Pediatrics, 1981 May, 67(5), 656 - 60 Pharmacokinetic comparison of intravenous and oral chloramphenicol in patients with Haemophilus influenzae meningitis; Yogev R et al.; The pharmacokinetics of chloramphenicol following intravenous and oral administration were studied in 14 infants with Haemophilus influenzae meningitis . Following five days of treatment with intravenous chloramphenicol (100 mg/kg/day every six hours), oral chloramphenicol was substituted at the same dose . Multiple serum levels of chloramphenicol were determined after an intravenous dose on day 4 and after an oral dose on day 10 . CSF levels were measured six hours after intravenous or oral chloramphenicol dose on those days (CSF trough) . Following intravenous administration, the mean peak serum level of 15.0 micrograms/ml was reached at 45 minutes . In comparison, after oral chloramphenicol in the same dosage, the mean peak serum level of 18.5 micrograms/ml was achieved at two to three hours . The mean serum half-life of the drug (6.5 hours) was significantly longer after oral administration than after intravenous chloramphenicol (4.0 hours) (P less than .001) . The increased serum half-life following orally administered chloramphenicol was occasionally associated with drug accumulation . In addition, mean trough CSF levels were somewhat higher when the patient received oral medication (6.6 micrograms/ml) compared to intravenous administration (4.2 micrograms/ml) (P less than .001) . For any treatment regimen for H influenzae meningitis that includes a period of oral chloramphenicol therapy the patient should be hospitalized to ensure compliance . Because of the wide range of individual variation in serum half-life that may result in accumulation, periodic monitoring of serum chloramphenicol levels is also recommended. Infect Immun, 1981 May, 32(2), 518 - 24 Comparative virulence of Haemophilus influenzae with a type b or type d capsule; Roberts M et al.; To determine the importance of specific capsule type in the pathogenesis of invasive Haemophilus influenzae disease, we compared the virulence of type b and type d strains isolated from different children with the virulence of transformation-derived type b and type d organisms . In addition, the unencapsulated derivative of these strains was also examined . Virulence was assessed by determining the ability of the strains to produce bacteremia with intranasal or subcutaneous inoculation . Unencapsulated derivatives were unable to cause bacteremia by any route; all type b strains (whether natural or derived by transformation), a natural type d, and a type d derived by transformation were able to produce bacteremia with similar frequency (42 to 62%) when 10(7) colony-forming units was given intranasally . Subcutaneous inoculation of 10(3) colony-forming units of strains with the type b capsule produced bacteremia at a greater frequency than did the strains with the type d capsule (P less than 0.002) . The type d isolate was more virulent than a mutagenized derivative of the strain . We conclude that the type b strains are more virulent than type d when inoculated subcutaneously. J Infect Dis, 1981 May, 143(5), 668 - 76 Subtyping isolates of Haemophilus influenzae type b by outer-membrane protein profiles; Barenkamp SJ et al.; Outer-membrane proteins from isolates of Haemophilus influenzae type b were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Sarcosinate-insoluble membrane preparations contained one peptide with a molecular weight of 16,000 and four major peptides with molecular weights of 25,000-40,000 . A peptide with a molecular weight of 49,000 (50,000 in some strains) was observed after the samples were heated at 100 C . Fifty-one isolates obtained from patients hospitalized with invasive diseases, primarily meningitis, could be subclassified into nine categories based on reproducible and clearly resolvable differences in the outer-membrane protein profiles . Five categories accounted for 92% of the isolates . Complete concordance was observed in subtypes of strains obtained from epidemiologically related cases and contacts . Thus, comparison of the major outer-membrane proteins of H . influenzae type b is a useful technique for investigating the transmission of the organism and may provide a basis for further immunologic characterization of the outer-membrane proteins. Arch Intern Med, 1981 May, 141(6), 795 - 6 Haemophilus influenza sepsis and shock secondary to biliary infection in an adult; de Sa Pereira M et al.; A 46-year-old woman was