically for a variety of micro-organisms . Bacteroides spp., spirochetes, and Actinobacillus actinomycetemcomitans were not isolated from any animals, but fusiform-like organisms and Capnocytophaga spp . were isolated occasionally . An unidentified organism which had characteristics of both A . actinomycetemcomitans and Haemophilus aphrophilus was isolated from all animals at every sampling . Whether this organism is the primary aetiological agent of periodontal disease in the rice rat remains to be determined . Over the 12 week experimental period the animals on the high sucrose diet had significantly more exposed root surface than animals on regular rat chow. Padiatr Padol, 1988, 23(3), 257 - 72 {Clinico-immunologic aspects of IgG subclass deficiency}; Eibl MM; Serum IgG contains 4 subclasses, IgG1 (60-66%), IgG2 (20-30%), IgG3 (less than or equal to 5%) and IgG4 . Individual subclasses vary with respect to their physicochemical and biological properties . IgG subclass concentrations in serum are age dependent . IgG1 and IgG3 reach near to adult levels around the age of 3, IgG2 and IgG4 after the age of 6 . Antibodies of certain specificities generally belong to a certain isotype (subclass) due to the isotype restriction . Patients with subclass deficiencies often suffer from recurrent infections . Those with IgG2 deficiency (often occurring with IgA and IgG4 deficiency) develop recurrent infection of the upper and lower respiratory tract often caused by pyogenic microorganisms (Haemophilus, Pneumococcus) . Since early initiation of IVIG substitution therapy has a beneficial effect on long term prognosis the importance of early diagnosis is apparent. Doc Ophthalmol, 1988 Jan-Feb, 68(1-2), 135 - 44 The French Egyptian campaign and its effects on ophthalmology; Wagemans M et al.; Almost all soldiers of the armies involved in the Egyptian campaign fell victim to what was later called the ophthalmia militaris which we now know to be caused by Haemophilus aegyptius, N . gonorrhoea and possibly to some extent by Chlamydia trachomatis but more likely by the adenoviruses . Because of the enormous incidence of ocular infection and the controversy generated by speculation on the nature of the disease--English surgeons considered this ophthalmia to be of a contagious nature, whereas the French surgeons violently opposed this view-, the interest in diseases of the eye increased, which eventually resulted in the acceptance of ophthalmology as a separate branch of medicine. Clin Ther, 1988, 10(5), 568 - 73 Community-acquired pneumonia: etiology, diagnosis, and treatment; Johnson RH; Pneumonia is an important cause of morbidity and mortality . A variety of conditions that damage the airways and weaken host defense mechanisms increase the susceptibility of the individual to bacterial colonization of the pulmonary tree . Because the clinician frequently cannot determine the etiologic agent, pneumonia is often treated empirically . Cefonicid, a long-acting cephalosporin, is a useful and cost-effective antibiotic that is active against many of the common pathogens that cause community-acquired pneumonia, such as Streptococcus pneumoniae and Haemophilus influenzae . It is also active against less common community-acquired pathogens, such as Klebsiella pneumoniae, Escherichia coli, and some anaerobic mouth flora . Erythromycin is useful when Mycoplasma or Legionella species are suspected . Cefonicid's demonstrated safety and efficacy, its low cost, and its long half-life, permitting once-daily dosing, make this antibiotic an ideal parenteral choice for empiric therapy of community-acquired pneumonia. Monatsschr Kinderheilkd, 1988 Jan, 136(1), 31 - 7 {IgG subclass deficiency in childhood . Changes in the antigen specific immune response and significance of low IgG4 level}; Bartmann P et al.; The definition of IgG subclass deficiency and the correlations between low IgG subclass serum concentrations and high incidence of infections in certain patients are still obscure . Therefore 260 children from 6 months to 18 years with severe recurrent infections or a known immunodeficiency were screened for IgG subclass deficiency . Nine patients with severe IgG2 deficiency (Ig2 less than 0.3 g/l) and 35 patients with non-detectable IgG4 in immunoprecipitation were detected . One of these patients had a concomitant IgA deficiency, eight revealed an additional IgA and IgG2 deficiency, two an IgA, IgG2, and IgG3 deficiency, eighteen an IgG2 deficiency and one patient an IgG2 and IgG3 deficiency . The proportion of patients with non-detectable IgG4 in immunoprecipitation was 13.5% and thus in the same order of magnitude as described in the literature for healthy people . Our data show that there is no relation between low IgG4 serum levels and the increased occurrence of severe infections . In all patients investigated with non-detectable IgG4 in immunoprecipitation the gene for the heavy chain gene constant domain C gamma 4 could be detected by Southern blotting . Using a sensitive ELISA method IgG4 could be directly demonstrated in all patients at a serum level of 0.5-29 micrograms/ml . Specific IgG4 antibodies against protein antigens could not be detected in IgG4-deficient patients . Nevertheless total IgG antibodies against diphtheria and tetanus toxoid reached protecting titers . Patients with IgG2 deficiency showed an impaired immune response against polysaccharides from pneumococci and haemophilus influenzae type b. Exp Lung Res, 1988, 14(1), 67 - 83 Inhibition of human neutrophil elastase by bacterial polyanions; Vered M et al.; We previously demonstrated that pneumococcal extracts contain a highly specific inhibitor of human neutrophil elastase (HNE) . We now show that the active inhibitor in these extracts is a high-molecular-weight, heat-stable substance that appears to be RNA, since inhibitory activity of pneumococcal extracts is decreased by incubation with ribonuclease but not by incubation with deoxyribonuclease or proteinase K . Moreover, metabolically labeled ({3H}uridine) pneumococcal RNA, isolated by phenol extraction followed by ethanol precipitation, strongly inhibits HNE . Pneumococcal capsular polysaccharide, although polyanionic, is only weakly inhibitory toward HNE and is not a major source of elastase-inhibitory activity in pneumococcal extracts . On the other hand, the capsule of Haemophilus influenzae type b contains polyribosylribitol phosphate . This highly charged polyanion possesses HNE-inhibitory activity, but only under special circumstances to be discussed below . Pneumococci (type I, type II smooth, type II rough) and H . influenzae (type b) all release HNE-inhibitory activity into their culture medium during growth . By contrast, Klebsiella pneumoniae and Staphylococcus aureus release little (if any) stable HNE-inhibitory activity during growth . We propose that some bacterial pneumonias may spare host tissue because polyanions released by the invading microorganisms (e.g . RNA from autolysing pneumococci) inhibit elastase released from inflammatory neutrophils and thereby modulate accompanying tissue proteolysis . Pneumonias caused by microorganisms that do not release stable polyanionic inhibitors of HNE (e.g., Staphylococcus and Klebsiella) may be correspondingly more injurious to the lung. Eur J Biochem, 1987 Dec 30, 170(1-2), 185 - 92 Structure of the capsular polysaccharide of Haemophilus pleuropneumoniae serotype 5; Altman E et al.; The capsular polysaccharide of Haemophilus (Actinobacillus) pleuropneumoniae serotype 5 (ATCC 33377) was found to be a linear type polysaccharide of a repeating disaccharide unit composed of 2-acetamido-2-deoxy-D-glucose and 3-deoxy-D-manno-2-octulosonic acid (dOclA) . By composition analysis, methylation, partial hydrolysis and 1H and 13C nuclear magnetic resonance studies, it was concluded that the capsular polysaccharide is a high-molecular-mass unbranched polymer having the structure: {6)-alpha-D-GlcNAcp-(1-5)-beta-dOclAp-(2}n. Presse Med, 1987 Dec 16, 16(43), 2156 - 60 {Evaluation of the bactericidal curves of beta-lactam and aminoglycoside combinations at the concentrations obtained in the cerebrospinal fluid in Haemophilus influenzae meningitis}; Bingen E et al.; The prognosis and sequelae of patients with Haemophilus influenzae meningitis were related to concentrations of bacteria in the cerebrospinal fluid (CSF) . Rapid bacterial killing and rapid reduction of organisms in vivo in CSF are critical to the outcome . In our patients colony counts of Haemophilus influenzae in CSF were 10(2)/ml - 10(9)/ml (mean 10(5)/ml) . Killing kinetics were determined for amoxicillin and cefotaxime, alone and in combination with amikacin, against 35 clinical strains of Haemophilus influenzae (43% beta-lactamase-positive) at concentrations of these antibiotics comparable to those attained in the CSF following systemic administration . Antibiotics concentrations were: amoxicillin: 5 mg/ml, cefotaxime: 3.8 mg/l, amikacin: 1.8 mg/l . Mean killing curves with beta-lactamase-negative strains showed that a bactericidal effect was observed at 18 h for amoxicillin, at 5 h for cefotaxime, at 5 h for amoxicillin plus amikacin and at 2 h 30 for cefotaxime plus amikacin . Against beta-lactamase-positive strains a bactericidal effect was observed at 5 h for cefotaxime, at 2 h 30 for cefotaxime plus amikacin and at 18 h for amoxicillin plus amikacin . The finding of significantly increased killing rates of Haemophilus influenzae by amikacin at low concentration in the presence of either ampicillin or cefotaxime suggests that combined therapy may be beneficial in the treatment of meningitis caused by Haemophilus influenzae. Pharm Weekbl Sci, 1987 Dec 11, 9 Suppl, S60 - 3 Treatment of acute exacerbations of chronic bronchitis with ciprofloxacin; Hoogkamp-Korstanje JA et al.; Thirty four patients with acute purulent exacerbations of chronic bronchitis were treated with 500 mg ciprofloxacin twice daily, orally, for ten days . Short time cure rate was 97% (cure 71%, improvement 26%) and failure 3%, long time cure rate (six months follow-up) was 74% . Predominant initial pathogens were Haemophilus influenzae and Streptococcus pneumoniae, mostly in pure cultures . All sputum cultures except those with Streptococcus pneumoniae became negative on the third day of treatment . Apart from a slower clearance of pneumococci from sputum there were no significant differences in responses between pneumococcal and Haemophilus infections during and after therapy . Mild adverse gastrointestinal effects were noticed in five patients. Pharm Weekbl Sci, 1987 Dec 11, 9 Suppl, S68 - 71 The use of ciprofloxacin in the treatment of patients with cystic fibrosis; van den Broek PJ et al.; The use of ciprofloxacin for the treatment of pulmonary infection in cystic fibrosis patients was investigated . Therapy was successful in six patients and unsuccessful in three patients . In one patient therapy had to be stopped because serum transaminase levels showed a 5- to 8- fold increase . During therapy resistance developed in Haemophilus influenzae, Staphylococcus aureus and Pseudomonas aeruginosa. Pharm Weekbl Sci, 1987 Dec 11, 9 Suppl, S53 - 7 Respiratory infections: clinical experiences with the new quinolones; Davies BI et al.; Nearly 300 patients, admitted to hospital with acute purulent exacerbations of chronic respiratory disease, have been treated with various newer quinolones: 26 patients received enoxacin, 50 pefloxacin, 80 ciprofloxacin and 143 ofloxacin . Dosages varied from 400 mg once daily to 1000 mg twice daily . orally for five to 10 days . Patients were evaluated bacteriologically and clinically before, during and after treatment . Nearly all infections associated with Haemophilus influenzae and/or Branhamella catarrhalis were successfully eradicated . Some Streptococcus pneumoniae infections relapsed, some could not be eradicated, and a number of patients developed new infections with these organisms . Approximately half of the Pseudomonas aeruginosa infections were eradicated . Nearly all patients received concomitant