seen with biliary obstruction secondary to a pancreatic tumor . After undergoing a percutaneous liver biopsy, she became septic and went into shock . Haemophilus influenzae type be bacteremia and biliary infection were verified . With treatment, the patient recovered from the infection . Biliary infection by H influenzae is rare, and fulminant infections in adults are even more uncommon . Hazards of invasive diagnostic procedures in patients with obstructive jaundice are discussed. Am J Dis Child, 1981 May, 135(5), 410 - 2 Soft-tissue infections of ampicillin-resistant Haemophilus influenzae type b . The use of ampicillin and nafcillin in their treatment; Yogev R; The combination of intravenous ampicillin sodium and nafcillin sodium followed by oral ampicillin and dicloxacillin sodium was effective in treating five infants with soft-tissue infections and bacteremia due to beta-lactamase-producing, ampicillin-resistant Haemophilus influenzae type b . This antibiotic combination seems to be an effective alternative to chloramphenicol for treatment of non-meningitic invasive disease due to moderately ampicillin-resistant (minimum inhibitory concentration, 2 to 24 microgram/mL) H influenzae type b . The use of this combination should be in conjunction with appropriate in vitro tests whose results demonstrate synergism. Am J Dis Child, 1981 May, 135(5), 406 - 9 Ampicillin-resistant Haemophilus influenzae colonizing ambulatory children; Scheifele DW et al.; The prevalence of ampicillin sodium-resistant Haemophilus influenzae was determined from throat cultures of 305 ambulatory children . Resistant strains were detected in 3% of children, amounting to 12% of Haemophilus isolates . Factors associated with carriage of ampicillin-resistant strains were sought: only ampicillin exposure was significant . Among children who had received ampicillin or amoxicillin trihydrate within six months, 9% harbored ampicillin-resistant strains compared with 1.4% among those not exposed . Colonization with H influenzae was more frequent following the use of ampicillin, and a higher proportion of isolates was resistant rates was observed with other antibiotics or with factors such as age, sex, otitis history, or day-care center exposure . The association between ampicillin/amoxicillin usage and carriage of ampicillin-resistant strains is increasingly clear . It remains to be determined whether the use of newer antibiotics for otitis also will encourage the development of resistance in H influenzae. Lab Invest, 1981 May, 44(5), 434 - 41 Mechanism of potentiation of experimental Haemophilus influenzae type B disease in infant rats by influenza A virus; Myerowitz RL et al.; Intranasal infection of infant rats by virulent influenza A virus increases the frequency and magnitude of bacteremia induced by subsequent atraumatic intranasal inoculation of Haemophilus influenzae type b (HIb) . The mechanism of the "potentiating" effect was studied by histology, by measurement of the frequency and kinetics of bacteremia in rats preinoculated with virus, or a chemical irritant (0.1 N HCl), by comparison of the latter with physically "traumatic" bacterial inoculation, and correlation of these data with nasal HIb titers . Both virus and acid induced significant nasal inflammation which progressed following bacterial inoculation . A period of intranasal proliferation of HIb preceded bacteremia in rats preinoculated with either virus or acid . In contrast, bacteremia occurred almost immediately following physically traumatic bacterial inoculation suggesting that direct intravascular invasion had occurred under those circumstances . Repeated atraumatic inoculation of HIb or HIb followed by growth medium both produced a significantly increased frequently of bacteremia compared to a single inoculation, suggesting that the prolonged presence of large numbers of intranasal HIb was a factor in producing bacteremia and that virus or acid-induced mucosal inflammation may lead to elaboration of growth factors for HIb in nasal tissues. J Clin Invest, 1981 May, 67(5), 1482 - 9 A mucosal antibody response following systemic Haemophilus influenzae type B infection in children; Pichichero ME et al.; The possibility that mucosal antibody is produced as a host response to Haemophilus influenzae type b (Hib) infection was examined in this study . 