theophylline but this only caused serious problems in those given 600 mg doses of enoxacin twice daily . Five patients given ciprofloxacin had to discontinue because of unwanted effects (mostly hallucinations), one patient given pefloxacin had gastric pain and two patients given ofloxacin developed a skin rash . Apart from the theophylline interaction, the unwanted effects did not appear to be dose-related . The best overall clinical results were noted after 800 mg doses of ofloxacin once daily for seven days. Br Med J (Clin Res Ed), 1987 Dec 5, 295(6611), 1445 - 6 Abnormal sweat electrolytes in symptomatic human immunodeficiency virus infection in a child; Skeoch CH et al.; A 3 1/2 year old girl presented with failure to thrive and a five month history of diarrhoea and recurrent cough . The results of sweat sodium tests suggested a diagnosis of cystic fibrosis; but atypical organisms were found (Haemophilus influenzae, Candida albicans, but no Staphylococcus aureus), she failed to respond to treatment, and her sweat sodium concentrations fell in response to fludrocortisone . She also had hyperglobulinaemia, neutropenia, and reduced numbers of T4 lymphocytes, which prompted the performance of a test for antibody to human immunodeficiency virus (HIV) . This proved positive, and she was treated with co-trimoxazole, zidovudine, and human immunoglobulin . Both parents and two siblings were also positive for HIV, though all had normal sweat sodium concentrations . Children with symptoms suggestive of cystic fibrosis but who also show atypical features, as in this case, should have their HIV state checked. Infect Immun, 1987 Dec, 55(12), 3192 - 6 Hemagglutinating activity of lipopolysaccharides from subgingival plaque bacteria; Okuda K et al.; Lipopolysaccharide (LPS) preparations from the Bacteroides species B . endodontalis, B . intermedius, B . denticola, and B . melaninogenicus and from Fusobacterium nucleatum, Haemophilus actinomycetemcomitans, Capnocytophaga gingivalis, and Eikenella corrodens directly agglutinated erythrocytes of some kinds of animals . LPSs from the Bacteroides species B . gingivalis, B . asaccharolyticus, B . corporis, and B . loescheii and from Capnocytophaga ochracea did not possess any hemagglutinating activity . Pretreatment of LPSs with lipase and phospholipase C completely eliminated the hemagglutinating activity . The hemagglutinating activity was also affected by human serum, saliva, colistin, and polymyxin B but was not affected by sugars, amino acids, EDTA, or proteolytic enzymes . The role of this hemagglutinating activity in colonization by these microorganisms of the periodontal region is discussed. Arch Fr Pediatr, 1987 Dec, 44(10), 875 - 7 {Acute hydrocephalus drained in emergency . Consequence of cerebellar infarction in Haemophilus meningitis}; Perrin C et al.; A 2 year-old child admitted for Haemophilus meningitis was immediately treated by adequate antibiotic treatment . Three days later multiple hypertonic strokes and periodic respiration occurred; a resuscitation was necessary . CAT scan showed an acute hydrocephalus with non visible 4th ventricle and low-density areas in both cerebellar hemispheres allowing the diagnosis of cerebellar infarction . External drainage of CSF was rapidly performed and maintained for 11 days with success . The child was secondarily discharged with temporary cortical blindness and persistent moderate static cerebellar signs . The etiology of the cerebellar infarction was likely to be an arterial thrombosis in the vertebro-basilar area, probably secondary to cerebral arteritis related to Haemophilus. Antimicrob Agents Chemother, 1987 Dec, 31(12), 2018 - 9 Bactericidal activity against Haemophilus influenzae of cerebrospinal fluid of patients given amoxicillin-clavulanic acid; Decazes JM et al.; Patients with purulent meningitis received amoxicillin-clavulanic acid (200/20 mg/kg {body weight} per day) . Clavulanic acid levels in cerebrospinal fluid were less than or equal to 0.05 micrograms/ml in 5 of 18 samples and ranged from 0.1 to 0.8 micrograms/ml in the others . Of 12 cerebrospinal fluid samples tested, 10 lacked bactericidal activity in vitro against a beta-lactamase-producing strain of Haemophilus influenzae. Antimicrob Agents Chemother, 1987 Dec, 31(12), 1871 - 3 In vitro activities of aztreonam, imipenem, and amoxycillin-clavulanate against ampicillin-resistant Haemophilus influenzae; Powell M et al.; Two hundred and fifty-seven ampicillin-resistant clinical isolates of Haemophilus influenzae were tested by disk diffusion and MIC determination for susceptibility to aztreonam, imipenem, and amoxycillin combined with clavulanate . The modal MICs and MICs for 50 and 90% of isolates of all three antimicrobial agents for the 157 beta-lactamase-positive strains did not differ significantly from figures obtained with 2,201 ampicillin-susceptible H . influenzae by the same methods . Aztreonam and amoxycillin-clavulanate were less active, as reflected by an increase in these parameters, against 38 beta-lactamase-negative isolates requiring greater than or equal to 4 micrograms of ampicillin per ml for inhibition and 62 strains considered to have an intermediate degree of nonenzymic (intrinsic) resistance to ampicillin (zone diameters of less than 20 mm with 2-micrograms ampicillin disks and MICs of 1 or 2 micrograms/ml) . There was no detectable difference in imipenem activity against these 100 strains compared with that observed against the ampicillin-susceptible group . Of the 24 strains requiring at least 4 micrograms of imipenem per ml for inhibition, 13 also showed reduced susceptibility to ampicillin (5 beta-lactamase-positive and 8 beta-lactamase-negative isolates) . A lack of correlation between reduced susceptibility to imipenem and the other beta-lactams was observed. Arch Dis Child, 1987 Dec, 62(12), 1220 - 3 Haemophilus influenzae meningitis in Sweden 1981-1983; Trollfors B et al.; Four hundred and seventy cases of meningitis caused by Haemophilus influenza in children and 30 cases in adults were identified in Sweden between 1981 and 1983 . The age specific incidence in the most susceptible age group (0-4 years) was 31/100,000/year (440 cases), which is higher than previously reported from Europe . A further 30 cases were seen in children aged 5-14 . The risk of developing H influenzae meningitis before the age of 15 was 1 in 669 . There were 11 deaths (2%) and five cases of serious neurological sequelae among the children . Only 18 children (4%) had predisposing diseases . All but one of the 294 strains of H influenzae from children that had been serotyped were type b . Infections in adults differed from infections in children . Five of the adults died (17%), 12 had important predisposing diseases, and at least six of the infections were caused by non-typable strains . It is concluded that research into the prevention of invasive H influenzae infections in children should have high priority. Am J Vet Res, 1987 Dec, 48(12), 1678 - 83 Activity of beta-lactamase inhibitor sulbactam plus ampicillin against animal isolates of Pasteurella, Haemophilus, and Staphylococcus; Girard AE et al.; Antibiotic susceptibilities of Pasteurella sp, Haemophilus pleuropneumoniae, and Staphylococcus aureus isolates were determined . The combination of sodium sulbactam, a beta-lactamase inhibitor, and ampicillin had a synergistic effect against all ampicillin-resistant pathogens, rendering them susceptible to ampicillin . Studies of cell-free beta-lactamase from Pasteurella and Haemophilus isolates confirmed the presence of a constitutive penicillinase . Inhibitory concentrations of sulbactam-ampicillin were bactericidal, as demonstrated by killing curves . Ampicillin-resistant Pasteurella and Haemophilus isolates did not develop resistance to sulbactam-ampicillin when passed as many as 8 times in the presence of sublethal concentrations of sulbactam-ampicillin . The in vitro synergistic activity of sulbactam-penicillin also was seen in an in vivo synergistic response in mice challenge exposed to an ampicillin-resistant P haemolytica. Pediatr Res, 1987 Dec, 22(6), 708 - 13 Altered antibody isotype in cystic fibrosis: impaired natural antibody response to polysaccharide antigens; Moss RB et al.; Patients with cystic fibrosis (CF) have impaired natural (preinfection) IgG2 antibody responses to Pseudomonas aeruginosa lipopolysaccharide . To investigate the basis for this defect, we measured natural IgG and IgG1-4 antibody levels to Haemophilus influenzae type b polyribophosphate (PRP) and tetanus toxoid by enzyme-linked immunosorbent assay in 24 adult CF patients and 20 normal controls . Immunoglobulin heavy- and light-chain allotypes were determined on 146 Caucasian CF patients and 96 controls . The tetanus toxoid-specific IgG response was predominantly IgG1 . CF and control subjects had similar IgG and IgG1 antibody levels . The PRP-specific IgG response was predominantly IgG2 . In contrast to tetanus toxoid results, CF patients had lower geometric mean level of PRP-specific IgG compared to normal controls (p = 0.0036) . ELISA results were confirmed by liquid-phase 3H-PRP-binding assay: CF patients had a geometric mean serum antibody level of 395 versus 922 ng/ml in controls (p = 0.0044) . PRP-specific IgG2 levels were also depressed in CF patients (p = 0.03) . CF patients had a lower prevalence of the A2m(2) allotype than the local racially matched control sample (p less than 0.025) . Other allotype prevalences including G2m(n) and Km(1) were similar . Impaired IgG2 antibody responses to microbial polysaccharide surface antigens in CF patients might predispose them to persistent endobronchial infection and lead to production of nonopsonizing isotype responses . The potential role of A2m(2), coded for in the H chain locus on chromosome 14, is unknown, but could be related to mucosal IgA2 antibody responses. J Clin Microbiol, 1987 Dec, 25(12), 2339 - 43 Serum antibody response to capsular polysaccharide, outer membrane, and lipooligosaccharide in children with invasive Haemophilus influenzae type b infections; Claesson BA et al.; Serum antibodies against capsular polysaccharide (CPS), outer membrane (OM), and lipooligosaccharide (LOS) from Haemophilus influenzae type b were measured by enzyme-linked immunosorbent assay in acute- and convalescent-phase sera from 21 children between 3 months and 4 years of age with invasive H . influenzae type b infections . As expected, the levels of anti-CPS antibodies in the acute-phase serum samples were low or not detectable, as were the levels of antibodies against LOS . In contrast, all children had detectable antibodies against the OM in the acute-phase serum sample, indicating that they are of little or no importance for protection . An antibody response to CPS was noted in 13 of the 21 patients, mainly in the older children . An antibody response to the OM was seen in 16 patients, with no evident relation to age . The antibody response to the OM preparation, which consisted of proteins and LOS, was probably directed mainly against the OM proteins, since only six children showed a response, usually of low magnitude, of antibodies to LOS. Am J Epidemiol, 1987 Dec, 126(6), 1190 - 7 Pharyngeal carriage and acquisition of anticapsular antibody to Haemophilus influenzae type b in a high-risk population in southwestern Alaska; Hall DB et al.; Haemophilus influenzae type b disease in Alaskan Eskimos is characterized by greatly increased disease incidence at younger ages . This suggests that Eskimo infants have increased exposure to the disease . Exposure was studied in 1982-1983 in children less than age three years who lived in four Eskimo villages, as well as in a random sample of their family members (354 people from 132 households) . During a 12-month period, up to four pharyngeal cultures and two serum specimens were obtained from each participant . Colonization with H . influenzae type b was relatively uncommon (overall 2.5% of cultures, 6.8% of individuals) and was not associated with age, sex, season, or prior incidence of disease in the village . Biotyping and outer-membrane-protein typing of H . influenzae type b isolates revealed homogeneity within villages, with differences between villages . Matched sera revealed a significant decline in H . influenzae type b capsular antibody in the course of the study year . However, pharyngeal carriage of H . influenzae type b was associated with increases in antibody for carriers and members of their households . Antibody levels were positively associated with age . Only one case of H . influenzae type b disease developed during the study . Low carriage of H . influenzae type b was coincident with low incidence of disease and declining levels of capsular antibody in these villages . Mechanisms for increased exposure which would not be reflected in high carriage rates may exist for these young children. J Clin Microbiol, 1987 Dec, 25(12), 2447 - 8 Arthritis caused by Haemophilus paraphrophilus and isolation of the organism by using an improved culture protocol; von Essen R et al.; A case of bacterial arthritis caused by Haemophilus paraphrophilus is presented . This is the first reported case of arthritis caused by this organism . Culturing joint fluid in blood culture bottles provides for bacteria that are slow growing or present in small numbers. Vet Microbiol, 1987 Dec, 15(4), 303 - 14 Preparation and characterisation of envelope proteins from Haemophilus pleuropneumoniae; Rycroft AN et al.; Envelope proteins of Haemophilus pleuropneumoniae were extracted by 3 methods and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) . Three major envelope proteins (45,000 Mr, 41,000 Mr, 31,500 Mr) were distinguished in sonicated cell envelopes together with minor proteins . Using selective solubilisation with sodium lauryl sarcosinate or Triton X-100, outer membrane proteins were distinguished from those of the cytoplasmic membrane . Extraction into LiCl produced a similar profile, but the 41,000 Mr and 31,500 Mr bands were present in reduced amounts . Extraction into saline at 60 degrees C produced a grossly different pattern, with a major band at 20,000 Mr . All 3 major envelope proteins were shown to be heat-modifiable, and the 31,500 Mr band was found to be the non-heat-modified form of a 43,000 Mr protein, which showed similar properties to the Protein d of H . influenzae which is related to the OmpA protein of E . coli K-12 . The 45,000 Mr major protein was also weakly associated with the peptidoglycan in SDS/Triton at low temperature. Pathol Biol (Paris), 1987 Dec, 35(10 Pt 2), 1377 - 81 Changes in expression of bacterial surface antigens induced by antibiotics and their influence on host defenses; Gemmell CG; Concomitant with the discovery that a number of antibiotics were able to induce profound morphological changes (increased septation, thickened walls, filamentation) at low concentrations their ability to inhibit bacterial protein/polysaccharide synthesis was determined . In particular toxin and extracellular enzyme biosynthesis could be repressed by the lincosamines, fusidic acid, erythromycin and streptomycin in Staphylococcus aureus, Streptococcus pyogenes, Propionibacterium acnes, Pseudomonas aeruginosa and Escherichia coli . Several of these exoproducts act as antigens associated with microbial virulence and are therefore of importance in pathogenicity . Likewise structural components such as fimbriae in Escherichia coli, M protein in Streptococcus pyogenes, protein A in Staphylococcus aureus and capsule in Bacteroides fragilis and Haemophilus influenzae were not synthesised when the producer bacteria were grown in low concentrations of antibiotic . These products, through their importance as impedins of opsonization and subsequent phagocytosis by white blood cells, are important determinants in the host-parasite relationship . By their loss during drug exposure, potentiation of opsonophagocytosis occurred leading to more rapid killing of the pathogen . The immunogenicity of the antibiotic-damaged bacteria was also changed under these circumstances. Aust Paediatr J, 1987 Dec, 23(6), 323 - 7 Epidemiology and prevention of invasive Haemophilus influenzae type b infection; Gilbert GL; The use of rifampicin prophylaxis is recommended in close contacts of individuals with invasive Haemophilus influenzae type b infection if they include a child less than 4 years old in whom the risk of secondary infection is relatively high . In practice, delays in administration of rifampicin, contra-indications to its use and the difficulty of identifying all contacts at risk can reduce significantly its efficacy . Only 1-2% of cases of H . influenzae type b diseases are attributable to known contact and, at best, rifampicin prophylaxis can have little impact on the incidence . In the USA, one in 200 children less than 5 years old is affected . The incidence is probably similar in Australia but there are local differences which could affect the value of preventative measures . The vaccine recently licensed in the USA is not effective in children less than 18-24 months of age in whom the incidence of invasive H . influenzae type b infection, other than epiglottitis, is highest . Nevertheless, it could prevent more than 30% of cases if given to children at the age of 24 months . Vaccines effective in younger infants should become available soon . The best chance of prevention is by the optimal use of both rifampicin prophylaxis and immunization. Pediatr Emerg Care, 1987 Dec, 3(4), 253 - 5 Cerebral herniation syndrome as the presenting sign of Haemophilus influenza meningitis; Bonadio WA; A child who presented with cerebral herniation syndrome which was subsequently found to be a complication of bacterial meningitis is reported . The approach to the initial emergency department management of such a patient is discussed, as is the literature which summarizes this unusual complication. Pediatr Infect Dis J, 1987 Dec, 6(12), 1080 - 4 Outpatient treatment of serious community-acquired pediatric infections using once daily intramuscular ceftriaxone; Dagan R et al.; Pediatric patients with serious infections are usually hospitalized for parenteral antibiotic treatment . We studied prospectively 74 pediatric patients with community-acquired serious infections and used once daily intramuscular ceftriaxone . Seventeen patients (23%) were initially hospitalized and 57 (77%) patients were treated entirely as outpatients . An initial intramuscular dose of 75 mg/kg was followed by daily doses of 50 mg/kg (maximum, 1.5 g) . Infections treated included periorbital/buccal cellulitis, other cellulitis, urinary tract infections, pneumonia, osteomyelitis, mastoiditis, suppurative arthritis and orbital cellulitis . Organisms were recovered from cultures of 37 (50%) patients and 6 (8%) patients were bacteremic . Bacteria included Gram-positive (mostly Staphylococcus aureus) and Gram-negative (mostly enteric bacilli and Haemophilus influenzae organisms) . No serious side effects were observed . Of 74 patients 72 (97%) were cured and improvement was usually observed within 24 hours . Two patients did not improve: one with chronic Pseudomonas mastoiditis; and one with lung abscess . Based on previous experience it is estimated that 376 hospitalization days were saved . All 72 successfully treated patients and their parents resumed normal activity within 72 hours of starting therapy . Our data suggest that ceftriaxone can be used for outpatient treatment of some infectious diseases. Pediatr Res, 1987 Dec, 22(6), 659 - 66 Effect of Haemophilus influenzae type b lipopolysaccharide on complement activation and polymorphonuclear leukocyte function; Inzana TJ et al.; Purified lipopolysaccharide (LPS) from Haemophilus influenzae type b (Hib) was examined for its capacity to interact with human hemolytic complement, generate conversion products of C3, C4, and factor B, stimulate C5a activity, and affect human neutrophil chemiluminescence and phagocytosis . Salmonella typhimurium LPS and Salmonella minnesota Rb LPS (R345 mutant) were examined for comparison . Incubation of Hib LPS with human serum deficient in gamma-globulin or with normal human serum containing 10 mM EGTA and 7 mM MgCl2 resulted in some depletion of hemolytic complement and conversion of C3 to degradation products (determined by inhibition of passive hemolysis and electrophoresis/immunofixation, respectively), indicating that complement activation occurred by the alternative pathway . Complement activation by Hib LPS and S . minnesota Rb LPS was similar, but significantly less effective than by S . typhimurium LPS (p less than 0.01) . Solubilized Hib lipid A, but not LPS, induced conversion products of C4 in hypogammaglobulinemic serum, indicating activation of the classical pathway . Similar levels of C5a activity were generated by incubation of Hib LPS and S . typhimurium LPS in hypogammaglobulinemic serum, as determined by neutrophil shape change and neutrophil aggregation . Hib LPS directly stimulated neutrophil chemiluminescence, whereas S . typhimurium LPS had little effect . Phagocytosis of radiolabeled, opsonized Hib by neutrophils was diminished by S . minnesota Rb LPS, Hib LPS, or solubilized Hib lipid A (p less than 0.001), but was slightly increased by S . typhimurium LPS . Neither the oligosaccharide of Hib LPS or Hib capsular polysaccharide was capable of interacting with complement or altering neutrophil chemiluminescence or phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS) Infect Immun, 1987 Dec, 55(12), 2878 - 83 Biologic activities of antibody to a peptidoglycan-associated lipoprotein of Haemophilus influenzae against multiple clinical isolates of H . influenzae type b; Green BA et al.; A peptidoglycan-associated lipoprotein of about 15 kilodaltons was purified from the outer membranes of Haemophilus influenzae by using nondenaturing detergents . To assess its vaccine potential, rabbit antiserum to the purified protein was obtained . The antiserum was specific for the peptidoglycan-associated lipoprotein in whole cell lysates of H . influenzae and was bactericidal for H . influenzae types a, b, d, e, and f and for 181 of 182 H . influenzae type b clinical strains isolated in widely dispersed geographic areas . The antibody protected infant rats from challenge with each of five clinical H . influenzae type b isolates and was additive to and did not interfere with bactericidal and protective activities of antibody against the type b capsule . These data indicate that the purified peptidoglycan-associated lipoprotein is a potentially valuable vaccine candidate for H . influenzae type b disease and may enhance the effectiveness of preexisting anticapsular antibody. Vaccine, 1987 Dec, 5(4), 307 - 14 Synergistic effect of detergents and aluminium phosphate on the humoral immune response to bacterial and viral membrane proteins; Teerlink T et al.; The influence of detergents on the immunogenic activity of the major outer membrane protein of Neisseria gonorrhoeae was investigated . Most detergents tested were found to enhance the immune response . This effect was synergistic with the adjuvant activity of AlPO4 . The combination of detergent and AlPO4 showed a stronger adjuvant activity than Freund's complete adjuvant . The adjuvant effect was only observed with protein preparations with very low lipopolysaccharide content . The immunostimulating effect of detergents was also observed with meningococcal group C polysaccharide conjugated to a Haemophilus influenzae type b outer membrane protein and with the fusion protein of measles virus . The influence of some detergent parameters (critical micelle concentration, hydrophile-lipophile balance, charge) was investigated. Agents Actions, 1987 Dec, 22(3-4), 223 - 30 Effects of dietary poly-unsaturated fatty acids on tracheal histaminergic and cholinergic responsiveness in experimental models of bronchial hypersensitivity and hyperreactivity; Loesberg C et al.; Respiratory histaminergic and cholinergic receptor function was investigated in isolated tracheal spirals of guinea pigs receiving different diets . Comparison was made between saline treated (controls) and Haemophilus influenzae treated animals in non sensitized conditions, the latter being a model for bronchial hyperreactivity, and in sensitized conditions, being a model for allergen induced bronchial hypersensitivity . The different semi-synthetic diets (35 energy% fat), varying in linoleic acid content (5.85, 11.25 and 22.05 en% fat) and one diet with low linoleic acid (3.55 en%) in which linolenic acid was added additionally (5.30 en%), exerted profound effects on tracheal reactivity to histamine . In sensitized animals the maximal induced histamine contraction was significantly diminished in the dietary group receiving 5.85 en% linoleic acid as compared with the other dietary groups (35% decrease in the H . influenzae-treated, 20-30% decrease in saline treated animals) . Results in non-sensitized animals were similar, though less pronounced . No effect on food intake or growth of the animals could be demonstrated during the six week experimental periods . The carbachol induced contraction of the tracheal spirals of sensitized animals receiving low linoleic acid was also significantly decreased as compared to the other dietary groups (30% for saline treated and 20-30% for H . influenzae-treated animals) . No difference in carbachol responsiveness could be detected between the different dietary groups under non-sensitized conditions . The results are discussed in view of the current concepts for bronchial hyperreactivity, especially in relation to eicosanoid involvement. Antimicrob Agents Chemother, 1987 Dec, 31(12), 1948 - 54 Pharmacokinetic and in vivo studies with azithromycin (CP-62,993), a new macrolide with an extended half-life and excellent tissue distribution; Girard AE et al.; Azithromycin (CP-62,993), a new acid-stable 15-membered-ring macrolide, was well absorbed following oral administration in mice, rats, dogs, and cynomolgus monkeys . This compound exhibited a uniformly long elimination half-life and was distributed exceptionally well into all tissues . This extravascular penetration of azithromycin was demonstrated by tissue/plasma area-under-the-curve ratios ranging from 13.6 to 137 compared with ratios for erythromycin of 3.1 to 11.6 . The significance of these pharmacokinetic advantages of azithromycin over erythromycin was shown through efficacy in a series of animal infection models . Azithromycin was orally effective in treating middle ear infections induced in gerbils by transbulla challenges with amoxicillin-resistant Haemophilus influenzae or susceptible Streptococcus pneumoniae; erythromycin failed and cefaclor was only marginally active against the H . influenzae challenge . Azithromycin was equivalent to cefaclor and erythromycin against Streptococcus pneumoniae . In mouse models, the new macrolide was 10-fold more potent than erythromycin and four other antibiotics against an anaerobic infection produced by Fusobacterium necrophorum . Similarly, azithromycin was effective against established tissue infections induced by Salmonella enteritidis (liver and spleen) and Staphylococcus aureus (thigh muscle); erythromycin failed against both infections . The oral and subcutaneous activities of azithromycin, erythromycin, and cefaclor were similar against acute systemic infections produced by Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, or S . aureus, whereas azithromycin was more potent than erythromycin and cefaclor against the intracellular pathogen Listeria monocytogenes . The pharmacokinetic advantage of azithromycin over erythromycin in half-life was clearly demonstrated in prophylactic treatment of an acute mouse model of S . aureus infection . These properties of azithromycin strongly support the further evaluation of this new macrolide for use in community-acquired infections of skin or soft tissue and respiratory diseases. J Med Microbiol, 1987 Dec, 24(4), 309 - 13 The role of lipopolysaccharides in endotoxin-induced thymocyte proliferation and chondrocyte collagenase synthesis; Wilson M et al.; Crude endotoxin preparations from Haemophilus actinomycetemcomitans and Bacteroides gingivalis showed activity in the two principal bio-assays for interleukin 1--the lymphocyte activating factor assay and stimulation of chondrocyte collagenase synthesis . Lipopolysaccharides purified from the crude endotoxins had reduced activity in the chondrocyte collagenase assay . The activity of the endotoxins may be due to synergic interaction between their lipopolysaccharides and other, as yet unidentified, bacterial components. Infect Immun, 1987 Dec, 55(12), 2993 - 3000 Cloning and expression in Escherichia coli of the gene encoding the heat-modifiable major outer membrane protein of Haemophilus influenzae type b; Gonzales FR et al.; One major outer membrane protein (P1) of Haemophilus influenzae type b (Hib), with an apparent molecular weight of 34,000 (34K) as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), has been shown to be heat modifiable . After heating at 100 degrees C for 5 min in 2% SDS, the P1 protein exhibits an apparent molecular weight of 49,000 (49K) in SDS-PAGE . Monoclonal antibodies (MAbs) reactive with P1 bound to the surface of Hib, and one of these MAbs had a protective effect against the development of Hib bacteremia in an animal model for invasive Hib disease . A 6-kilobase Hib DNA insert containing the gene encoding this P1 protein was cloned into Escherichia coli by using the gamma gt11 expression vector . Recombinant phage expressing P1 were identified by screening phage plaques with a MAb directed against the P1 protein . Expression of the P1 protein by an E . coli lysogen carrying the recombinant phage was independent of both vegetative phage growth and induction of lacZ gene-directed transcription of the Hib DNA insert . The Hib DNA insert encoding the P1 protein was subcloned into the plasmid vector pBR322, and a transformant containing the recombinant plasmid pFRG100 was identified with the P1 protein-directed MAb in a colony blot-radioimmunoassay . Western blot (immunoblot) analysis determined that the recombinant P1 protein possessed heat-modifiability characteristics identical to those of the native Hib protein . The P1 protein was expressed on the surface of both the E . coli lysogen containing the recombinant phage and the E . coli transformant containing pFRG100 . Western blot analysis of acute- and convalescent-phase sera from infants with Hib meningitis showed that antibodies in the convalescent-phase sera recognized the P1 protein expressed by the E . coli transformant containing pFRG100 . The availability of this cloned Hib DNA insert encoding the Hib P1 protein and the expression of this protein on the surface of recombinant E . coli should facilitate the investigation of P1 for both its vaccinogenic potential and its functional role in the outer membrane of Hib. J Clin Microbiol, 1987 Dec, 25(12), 2434 - 6 Identification of Haemophilus influenzae type b by a monoclonal antibody coagglutination assay; Hamel J et al.; A coagglutination assay using monoclonal antibody is described for the identification of Haemophilus influenzae type b . An immunoglobulin G2a monoclonal antibody, Hb-2, directed against a serotype-specific outer membrane protein of H . influenzae type b was adsorbed to Staphylococcus aureus Cowan 1 cells . In a dot enzyme immunoassay, Hb-2 reacted with 453 of 455 H . influenzae type b isolates and did not react with H . influenzae of other serotypes, untypeable H . influenzae strains, or other bacterial species . The Hb-2 coagglutination assay was evaluated by testing 136 H . influenzae type b strains selected on the basis of multilocus enzyme genotypes, 5 strains of another serotype, and 94 untypeable H . influenzae strains . The specificity of the coagglutination assay was demonstrated by the inhibition of the reaction by free Hb-2 monoclonal antibodies . The coagglutination assay was as specific as the dot enzyme immunoassay and can be rapidly performed and easily interpreted. Infect Immun, 1987 Dec, 55(12), 2977 - 83 Cross-reactivity of surface-exposed epitopes of outer membrane antigens of Haemophilus influenzae type b; Loeb MR et al.; The cross-reactivity of exposed surface epitopes of outer membrane proteins from a spectrum of Haemophilus influenzae type b isolates that varied in their evolutionary distance from each other and in their outer membrane protein composition was analyzed by using an immunoblot assay . The results for outer membrane proteins a, n, and b/c were as follows . (i) A total of 13 of 14 strains possessing a protein a with similar mobilities on gels (i.e., the same apparent molecular weight) as protein a of strain Eag absorbed antibodies to protein a of strain Eag . These strains represented a broad spectrum on a scale of evolutionary distance . (ii) In contrast, only one of seven strains possessing a protein a with different mobilities absorbed these antibodies . (iii) Of five isolates close to strain Eag on the evolutionary scale, the four with a protein n with the same mobility as protein n of strain Eag absorbed antibodies to protein n of strain Eag . (iv) In contrast, of five isolates distant from strain Eag on the evolutionary scale, none absorbed antibodies to protein n, including one strain that had a protein n of the same mobility as that of strain Eag . (v) All strains that absorbed antibodies to protein b/c also absorbed antibodies to lipopolysaccharide, and the reverse of this was also true . Evolutionary distance and mobility of protein b/c on gels were not factors . Control experiments indicated that this result was an artifact due to the strong association of lipopolysaccharide with protein b/c on the gel and subsequent blot . The important conclusions from these experiments, especially pertinent for consideration of these proteins in either whole or peptide vaccines, are that proteins with apparently identical molecular weights can possess different surface-exposed epitopes, that proteins with different molecular weights can possess cross-reactive surface-exposed epitopes, and that some surface-exposed epitopes have been conserved even though the bacterium has undergone evolutionary divergence . In addition, experiments were also performed to determine whether H . influenzae type b strains maintained their integrity during the absorption step, i.e., incubation in antiserum . Strain Eag, which was used as a prototype type b strain, released a small proportion of its membrane (0.13%), but this did not result in exposure of epitopes that were usually buried . In contrast, strain S2, an unencapsulated mutant of strain Eag, was quite unstable, releasing three times as much membrane and a large proportion of its periplasmic proteins. Infect Immun, 1987 Dec, 55(12), 2902 - 11 Antigenic characterization of the oligosaccharide portion of the lipooligosaccharide of nontypable Haemophilus influenzae; Patrick CC et al.; Monoclonal antibodies (MAbs) directed against epitopes in the oligosaccharide portion of the lipooligosaccharide (LOS) of nontypable Haemophilus influenzae (NTHI) were used to characterize the LOS of this pathogen . Western blot (immunoblot) analysis with four LOS-specific MAbs and proteinase K-derived LOS preparations from 69 NTHI strains allowed the classification of these strains into nine LOS antigenic groups . The use of these MAbs in a more sensitive colony blot radioimmunoassay system together with these same NTHI strains identified 14 LOS antigenic groups . Extensive cross-reactivity was detected between the LOS epitopes of these NTHI strains and the LOS of H . influenzae type b . The epitopes recognized by these MAbs were not accessible to antibody on the surface of every strain . These LOS epitopes were also not stably expressed by NTHI growing in vitro; the observed frequency of LOS antigen variation ranged from 1 to 24% when large numbers of colonies of NTHI strains were screened for reactivity with the LOS-directed MAbs in the colony blot radioimmunoassay . This LOS antigenic variation was sometimes associated