17 of 18 prospectively evaluated children ranging in age from 2 mo to 7 yr developed a detectable level of anticapsular antibody in their nasopharyngeal secretions after systemic Hib infection . The mean concentration of nasal anti-capsular antibody of the 18 children was 554 ng/mg IgA (SD = 35-8,863) during the acute phase of illness and declined to 224 ng/mg IgA (SD = 19-2,688) in convalescence . Some children had mucosal antibody detectable at least 10 mo after infection . The mucosal antibody levels were not affected by the length of illness before diagnosis, type of disease, age of the patient, sex, or presence of detectable capsular antigen or viable bacteria in the nasopharynx . The mucosal antibody was predominantly of the IgA class and occurred independent of the serum antibody . Six of the children aged less than 1 yr who did not produce and/or sustain a serum antibody level correlated with protection demonstrated a persistent mucosal antibody response . These findings suggest that the mucosal immune system may have the ability to respond at an earlier age than the serum immune system and lead us to postulate that protective secretory antibodies to prevent systemic Hib disease may be inducible in young infants in spite of the poor serum antibody response occurring at this age. Antimicrob Agents Chemother, 1981 May, 19(5), 801 - 6 Therapy of lower respiratory tract infections with moxalactam; Lentino JR et al.; Moxalactam was evaluated in the therapy of lower respiratory tract infections in 40 patients . The most common organisms isolated were Streptococcus pneumoniae (37.2%) and Haemophilus influenzae (21.5%) . Gram-negative enteric organisms were isolated from six patients . No patient was evaluated as a treatment failure; however, two patients died of unrelated causes either during therapy or in the immediate posttherapy period . We determined the comparative minimal inhibitory concentrations of moxalactam, cefamandole, and cephalothin for our aerobic clinical isolates . Susceptibilities of the anaerobic isolates were measured by the Kirby-Bauer method . All isolates were susceptible to moxalactam . Moxalactam was found to be highly effective in the therapy of lower respiratory tract infections. Monatsschr Kinderheilkd, 1981 May, 129(5), 298 - 9 {Influenzae type B infections . Quick identification by countercurrent-immuno-electrophoresis (author's transl)}; Grubbauer HM et al.; Countercurrent immunoelectrophoresis (CIE) was performed in 16 patients with Haemophilus influenzae type b infection . Compared with the conventional methods CIE is a more accurate and rapid diagnostic tool . Even in patients already receiving antibiotics bacterial antigen can be detected by CIE in a high percentage . The methods are uncomplicated, inexpensive and possible to perform in any laboratory. JAMA, 1981 Apr 10, 245(14), 1456 - 9 Lumbar puncture-induced meningitis; Eng RH et al.; A retrospective study was done to evaluate the risk of lumbar puncture-induced meningitis . Fourteen percent (23/165) of patients with bacteremia caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitis, and groups A and B streptococci had spontaneous meningitis (without a preceding lumbar puncture) . In contrast, only 0.8% (7/924) of patients with blood culture containing other organisms had spontaneous meningitis and 2.1% (3/140) of these patients had clinical courses consistent with lumbar puncture-induced meningitis . However, the 2.1% incidence in the latter group is not significantly different from 0.8%, the expected incidence of spontaneous meningitis . It is suggested that if lumbar puncture-induced meningitis does occur, it is rare enough to be clinically insignificant. Nord Vet Med, 1981 Apr-May, 33(4-5), 236 - 49 {Pleuropneumonia in swine due to Haemophilus pleuropneumonia s . parahaemolyticus . II . Studies on the epidemiology and the relation to chronic pleuritis (pleural scars) in baconers (author's transl)}; Christensen G; Within a Danish practice area a serological examination was made of 268 breeding animals in 25 conventional sow herds with a view to screening for herd infection with haemophilus pleuropneumoniae . Average size of the herds was 76 year-sows including pregnant gilts (8--200) . In 23 herds produced weaners were fed for slaughtering . The frequency of chronic pleuritis in slaughtered baconers in these herds was related to the frequency of seropositive sows in the herds . Three SPF-herds were included in the investigation, a SPF baconer herd reinfected with H . pleuropneumoniae, a SPF baconer herd reinfected with Mycoplasma suipneumoniae and a SPF breeding herd infected with Haemophilus parasuis . Complement fixation antibodies against Haemophilus pleuropneumoniae were found in breeding animals in 22 out of the 25 conventional sow herds . The average incidence of seropositive breeding animals in infected herds was 62% (7%--100%), highest in the largest herds . Likewise the highest serotitres were found in the largest herds, as an expression of strong infection pressure in large herds . The highest titre values were found in boars and young sows . The frequency of seronegative sows was the highest among the oldest sows . The registered frequency of chronic pleuritis among baconers from the examined herds was found increasing along with higher frequency of seropositive sows in the herds . On the basis of these observations and on the basis of a comparison of chronic pleuritis frequency among baconers in six herds (two with high frequency of seropositive breeding animals, one with moderate frequency of seropositive breeding animals, and 3 SPF-herds, one of which had been reinfected with Haemophilus pleuropneumoniae, one reinfected with Mycoplasma suipneumoniae and one that had experienced an acute outbreak of Glasser's Syndrome) it is concluded that haemophilus pleuropneumoniae is the absolutely most important cause of chronic pleuritis in baconers . A pronounced seasonal variation was found in the monthly pleuritis frequency among baconers in herds strongly infected with Haemophilus pleuropneumoniae, the minumum frequency being in January-February, and the maximum frequency in July-October . It is supposed that the observed variation in frequency of chronic pleuritis is caused by changes in the environmental climate . High frequency of chronic pleuritis is caused by changes in the environmental climate . High frequency is found in the summer in slaughtered baconers, which have been clinically affected by pleuropneumonia as piglets and weaners under inferior climatic conditions during the colder season of the year. Int J Pediatr Otorhinolaryngol, 1981 Apr, 3(2), 137 - 43 Microbiology of chronic and recurrent otitis media with effusion in young infants; Stanievich JF et al.; Chronic otitis media with effusion (OME) has been assumed to be sterile, since several reports in the literature have described unsuccessful attempts to culture bacteria from it . However, several recent studies have confirmed an earlier report that there is a significant frequency of bacteria in the middle ears of children with chronic and/or recurrent OME . Similar studies in young infants with chronic and/or recurrent OME have not been previously reported . In this study, cultures were obtained at the time of myringotomy and tympanostomy tube insertion from 50 infants aged 1-12 months who had chronic and/or recurrent OME . From the 80 ears of 40 infants without cleft palate, 32% had bacteria isolated from their middle ears; 22% had Streptococcus pneumoniae or Haemophilus influenzae . In 21 of these ears, no effusion was apparent at myringotomy, but in 28% bacteria were isolated from middle ear washings . From the 20 ears of 10 infants with an unrepaired cleft palate, 55% had bacteria present in their middle ear aspirates; 50% had S . pneumoniae or H . influenzae . Even though the significance of bacteria in chronic OME in children, and now in young infants, is unclear at present, a therapeutic trial with an antimicrobial agent prior to surgical intervention would appear to be reasonable until such therapy is tested in a randomized, clinical trial. Can Med Assoc J, 1981 Apr 1, 124(7), 887 - 90 Meningitis in the central Arctic: a 4-year experience; Wotton KA et al.; There were 37 cases of meningitis during a 4-year period among the native and white populations served by the Churchill Health Centre in northern Manitoba, an annual incidence of 128 per 100 000 in the overall population and of 202 per 100 000 among the Inuit . Bacterial meningitis predominated; Neisseria meningitidis and Haemophilus influenzae each accounted for one third of the cases . There were five deaths, and 14 of the survivors had severe sequelae . Therefore, although the doctors and nurses involved in the study had improved access to telecommunication and air transportation services in caring for patients in isolated northern settlements, and despite their efforts to be vigilant for possible cases of meningitis and to begin vigorous treatment early, the incidence, morbidity and mortality of this disease remained relatively high, particularly among the Inuit. Pathol Biol (Paris), 1981 Apr, 29(4), 241 - 3 {Repartition of Haemophilus influenzae biotypes responsible of purulent meningitis . (Study