with alterations in the profile of the LOS molecule as resolved by dodecyl sulfate-polyacrylamide gradient gel electrophoresis followed by staining with silver . These data indicate that considerable antigenic diversity exists among NTHI strains with regard to the oligosaccharide epitopes in their LOS molecules. Med J Aust, 1987 Nov 16, 147(10), 485 - 9 Blood cultures in hospitalized children; McIntyre PB et al.; The results of 2439 blood cultures that were taken in an acute children's hospital over a two-year period were reviewed . Three hundred and twenty-two organisms were cultured from 310 patients . One hundred and thirty-five (5.5%) isolates were considered to be pathogenic and 187 (7.7%) isolates were considered to be contaminants . Coagulase-positive staphylococci and enteric Gram-negative organisms were the isolates of which the significance was most difficult to determine . Community-acquired bacteraemia that affected children of less than five years of age was caused by Haemophilus influenzae in 65% of cases . Staphylococcus aureus was the major pathogen in older children . In 20% of cases, antimicrobial agents were commenced or changed after blood culture results . Delayed or inappropriate therapy was significantly more common in patients without an apparent focus of infection . The results of our study suggest that narrow spectrum antimicrobial agents can be used as appropriate empiric therapy for unlocalized infections in previously-well children . In children of between three months and five years of age, treatment should be directed against Haem . influenzae and Streptococcus pneumoniae, and in children of over five years of age, antistaphylococcal therapy should also be included. N Engl J Med, 1987 Nov 5, 317(19), 1175 - 80 Antibiotic administration to treat possible occult bacteremia in febrile children; Jaffe DM et al.; We performed a prospective, randomized, placebo-controlled, double-blind clinical trial of antibiotic administration to treat possible occult bacteremia in febrile children . A total of 955 children aged 3 to 36 months with temperatures greater than or equal to 39.0 degrees C and no focal bacterial infection were enrolled at the emergency departments of two children's hospitals from January 1982 until July 1984 . Blood samples for culture were obtained, and the children were randomly assigned to receive either oral amoxicillin or placebo and were restudied approximately 48 hours after enrollment . Data were also collected on 228 children who could not be randomly assigned . Twenty-seven of the randomly assigned children (2.8 percent) had bacteremic infections with pathogenic organisms (Streptococcus pneumoniae, Haemophilus influenzae, and salmonella) . There were no differences in the incidence of major infectious morbidity associated with bacteremia between the antibiotic and placebo groups--2 of 19 patients (10.5 percent) in the antibiotic group and 1 of 8 (12.5 percent) in the placebo group--although the power for this comparison was low . Antibiotics reduced fever (P less than 0.005) and improved the clinical appearance (P = 0.07) in the children with bacteremia but not in those without bacteremia . Although there were no statistically significant differences in the incidence of side effects, diarrhea tended to occur more often in the patients treated with amoxicillin (15 vs . 11 percent, P less than 0.10) . We conclude that our data do not support the routine use of standard oral doses of amoxicillin in febrile children who do not have evidence of focal bacterial disease. Pediatrics, 1987 Nov, 80(5), 731 - 5 Haemophilus influenzae type b vaccine: use in the pediatric population; Gururaj VJ et al.; To assess the use of the Haemophilus influenzae type b vaccine and the attitudes of health professionals regarding its use in the pediatric population, we conducted a study of community clinics, health department clinics, university-based teaching clinics, and private practice groups in the state of Texas . Whereas 59.6% of the private practice groups and 57.1% of the university-based teaching clinics administered the vaccine to more than 75% of their eligible children, 72.7% of community clinics and 81.7% of health department clinics never administered the vaccine to their eligible children . Likewise, whereas 100% of the university-based teaching clinics and 95.7% of the private practice groups had the vaccine available to their patients, only 22.7% of the community clinics and 15.5% of the health department clinics did so . The two most common reasons given by health professionals concerning the nonuse of the vaccine were nonavailability and high cost of the vaccine . Our findings suggest that a large segment of eligible children do not have access to this important vaccine and that children who depend on community and health department clinics for their routine health care are particularly affected in this regard . Strategies identified to increase the use of the vaccine include providing vaccine free of charge, increasing patient awareness of the vaccine benefits, and passing mandatory state laws requiring vaccine administration before day-care enrollment. Antimicrob Agents Chemother, 1987 Nov, 31(11), 1841 - 2 In vitro susceptibility of Haemophilus influenzae to cefixime; Powell M et al.; The in vitro activity of cefixime against 2,458 clinical isolates of Haemophilus influenzae was determined . All the strains were inhibited by less than or equal to 2 micrograms of cefixime per ml, and the modal MIC was 0.03 micrograms/ml . Activity was unaffected by the presence of beta-lactamase produced by 157 isolates . Nineteen of the twenty-four isolates for which cefixime MICs were greater than or equal to 0.5 micrograms/ml were beta-lactamase negative but showed reduced susceptibility to ampicillin. Antimicrob Agents Chemother, 1987 Nov, 31(11), 1711 - 7 Ampicillin killing curve patterns of Haemophilus influenzae type b isolates by agar dilution plate count method; Woolfrey BF et al.; The responses of 20 ampicillin-susceptible Haemophilus influenzae type b clinical isolates to the bactericidal action of ampicillin were studied by using a modified agar dilution plate count method . A well-defined paradoxical effect was observed in each of the 24-h killing curve patterns for 19 of the 20 isolates, the remaining isolate showing a less-well-defined but suggestive paradoxical effect after 48 h of ampicillin exposure . For each isolate, the lowest 24-h persister percentage representing maximum killing (paradoxical trough percentage) occurred over a narrow range of concentrations immediately above the MIC, with such paradoxical trough percentages for the 20 isolates ranging from greater than 0.1 to less than 0.001% . Three isolates selected to represent slow, intermediate, and rapid responses were investigated by repetition of 24-h studies and by determination of expanded killing curve patterns . Resultant agar dilution plate count killing curve patterns were found to be reproducible and strain dependent and served to characterize each isolate . The paradoxical effect became more distinct with the prolongation of ampicillin action . Maximum killing was again evident for a narrow range of ampicillin concentrations immediately above the MIC, with persister percentages rising rapidly over the next few ampicillin concentrations to peak at 1 to 2 log10 increments higher than trough percentages . Based on the broad range of responses observed for the 20 isolates, the consistent presence of the paradoxical effect, and the time-dependent nature of bactericidal action, we suggest that the MBC and MBC/MIC ratios are inadequate indices of bactericidal action and that the all-or-none concept of "antimicrobial tolerance" should be abandoned. J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 39 - 46 Postantibiotic effect of roxithromycin, erythromycin, and clindamycin against selected gram-positive bacteria and Haemophilus influenzae; Kuenzi B et al.; Recent experimental work has shown that a so-called PAE (postantibiotic effect, i.e . persistent suppression of regrowth after short exposure of bacteria to the study drug in vitro) is a feature of most current antibiotics . However, marked quantitative differences were found between different types of antibiotics and also between Gram-positive and Gram-negative organisms studied . A PAE has not yet been demonstrated for roxithromycin, a new macrolide antibiotic . Therefore, we compared the PAE of roxithromycin, erythromycin, and clindamycin against laboratory strains and clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, Str . pneumoniae, and Haemophilus influenzae in vitro . Identical multiples of the MIC and identical exposure times resulted in similar PAEs for the three study drugs tested . Good correlations could be found between the area under the in-vitro concentration-vs-time curve (AUC) and PAEs . The longest PAE of 9.6 h was observed after exposure of Str . pneumoniae to 1.9 mg/l of roxithromycin for 6 h. J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 21 - 9 Roxithromycin alone and in combination with sulphamethoxazole against Haemophilus influenzae; Lapointe JR et al.; Haemophilus influenzae is only moderately susceptible to erythromycin but previous studies in vitro and in vivo have shown that it is fully susceptible when erythromycin is combined with sulphonamides . The purpose of this study was to evaluate whether the activity of the new macrolide antibiotic roxithromycin was improved after combination with sulphamethoxazole . One hundred and eighty fresh clinical isolates of Haemophilus influenzae, comprising 74 ampicillin-susceptible, beta-lactamase negative, and 106 ampicillin-resistant, beta-lactamase positive, strains, were tested for their susceptibility to erythromycin, roxithromycin, sulphamethoxazole, erythromycin-sulphamethoxazole and roxithromycin-sulphamethoxazole in a fixed ratio of 1:19 . Bacteriostatic and bactericidal synergy was found between roxithromycin and sulphamethoxazole more commonly than between erythromycin and sulphamethoxazole . Antagonism, was less common between roxithromycin and sulphamethoxazole than erythromycin and sulphamethoxazole . These results suggest that the in-vitro activity of roxithromycin is improved by combination with sulphamethoxazole, making this combination more attractive in the oral therapy of infections due to H . influenzae. J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 1 - 5 In-vitro activity of roxithromycin against respiratory and skin pathogens; Pechere JC et al.; The activity of roxithromycin was determined by a microdilution method, in comparison with erythromycin, spiramycin and josamycin . Roxithromycin and erythromycin showed very similar MICs against staphylococci, Streptococcus pneumoniae, Str . pyogenes and Haemophilus influenzae . In most cases, spiramycin and josamycin appeared similarly or more active . The activity of roxithromycin against Mycoplasma pneumoniae, Legionella spp., Chlamydia psittaci and, to some extent, against Pasteurella spp . was also assessed, by suitable in-vitro methods . Roxithromycin has a promising potential for treating selected skin and respiratory infections. J Antimicrob Chemother, 1987 Nov, 20(5), 663 - 9 Comparative bactericidal activity of cefixime, carumonam, enoxacin and roxithromycin with those of other antibiotics against resistant Haemophilus influenzae including beta-lactam tolerant strains; Bergeron MG et al.; One hundred isolates of Haemophilus influenzae including 50 beta-lactamase producing, five ampicillin-resistant non-beta-lactamase producing and five beta-lactam tolerant strains were tested for susceptibility (MICs and MBCs) to ampicillin, aztreonam, carumonam, cefixime, cefaclor, cefamandole, cefotaxime, imipenem, enoxacin, ciprofloxacin, roxithromycin, erythromycin, chloramphenicol, and co-trimoxazole, by a microdilution broth method . Cefotaxime, enoxacin and ciprofloxacin with MIC90 and MBC90 of less than 0.03 mg/l) were the most active antimicrobial agents tested . Cefixime, carumonam, aztreonam, and co-trimoxazole (MIC90 and MBC90 less than 0.25 mg/l) showed good activity against most strains . Roxithromycin and erythromycin had limited antibacterial activity (MIC90, 8 and 4 mg/l respectively) . There were no chloramphenicol-resistant strains . Five beta-lactamase-negative strains were resistant to ampicillin, cefaclor and cefamandole but susceptible to other beta-lactams tested . Different patterns of tolerance were observed: four of five tolerant strains were tolerant to ampicillin and cefamandole, three to cefixime, cefaclor and cefotaxime, one to aztreonam . One tolerant strain was a beta-lactamase producer . Two other strains were tolerant only to co-trimoxazole. J Antimicrob Chemother, 1987 Nov, 20(5), 645 - 56 Ampicillin resistance in Haemophilus influenzae: identification of resistance mechanisms; Reid AJ et al.; The incidence and mechanisms of ampicillin resistance (MIC greater than 1 mg/l) were investigated in 105 clinical isolates of Haemophilus influenzae collected in Edinburgh during 1983/4 . Fifteen (14.3%) ampicillin-resistant strains were identified and these were non-serotypable and comprised six biotypes . Isoelectric focusing and beta-lactamase-inhibition studies demonstrated that production of the TEM-1 beta-lactamase was the principal mechanism of resistance in nine (60%) strains . Radiolabelling revealed that one beta-lactamase-positive strain also had an unusual penicillin-binding protein (PBP) profit . No beta-lactamase activity was detected in the other six (40%) ampicillin-resistant strains . Two beta-lactamase-negative ampicillin-resistant strains had atypical PBP profiles . SDS-PAGE analysis showed that four beta-lactamase-negative ampicillin-resistant strains, including one with altered PBPs, exhibited outer membrane protein profiles which differed from those of sensitive strains of the same biotype . The ampicillin-resistance mechanism of the remaining strain could not be determined . Thus, several resistance mechanisms, either acting individually or in combination, are implicated in ampicillin resistance in H . influenzae. J Laryngol Otol, 1987 Nov, 101(11), 1144 - 50 The nasopharynx and under-aeration of the middle-ear; Metcalfe S; This study compared nasopharyngeal sepsis with under-aeration ear disease . Nasopharyngeal sepsis was assessed by culture taken directly from the surface of removed adenoid tissue . 156 cases were studied; 100 showed varying degrees of middle-ear under-aeration and 56 had no active ear disease or history of it . In addition, an assessment of post-nasal obstruction was made and this too was compared with middle-ear status . The conclusions suggested that, whilst normal ears can exist in the presence of accepted nasal pathogens, diseased ears are rarely seen in the absence of nasal sepsis . The degree of post-nasal obstruction seemed irrelevant . The commonest nasopharyngeal pathogen was Haemophilus influenzae and when found alone this had a particularly detrimental affect on middle-ear aeration, causing a significant incidence of mucoid middle-ear effusion in this group. J Clin Microbiol, 1987 Nov, 25(11), 2105 - 13 Improved medium for antimicrobial susceptibility testing of Haemophilus influenzae; Jorgensen JH et al.; The need for complex growth media has complicated routine susceptibility testing of Haemophilus influenzae because of antagonism of certain antimicrobial agents by the medium or because of difficulties in interpretation of growth endpoints . Haemophilus test medium (HTM) is a simple, transparent medium for broth- or agar-based tests with H . influenzae . HTM incorporates Mueller-Hinton medium with additions of 15 micrograms of hematin per ml, 15 micrograms of NAD per ml, and 5 mg of yeast extract per ml as growth-promoting additives . Agar or broth microdilution MICs of 10 antimicrobial agents for a collection of 179 H . influenzae isolates determined by using HTM compared favorably with MICs determined by the conventional agar or broth dilution methods recommended by the National Committee for Clinical Laboratory Standards . Disk diffusion tests performed with HTM allowed accurate categorization of susceptible and resistant strains and were easier to interpret than tests performed with Mueller-Hinton chocolate agar . A particular advantage of HTM was the reliability of broth- or agar-based test results with trimethoprim-sulfamethoxazole . The results of the study suggest modification of current National Committee for Clinical Laboratory Standards MIC-interpretive criteria for H . influenzae with amoxicillin-clavulanate, chloramphenicol, and trimethoprim-sulfamethoxazole . Error rate-bounded analysis of MICs and disk diffusion zone sizes also suggest modified zone-interpretive criteria for ampicillin, amoxicillin-clavulanate, chloramphenicol, and tetracycline with HTM or conventional media . Interpretive zone sizes are newly proposed for cefaclor and rifampin disk diffusion tests. J Clin Immunol, 1987 Nov, 7(6), 475 - 80 Haemophilus influenzae type b opsonins of intravenous immunoglobulins; Bender S et al.; Immunoglobulin G may be prepared by different methods for intravenous infusion and administered as replacement therapy for hypogammaglobulinemia . Intravenous immunoglobulins prepared by different methods were compared in vitro for their ability to opsonize Haemophilus influenzae type b in the absence of complement and subsequently induce neutrophil chemiluminescence . While the antibody contents, measured by an enzyme-linked immunosorbent assay and radioimmunoassay, were equivalent, the immunoglobulin prepared by a non-molecular modifying method (ion-exchange chromatography) had the greatest ability to induce bacterial-neutrophil interaction, measured by chemiluminescence, while a reduced and alkylated immunoglobulin had the least . Thus, preparative methods may have a profound effect upon the function of intravenous immunoglobulins . The biological function of immunoglobulins for clinical use can be compared easily by neutrophil chemiluminescence. J Pediatr, 1987 Nov, 111(5), 644 - 50 Priming and induction of Haemophilus influenzae type b capsular antibodies in early infancy by Dpo20, an oligosaccharide-protein conjugate vaccine; Anderson P et al.; A conjugate vaccine (Dpo20) was made by direct coupling of diphtheria toxoid and oligosaccharides obtained by periodate oxidation of Haemophilus influenzae type b capsular polysaccharide . This approach gave a higher multiplicity of saccharides per protein and greater immunogenicity in infancy than our previously studied conjugates . Thirty-three healthy infants received three sequential injections, and no serious side effects were observed . When Dpo20 was given with diphtheria-tetanus-pertussis vaccine at ages 2, 4, and 6 months, the geometric mean titer of anticapsular antibody rose to 5.9 micrograms/ml at age 7 months . Dpo20 given at 3, 5, and 7 months raised the mean to 3.2 micrograms/ml at 7 months (after two injections) and 15.4 micrograms/ml at 10 months . The antibodies included IgG and were bactericidal in vitro . Thus, antibody activities potentially protective against invasive H . influenzae b infections were induced in the most susceptible age range . The infants also became primed for mature-for-age responses to (unconjugated) polysaccharide vaccine given as a booster at age 12 months. Infect Immun, 1987 Nov, 55(11), 2830 - 3 Effect of complement depletion on anticapsular-antibody-mediated immunity to experimental infection with Haemophilus influenzae type b; Schreiber JR et al.; Antibody to the capsular polysaccharide of Haemophilus influenzae type b (Hib) was not protective in infant rats depleted of complement by cobra venom factor (CoVF) even when serum antibody levels were many times the minimum protective level . Partial protection from Hib infection was achieved in CoVF-treated rats only if they were passively hyperimmunized with large doses of immunoglobulin G Hib capsular polysaccharide antibody . In addition, nonimmune CoVF-treated rats had higher mortality and blood bacterial density than nonimmune rats with intact complement systems. Infect Immun, 1987 Nov, 55(11), 2612 - 8 Protection of infant rats from Haemophilus influenzae type b infection by antiserum to purified outer membrane protein a; Loeb MR; Protein a (46,000 molecular weight {46K}) was purified from outer membranes of Haemophilus influenzae type b by a relatively simple procedure . Spontaneously shed outer membranes from a 24-h, 12-liter culture of an unencapsulated variant of strain Eag were combined with outer membranes released from the cells by Tris buffer and extracted with the nonionic detergent octylpolyoxyethylene . The extract was then subjected to open column chromatography on Sephacryl S-200 and Trisacryl-carboxymethyl to yield 7.5 mg of protein a from 180 mg of outer membrane protein . Approximately 99% of the protein in this preparation was protein a; in addition, the preparation contained 1.25% (wt/wt) lipopolysaccharide and had a residual detergent/protein ratio of 1.6:1 (wt/wt) . Antibodies to the preparation were induced in rabbits by using alum as an adjuvant . As determined by immunoblotting, the great preponderance of antibodies induced were specific for protein a . However, very low levels of antibodies to several other outer membrane components, which were not apparent on gels of the pure preparation of protein a, were also induced . Preimmune and postimmune sera, after depletion of antibodies to capsular polysaccharide and lipopolysaccharide, were tested for biological activity against H . influenzae type b . Compared with preimmune serum, postimmune serum was bactericidal in vitro against strain Eag (the only strain tested) and offered significant protection (P less than 0.01) to infant rats against infection by all four strains tested, two of which had a protein a that was larger (47K) than the 46K protein a in the preparation . These results indicate that protein a should be considered as a vaccine to prevent H . influenzae type b disease. Infect Immun, 1987 Nov, 55(11), 2585 - 9 Genetic and phenotypic diversity among ampicillin-resistant, non-beta-lactamase-producing, nontypeable Haemophilus influenzae isolates; Mendelman PM et al.; Levels of genotypic and phenotypic diversity among 23 ampicillin-resistant, non-beta-lactamase-producing (Ampr NBLP) isolates of serologically nontypeable Haemophilus influenzae recovered from the respiratory tract were determined by multilocus enzyme electrophoresis, auxotroph testing in chemically defined media, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of penicillin-binding proteins (PBPs) . Twenty distinctive multilocus enzyme genotypes were identified, among which the average level of genetic diversity per locus was equivalent to that in the species as a whole . Hence, a single, recent origin for Ampr NBLP strains is excluded . Of the growth factors tested, a requirement for methionine was significantly associated with the Ampr NBLP phenotype . In contrast to the relative homogeneity of the PBP profiles of the ampicillin-susceptible strains tested (8 PBPs detected), the PBP profiles of the Ampr NBLP strains exhibited marked heterogeneity (5 to 10 PBPs detected) . Care should be taken in interpreting changes in PBP profiles and in associating these profiles with resistance for species such as H . influenzae that demonstrate variability. Res Vet Sci, 1987 Nov, 43(3), 410 - 2 Binding patterns of five monoclonal antibodies to Actinobacillus (Haemophilus) pleuropneumoniae; Lida J et al.; Five monoclonal antibodies were obtained after immunising mice with superficial antigens of three strains representing serovars 1 to 3 of Actinobacillus (Haemophilus) pleuro-pneumoniae . When tested in ELISA against the standard strains representing serovars 1 to 10, the monoclonal antibody raised against the standard strain of serovar 1 reacted only with that strain . Of the three monoclonal antibodies raised against the standard strain of serovar 3, one reacted with serovars 3 and 8 only, another with serovar 7 only and the third with the strains representing