of 50 strains) (author's transl)}; Denis F et al.; The repartition of the Haemophilus influenzae biotypes responsible of meningitis in world were reviewed . In Senegal the vast majority of strains of Haemophilus influenzae isolated from CSF belonged to biotype I (94%), the biotypes II and IV were rarely encountered (respectively 4% and 2%) . The biotypes of repartition in Africa is similar to this encountered in other world areas. J Clin Microbiol, 1981 Apr, 13(4), 738 - 41 Investigation of enzyme immunoassay time courses: development of rapid assay systems; Yolken RH et al.; An enzyme immunoassay (EIA) consists of a series of antigen-antibody reactions which result in the binding of an enzyme-labeled antibody to a solid phase . The performance time of an EIA determination is thus largely dependent upon the time required for the antigen-antibody reactions . In an attempt to develop a rapid EIA system, we investigated the time course of an EIA system for the measurement of Haemophilus influenzae type b polysaccharide . We found that, although the use of short incubations led to a decrease in sensitivity, an assay system utilizing 10-min incubation periods was still capable of detecting antigen at a concentration of 1 ng/ml . Important factors in the sensitivity of EIAs with short incubation times were the performance of the reaction at 37 degrees C and the incubation of the solid phase with constant agitation . Utilizing these techniques, we developed an EIA system for the measurement of H . influenzae type b polysaccharide which could be completed in less than 30 min . This system was sufficiently sensitive to detect H . influenzae polysaccharide in the cerebrospinal fluids of nine patients with proven H . influenzae meningitis . Thus, EIA systems utilizing short incubation times might be useful for the rapid detection of infectious antigens in body fluids. J Clin Microbiol, 1981 Apr, 13(4), 681 - 7 Minimum number of bacteria needed for antigen detection by counterimmunoelectrophoresis: in vivo and in vitro studies; Fung JC et al.; Threshold concentrations of Streptococcus pneumoniae type 3, Haemophilus influenzae type b, and Streptococcus sp . group B type Ib required for positive counterimmunoelectrophoresis reactions were determined in vivo and in vitro . Animals were infected intraperitoneally with various concentrations of microorganisms: adult mice with S . pneumoniae, suckling rats with H . influenzae, and 3-week-old mice with Streptococcus sp . group B . At 24 h after infection a minimum blood concentration of 10(3) colony-forming units (CFU)/ml was needed for S . pneumoniae or H . influenzae before antigen was detected in the serum . A minimum concentration of 10(6) CFU/ml was needed for Streptococcus sp . group B at 10 h after infection . Larger threshold concentrations (10(4) CFU/ml for S . pneumoniae, 10(5) CFU/ml for H . influenzae, and 10(7) CFU/ml for Streptococcus) were required in broth-grown cultures before cell-free antigens could be demonstrated by counterimmunoelectrophoresis in the medium . Marked levels of antigen release by group B streptococci were observed as the cultures entered early stationary phase . This study provides evidence of a long-accepted, though poorly substantiated, hypothesis that a threshold concentration of microorganism is necessary before counterimmunoelectrophoresis reactions become positive . Counterimmunoelecrophoresis results for clinical specimens should be interpreted cautiously in light of this evidence. J Neurosurg, 1981 Apr, 54(4), 484 - 8 Bacteriology of intracranial abscess in children; Brook I; The bacteriological and clinical findings in 19 pediatric patients with intracranial abscess are presented . Ten children presented with subdural empyema and nine had brain abscess . Sinusitis was present in 14 children, and dental abscess in two . The abscess was located in the frontal and parietal area in seven instances each, and in the temporal area in five . Anaerobic organisms alone were recovered in 12 (63%) of the patients (including eight with subdural empyema and four with brain abscess), aerobic bacteria alone were present in two children (11%), and mixed aerobic and anaerobic bacteria were present in five (26%) patients . There were 43 anaerobic isolates (2.3 per specimen) . The predominant anaerobes were anaerobic Gram-positive cocci (16 isolates); Bacteroides sp . (10, including two B . fragilis); Fusobacterium sp . (nine isolates); and Actinomyces sp . (five isolates) . A total of eight aerobic isolates (0.4 per