serovars 7, 9 and 10 . The monoclonal antibodies produced with the serovar 2 strain also reacted with a wide spectrum of strains, representing serovars 7 to 10. Biochem Cell Biol, 1987 Nov, 65(11), 960 - 7 Structure of the capsular polysaccharide of Haemophilus pleuropneumoniae serotype 3; Altman E et al.; The capsular polysaccharide of Haemophilus pleuropneumoniae serotype 3 (ATCC 27090) is composed of D-galactose (one part), 2-acetamido-2-deoxy-D-glucose (one part), glycerol (one part), and phosphate (one part) . From hydrolysis, dephosphorylation, methylation, and 1H and 13C nuclear magnetic resonance studies, the polysaccharide was found to be a high molecular weight polymer of a repeating trisaccharide unit, joined through monophosphate diester linkages and having the following structure: (formula; see text). J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 7 - 11 A review of the in-vitro activity of roxithromycin against genital pathogens; Ridgway GL; The in-vitro activity of roxithromycin against Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Treponema pallidum, Gardnerella vaginalis and Haemophilus ducreyi is reviewed . Roxithromycin demonstrated equivalent activity to erythromycin against N . gonorrhoeae, C . trachomatis, M . hominis, U . urealyticum, G . vaginalis and H . ducreyi . In a rabbit model for syphilis, potentially useful activity against T . pallidum has been demonstrated. J Antimicrob Chemother, 1987 Nov, 20 Suppl B, 145 - 52 Roxithromycin, a new macrolide antibiotic, in the treatment of infections in the lower respiratory tract: an overview; Gentry LO; Roxithromycin is a new macrolide antibiotic with good absorption and a longer half-life than erythromycin . Worldwide clinical studies to evaluate its efficacy and safety in the treatment of infections of the lower respiratory tract have achieved a clinical success rate of 89% with few and mild side effects . Double-blind studies comparing roxithromycin with cephradine, erythromycin ethylsuccinate and doxycycline in pneumonia, acute exacerbations of bronchitis in patients with chronic obstructive airways disease, and acute bronchitis have been done . The clinical response to comparative regimens has been similar and ranges from 60% response with either regimen in patients with chronic airways disease to 90% response in patients with acute bronchitis or pneumonia . Roxithromycin appears to be as effective as erythromycin or doxycycline for the treatment of either Streptococcus pneumoniae or Haemophilus influenzae infections . A large double-blind trial comparing cephradine and roxithromycin in 90 cases of bacteriologically confirmed pneumococcal pneumonia in South African gold miners resulted in a 93% and 100% respective clinical response rate . The bacteriological results revealed interesting results in this same study, in that cultures from 17% of patients receiving roxithromycin and 23% of those receiving cephradine remained positive for S . pneumoniae after therapy was finished and an excellent clinical response had been obtained . Side effects in all studies have been transient and mild, with an elevated transaminase value being the most common in both roxithromycin and erythromycin or cephradine regimens . Roxithromycin appears to be a safe and effective oral antibiotic for the treatment of pneumococcal pneumonia and other infections of the lower respiratory tract, and is as effective as erythromycin, doxycycline or cephradine. Thorax, 1987 Nov, 42(11), 889 - 91 Haemophilus influenzae pneumonia in Melanesian adults: report of 15 cases; Barnes DJ et al.; In a prospective study of 170 adult patients with acute pneumonia, Haemophilus influenzae was found to be the aetiological agent in 15 cases (8.8%) . The diagnosis in all cases was based on positive cultures of blood or percutaneous lung aspirate, or both . Chronic lung disease was significantly more common in patients with H influenzae pneumonia than in patients with pneumonia due to other organisms but age, sex, and smoking history did not differ significantly . Lobar consolidation was the most common radiological pattern, being present in 10 of the 15 cases . Type b was the commonest serotype isolated, but three cases were due to non-typable (non-capsulate) strains . All patients survived, responding well to treatment with penicillin, ampicillin, or chloramphenicol . Haemophilus influenzae should be considered as a possible cause of pneumonia in adults, particularly those with underlying chronic lung disease. J Clin Microbiol, 1987 Nov, 25(11), 2098 - 101 SIGNAL blood culture system for detection of bacteremia in neonates; Trombley C et al.; In the SIGNAL (Oxoid Ltd., Basingstoke, United Kingdom) blood culture system, gas produced by bacterial metabolism displaces medium from the culture bottle into an upper reservoir via a hollow needle . Displacement of media may provide a visual indication of the presence of both aerobic and anaerobic organisms in a single medium . The single-bottle SIGNAL system was compared with paired BACTEC 16B and 7D (Johnston Laboratories, Inc., Towson, Md.) radiometric system bottles by using bacterial inocula and conditions which simulated those found in neonatal and pediatric populations . The single SIGNAL bottle was a good as the combined BACTEC media for Escherichia coli and Staphylococcus aureus, but was slower for Candida spp., Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus epidermidis, group B streptococci, alpha-streptococci, and pneumococci . The SIGNAL system failed to detect four of five isolates of Neisseria meningitidis and four of eight anaerobic organisms . The SIGNAL system is not suitable for neonatal blood cultures at its present state of development. J Pediatr, 1987 Nov, 111(5), 783 - 8 Concentrations of antibodies in paired maternal and infant sera: relationship to IgG subclass; Einhorn MS et al.; Previous studies comparing IgG subclass concentrations in cord and maternal sera have indicated that IgG1 is transported across the placenta to a greater extent than is IgG2 . The purpose of our study was to examine the relationship between the transport of IgG1 and IgG2 and the transport of specific antibodies that are relatively restricted to a particular subclass, either IgG1 or IgG2 . The concentrations of total serum IgG1 and IgG2 and those of IgG-anti-tetanus toxoid (TT) and anti-group A streptococcal carbohydrate (GAC) were measured in 30 paired maternal and cord sera . Previous studies have shown that anti-TT in adults is predominantly IgG1, whereas anti-GAC is predominantly IgG2 . The mean cord/maternal concentration ratios of IgG1 and anti-TT were similar (1.77 +/- 0.56 and 1.93 +/- 0.67, respectively), but differed significantly (P = 0.0001) from those of IgG2 and anti-GAC (0.99 +/- 0.39 and 1.01 +/- 0.45, respectively) . We confirmed the difference in cord/maternal concentration ratios of IgG1 and IgG2 antibodies by measuring IgG1 and IgG2 antibodies specific for Haemophilus influenzae type b capsular polysaccharide; the mean cord/maternal concentration ratio of IgG1-anti-Hib PS was significantly higher than that of IgG2-anti-Hib PS (2.23 +/- 0.83 compared with 0.94 +/- 0.49, P = 0.01) . These results indicate that placental transport of IgG antibodies is related to their subclass composition. Rev Infect Dis, 1987 Nov-Dec, 9(6), 1140 - 9 Branhamella catarrhalis respiratory infections; Hager H et al.; Branhamella catarrhalis, a normal commensal of the oropharynx, is increasingly recognized as an important cause of bronchitis and bacterial pneumonia . Six patients with B . catarrhalis pneumonia documented by transtracheal aspirate or blood culture were studied, and 429 previously reported cases of B . catarrhalis bronchitis and pneumonia were reviewed . The mean age of patients with B . catarrhalis infection was 64.8 years, and preexisting chronic obstructive pulmonary disease was common . The typical clinical picture was that of purulent tracheobronchitis; patients with pneumonia were not severely ill and differed from those with bronchitis mainly by the presence of patchy lower-lobe infiltrates on chest roentgenogram . Fifty-three percent of reported strains produced beta-lactamase . Thirty-nine percent of the cultures were mixed, predominantly with Haemophilus influenzae and Streptococcus pneumoniae . The microbiologic, immunologic, and clinical features of B . catarrhalis infection, as well as the antimicrobial susceptibilities of this organism, were reviewed . The reasons for the lack of recognition of this common pathogen and possible solutions were considered. J Clin Microbiol, 1987 Nov, 25(11), 2223 - 4 Rapid identification of pathogenic Neisseria species and Branhamella catarrhalis; Hughes B et al.; Two systems, the Identicult-Neisseria (IDN; Scott Laboratories, Inc., Fiskeville, R.I.) strip and the Neisseria/Haemophilus Identification Test Kit (NHI; Vitek Systems, Inc., Hazelwood, Mo.) card, were compared with the 4-h Minitek system (BBL Microbiology Systems, Cockeysville, Md.) for their ability to rapidly identify 157 pathogenic Neisseria and Branhamella catarrhalis isolates . IDN, limited in its identification to four species, when incubated at 35 degrees C for 10 min identified 99% of the isolates . However, when IDN was incubated at 22 degrees C for 20 min, it identified only 92% of the isolates . The NHI card, a rapid semiautomated system with the ability to identify 25 organisms to the species level, correctly identified all of the isolates . A test for beta-lactamase production included in the NHI card identified the 12 Neisseria gonorrhoeae and 10 B . catarrhalis beta-lactamase-positive isolates included in the study . The IDN strip (35 degrees C) and the NHI card compared favorably with the Minitek system. J Infect Dis, 1987 Nov, 156(5), 723 - 31 Outer membrane protein and lipooligosaccharide analysis of paired nasopharyngeal and middle ear isolates in otitis media due to nontypable Haemophilus influenzae: pathogenetic and epidemiological observations; Murphy TF et al.; We studied isolates of nontypable Haemophilus influenzae from cultures of nasopharynx and middle ear fluid (MEF) done simultaneously on children with otitis media . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane protein (OMP) patterns demonstrated that in 16 of 19 pairs, the nasopharyngeal and MEF strains were identical . With four monoclonal antibodies to lipooligosaccharide (LOS) determinants, 17 of the 19 pairs were identical . Thus the pathogenesis of otitis media due to nontypable H . influenzae appears to involve spread of the bacteria from the nasopharynx to the middle ear . Analysis of middle ear isolates from four children with recurrent otitis media caused by nontypable H . influenzae indicated that the recurrent episodes were caused by reinfection with different strains rather than by persistence of the same strain . OMP and LOS analysis of strains from two sisters with concurrent otitis media suggested that person-to-person transmission of nontypable H . influenzae can occur among children. N Engl J Med, 1987 Oct 8, 317(15), 923 - 9 Prevention of Haemophilus influenzae type b infections in high-risk infants treated with bacterial polysaccharide immune globulin; Santosham M et al.; Apache Indian infants have a high frequency of Haemophilus influenzae type b (Hib) and pneumococcal infections . Forty percent of Hib infections in these infants occur before the age of six months, when active immunization may not be protective . To evaluate the efficacy of passive immunization with a human hyperimmune globulin (bacterial polysaccharide immune globulin {BPIG}) prepared from the plasma of immunized adult donors, we randomly assigned 703 infants in a double-blind fashion to receive 0.5 ml of BPIG per kilogram of body weight (n = 353) or 0.5 ml of saline (n = 350) intramuscularly at 2, 6, and 10 months of age . Hib-antibody levels were significantly higher in BPIG recipients than in placebo recipients at 4, 6, and 10 months of age (P less than 0.001) . During the first 90 days after BPIG or placebo injection, no Hib or pneumococcal infections were detected in the BPIG group, whereas seven Hib infections (six cases of bacteremia and one of meningitis) and four pneumococcal infections (bacteremia) were detected in the placebo group (P = 0.007 and 0.06, respectively) . During the fourth month, one case of Hib meningitis and two cases of pneumococcal bacteremia developed in the BPIG group, whereas there were no Hib or pneumococcal infections in the placebo group . We conclude that BPIG given at four-month intervals provided significant protection against serious Hib disease for three months, and that in high-risk infants it might be used alone, perhaps at three-month intervals, or together with active immunization. Lancet, 1987 Oct 3, 2(8562), 761 - 3 Haemophilus aegyptius bacteraemia in Brazilian purpuric fever . Brazilian Purpuric Fever Study Group; Brazilian purpuric fever: epidemic purpura fulminans associated with antecedent purulent conjunctivitis . Brazilian Purpuric Fever Study Group; In late 1984, 10 children in a small, rural town in Brazil had high fever associated with vomiting and abdominal pain . Within 12-48 h of the onset of fever, purpura developed associated with vascular collapse and peripheral necrosis . All 10 children died . Cerebrospinal fluid examinations did not suggest meningitis and, when done, tests were negative for Neisseria meningitidis . Other culture, serological, and necropsy examinations did not reveal a cause . Case-finding uncovered another cluster of similar illness in children in a second town and sporadic cases in five other cities . Two case-control studies demonstrated that children who became ill were significantly more likely than control children to have had conjunctivitis during the month before illness . This conjunctivitis was purulent, preceded the onset of more severe disease by 3-15 days, and had resolved before fever began . Although no conjunctival cultures were obtained from case-children, Haemophilus aegyptius was the most common pathogen isolated from other conjunctival cultures during the epidemic . This organism was also isolated from a non-aseptic skin scraping from 1 case child . A 25-megadalton plasmid distinguished the H aegyptius isolates epidemiologically associated with illness from other Brazilian conjunctival isolates . Brazilian purpuric fever is a newly recognized syndrome of epidemic purpura fulminans associated with antecedent purulent conjunctivitis, possibly caused by H aegyptius. Pediatr Infect Dis J, 1987 Oct, 6(10), 989 - 91 Bacteriologic and clinical efficacy of cefixime compared with amoxicillin in acute otitis media; Howie VM et al.; The ability of cefixime or amoxicillin to eradicate causative pathogens was evaluated in 140 infants and children with acute otitis media with effusion . When pretherapy and on-therapy bacteriologic cultures were used, success was defined as elimination of pathogens regardless of clinical improvement . Parent compliance with administration instructions was closely monitored . Cefixime was administered daily or twice daily and because results on the two dosage regimens did not differ, data were combined for analysis . Results suggested that cefixime was somewhat more effective than amoxicillin for acute otitis media with effusion caused by Haemophilus influenzae but less effective for infections caused by Streptococcus pneumoniae . The study agents were equally effective against Branhamella catarrhalis. Anal Biochem, 1987 Oct, 166(1), 36 - 40 Preparation of cell envelopes of large numbers of individual bacterial strains with the use of an automatic cell disruptor; Van Alphen L et al.; Analysis of the cell envelopes of large numbers of bacterial strains is used for the epidemiological and taxonomic investigation of clinical, veterinarian, and ecological isolates . Isolation of cell envelopes requires lysis of the bacteria . We developed an apparatus to disrupt bacterial cells of 200 different isolates in suspension by ultrasonication automatically . It is composed of modified standard laboratory equipment (fraction collector, cooling unit, pump), a standard ultrasonifier, and a newly designed control unit, which includes a sampler . This apparatus was applied to the analysis of cell envelope proteins of 96 Haemophilus influenzae strains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis within 3 days after the first culture. J Clin Microbiol, 1987 Oct, 25(10), 1985 - 8 Improved selective culture media for Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus; Holm A et al.; By modifying the previously described media tryptic soy-serum-bacitracin-vancomycin (TSBV) agar and tryptic soy-serum-bacitracin-vancomycin-fluoride (TSBVF) agar, two improved selective culture media were developed for isolation and enumeration of Actinobacillus actinomycetemcomitans (A medium) and Haemophilus aphrophilus (H medium) in oral specimens . Both media were supplemented with fusidic acid and spiramycin, and carbenicillin was also added to A medium . The growth yields of pure cultures of A . actinomycetemcomitans on A medium and of H . aphrophilus on H medium were comparable with those on the reference media . Compared with blood agar, the selective media inhibited these species about 10-fold or less . In addition, A and H media suppressed the growth of pure cultures of Capnocytophaga spp . and Neisseria spp., commonly found as contaminants on TSBV and TSBVF, 10(5) times or more compared with that on blood agar . In samples from diseased periodontal pockets, the recoveries of A . actinomycetemcomitans on A medium and H . aphrophilus on H medium equaled those on TSBV and TSBVF, respectively . In about 50% of the cultures on the reference media, contaminating bacteria were detected at levels higher than 10(4) CFU/ml of sample . The corresponding value for both A and H media was about 2%. Mayo Clin Proc, 1987 Oct, 62(10), 906 - 15 Tetracyclines, chloramphenicol, erythromycin, and clindamycin; Wilson WR et al.; The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and may also be used for gonococcal infections in patients unable to tolerate penicillins . These drugs may cause gastrointestinal irritation, photo-toxic dermatitis, diarrhea, vestibular damage, and hepatotoxicity in pregnant women . Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and typhoid fever . The most important toxic effect of chloramphenicol is bone marrow suppression, which can be dose related or idiosyncratic . Erythromycin is the drug of choice for the treatment of infections caused by M . pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae . The frequency of serious untoward effects associated with the use of erythromycin is low; epigastric distress may occur . Clindamycin is active against Bacteroides fragilis and other anaerobic microorganisms . Pseudomembranous enterocolitis has developed in as many as 10% of patients taking this drug . The use of clindamycin should be discontinued promptly if diarrhea occurs. Arch Fr Pediatr, 1987 Oct, 44(8), 607 - 8 {Facial cellulitis and Haemophilus meningitis in infants}; Blanc T et al.; Two cases of facial cellulitis due to Haemophilus influenzae serotype b are reported in 2 infants aged 3 and 6 months . Bacteriological diagnosis relied on blood cultures . Association with bacterial meningitis emphasizes the necessity of a systematic cerebrospinal fluid examination and the choice of antibiotherapy. Pediatr Res, 1987 Oct, 22(4), 438 - 41 Ampicillin-chloramphenicol-resistant Haemophilus influenzae: plasmid-mediated resistance in bacterial meningitis; Overturf GD et al.; A 4-month-old infant with congenital heart disease and sepsis and arthritis, and subsequently meningitis, caused by an antibiotic-resistant strain of Haemophilus influenzae type b, failed to respond to sequential therapy with ampicillin and trimethoprim/sulfamethoxazole . Following treatment with ceftizoxime, the infant was well for 42 days, until he returned to the hospital and died . A total of 10 Haemophilus influenzae type b isolates, all outer membrane protein subtype 51, was isolated from the pretreatment blood and synovium, cerebrospinal fluid and subdural fluids, and the petrous pyramids at autopsy . Pretreatment isolates had no detectable plasmid DNA, chloramphenicol acetyltransferase or beta-lactamase; the minimal inhibitory concentration for ampicillin (AM) and chloramphenicol (CM) was 0.2 and 0.8 microgram/ml, respectively . However, all cerebrospinal fluid isolates had a 42-44 mD plasmid and produced chloramphenicol acetyltransferase and beta-lactamase; the minimal inhibitory concentration of these isolates to AM and CM were 12.5 and 25 micrograms/ml, respectively, and were also resistant to tetracycline and sulfonamide . Resistance to AM and CM was cotransferred by filter-mating conjugation at a frequency of one to two transconjugants per 10(5) to an Rd haemophilus recipient . Posttreatment isolates from the petrous pyramids also were resistant to AM and CM and produced chloramphenicol acetyltransferase and beta-lactamase activity, but had no plasmid DNA . These findings and data from genetic studies suggested that plasmid-bearing antibiotic-resistant Haemophilus influenzae type b was selected from a heterogenous population, and that the AM/CM resistance transposons were incorporated into the bacterial chromosome. J Clin Pathol, 1987 Oct, 40(10), 1174 - 7 Selenium and the growth of Haemophilus ducreyi; Vanden Berghe DA; One of the growth media in current use for Haemophilus ducreyi comprises Mueller Hinton agar, chocolatised horse blood, serum and IsoVitalex (BBL) . For a better understanding of growth factors, attempts were made to simplify this complex medium . The horse blood was replaced by haemin (200 micrograms/ml), the serum by albumin (0.2%), and IsoVitalex was substituted only by L-glutamine 0.01% . Most of the strains grew, but when selenium ions were added in a concentration of 3.25 x 10(-3) micrograms/ml, growth was stimulated and became more luxuriant than growth on conventional media. Am J Dis Child, 1987 Oct, 141(10), 1063 - 5 Haemophilus influenzae non-type b infections in children; Gilsdorf JR; During a four-year surveillance period in a tertiary care children's hospital, nine children experienced 11 episodes of Haemophilus influenzae non-type b invasive infections, representing 9% of all invasive H influenzae infections . Of these nine children, two had lymphoproliferative disorders; one had immunoglobulin subclass deficiency; one had severe congenital heart disease, with chronic heart failure; two had cerebrospinal fluid leaks; and two were premature neonates whose mothers had prolonged rupture of amniotic membranes . Only one child had no evidence of an underlying condition that might predispose him to infection with these ordinarily nonpathogenic organisms . Three of the isolates were serotype f, one was serotype e, and the remaining seven were nontypable, with types a through f antisera . Thus, the majority of children experiencing invasive H influenzae non-type b infections appear to have a predisposing medical condition . To aid in detecting these unusual infections, all H influenzae isolates from otherwise sterile body sites should be serotyped, and those children with non-type b isolates should be evaluated for a possible predisposing underlying illness. J Infect Dis, 1987 Oct, 156(4), 591 - 6 Safety and immunogenicity of Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) in infants; Lepow ML et al.; Safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) was evaluated in infants seven to 14 months of age . PRP-D (80% of subjects) or saline placebo (20%) was randomly and blindly administered (two doses separated by two months) . Incidence of mild reactions lasting less than 48 hr did not differ significantly between the placebo and vaccine recipients . Preimmunization levels of antibody to PRP were less than or equal to 0.15 micrograms/ml in 97% of subjects . A twofold increase in antibody concentration occurred in 88% of subjects following the first dose and in 99% following the second dose of vaccine . No change occ