specimen), including five Gram-positive cocci and three Haemophilus sp., were recovered . Antimicrobial therapy was administered to all patients . Five patients, four with sinusitis and subdural empyema and one with sinusitis and brain abscess, did not respond to antimicrobial therapy and aspiration of the abscess, and required surgical drainage of their inflamed sinuses . These findings indicate the major role of anaerobic organisms in the polymicrobial etiology of intracranial abscess in children. Antimicrob Agents Chemother, 1981 Apr, 19(4), 584 - 8 Penicillin-binding proteins in Haemophilus influenzae; Makover SD et al.; The penicillin-binding proteins (PBPs) of Haemophilus influenzae were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography . Eight major PBPs, ranging in molecular weights from 90,000 to 27,000, were detected . The pattern of molecular weights was different from that determined fro Escherichia coli or Pseudomonas aeruginosa . A study on the binding of several beta-lactam antibodies to the PBPs at their minimal inhibitory concentrations and at lower and higher concentrations revealed that all had highest affinity for PBP 2 . Amdinocillin (mecillinam) was an exception; it had highest affinity for PBP 3 . The morphological effects of several penicillins, cephalosporins, and amdinocillin on H . influenzae were similar to those reported for E . coli. J Infect Dis, 1981 Apr, 143(4), 548 - 53 Loss of plasmid DNA coding for beta-lactamase during experimental infection with Haemophilus influenzae type b; Daum RS et al.; Apparent R factor-negative segregation was documented during infection of infant monkeys with two of three strains of ampicillin-resistant Haemophilus influenzae type b . In vitro the bacterial population of one strain (A-Sm) uniformly produced beta-lactamase . All bacteria isolated from blood or cerebrospinal fluid from both animals inoculated with strain A-Sm produced the enzyme . In contrast, 98% and 96% of bacteria from two other strains produced beta-lactamase in vitro . After intranasal inoculation of infant Macacca mulatta with these two strains, bacteria isolated from blood and cerebrospinal fluid uniformly did not produce beta-lactamase . Loss of the beta-lactamase-producing phenotype was associated with loss of plasmid DNA . Strains containing a mixed population of bacteria may undergo spontaneous loss of plasmid DNA during experimental infection . It is suggested that in these strains the bacteria carrying plasmids are less virulent. J Infect Dis, 1981 Apr, 143(4), 517 - 24 The type b capsular polysaccharide as a virulence determinant of Haemophilus influenzae: studies using clinical isolates and laboratory transformants; Moxon ER et al.; Haemophilus influenzae organisms elaborating one of six capsular polysaccharides (types a-f) colonize the respiratory tract of humans, but only type b strains commonly cause systemic infections . To investigate the role of capsular polysaccharides as virulence determinants, rats were inoculated with capsulated (types a-f) or noncapsulated clinical isolates or with laboratory-derived type b and type d transformants of a noncapsulated strain . After intraperitoneal inoculation, all capsulated strains possessed the potential for systemic infection, but type b strains were more virulent; noncapsulated strains were noninvasive . After intranasal inoculation, only type b strains were invasive . There was no difference in efficiency of nasopharyngeal colonization between type b and type d transformants . After intravenous inoculation, only type b strains resulted in persistent bacteremia . Thus, type b strains--clinical isolates or transformants--display unique virulence characteristics . These data suggest that elaboration of type b capsule is necessary and sufficient for this virulence of H . influenzae type b in the rat. J Pediatr, 1981 Apr, 98(4), 531 - 6 Etiology of acute conjunctivitis in children; Gigliotti F et al.; To determine the etiology of acute conjunctivitis in children seen in pediatric practice, 99 patients with conjunctivitis and 102 age-and season-matched controls were cultured for aerobic bacteria including Haemophilus influenzae, and for viruses, Chlamydia trachomatis, and mycoplasmas . Agents statistically associated with conjunctivitis included H . influenzae (42% vs 0%), Streptococcus pneumoniae (12% vs 3%), and adenoviruses (20% vs 0%) . One of these three etiologic agents was isolated from 71 (72%) of the patients . Simultaneous infection with two pathogens was uncommon . Staphylococcus aureus was equally prevalent in diseased and control eyes; one strain of C . trachomatis was isolated from a control eye . Although there were variations in the clinical features of viral and bacterial conjunctivitis, differentiation in an individual patient was difficult . An adenovirus was isolated from 11 (65%) of 17 patients who had pharyngitis in addition to conjunctivitis . H . influenzae was isolated from 14 (74%) of 19 children who had both otitis and conjunctivitis . Adenovirus conjunctivitis was common in the fall and H . influenzae in winter. Am J Clin Pathol, 1981 Apr, 75(4), 557 - 9 A rapid paper-disc test for penicillinase; Tu KK et al.; A practical acidimetric assay for penicillinase production using penicillin and phenol red impregnated in paper discs was developed . Blank discs were first impregnated with buffered penicillin G and, after drying, with 1% phenol red . For use, a disc was added to a bacterial suspension made in saline solution . A yellow color within 1 to 30 min of incubation indicated penicillinase production . These discs were tested against Staphylococcus aureus, Haemophilus influenzae, and Neisseria gonorrhoeae, and the assay was found to be a simple, rapid, and accurate method for detection of penicillinase. Cell, 1981 Apr, 24(1), 33 - 40 The somatic replication of DNA methylation; Wigler M et al.; We have tested the hypothesis that DNA methylation patterns are replicated in the somatic cells of vertebrates . Using M-Hpa II, the modification enzyme from Haemophilus parainfluenzae which methylates the internal cytosine residues in the sequence 5'CCGG 3' GGCC, we methylated bacteriophage phi X174 RF DNA and the cloned chicken thymidine kinase (tk) gene in vitro and then introduced these DNAs and unmethylated controls into tk- cultured mouse cells by DNA-mediated transformation . Twenty-five cell generations later, the state of methylation of transferred DNA was examined by restriction endonuclease analysis and blot hybridization . We conclude that methylation at Hpa II sites is replicated by these cultured cells but not with 100% fidelity . We have also noted that methylation of the cloned chicken tk gene decreases its apparent transformation efficiency relative to unmethylated molecules. J Bacteriol, 1981 Apr, 146(1), 79 - 84 Uptake of plasmid deoxyribonucleic acid by Haemophilus; Gromkova R et al.; The uptake of circular and linear plasmid RSF0885 deoxyribonucleic acids, (DNAs) obtained from Haemophilus parainfluenzae 14, in both homologous and heterologous recipients was studied and compared with that of chromosomal DNA . High concentrations of divalent cations stimulated the uptake of either circular or linear plasmid DNA in H . parainfluenzae 14 competent cells but did not affect the uptake of chromosomal DNA . The biological activity of linear plasmid DNA was similar to that of circular DNA, and the transforming efficiencies for ampicillin resistance of both molecular forms were stimulated by divalent ions . Plasmid DNA was taken up efficiently either with or without the addition of divalent ions but was not biologically active in the heterologous Haemophilus influenzae Rd recipient . Our results suggest that in H . parainfluenzae 14 some of the steps for chromosomal and plasmid DNA uptake are different. N Engl J Med, 1981 Mar 26, 304(13), 749 - 54 Acute maxillary sinusitis in children; Wald ER et al.; We sought to correlate the clinical, radiographic, and bacteriologic findings in maxillary sinusitis in 30 children who had both upper-respiratory-tract symptoms and abnormal maxillary radiographs . Cough, nasal discharge, and fetid breath were the most common signs, but fever was present inconsistently . Facial pain or swelling and headache were prominent symptoms in older children . Bacterial colony counts of greater than or equal to 10(4) colony-forming units per milliliter were found in 34 of 47 sinus aspirates obtained from 23 children . The most common species recovered were Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis . No anaerobic bacteria were isolated . Viruses were isolated from only two sinus aspirates . There was a poor correlation between the predominant species of bacteria recovered from either the nasopharyngeal or throat culture and the bacteria isolated from the sinus aspirate . This study demonstrates that children with both upper-respiratory-tract symptoms and abnormal sinus radiographs are likely to harbor bacteria in their sinuses, suggesting that such children have bacterial sinusitis. JAMA, 1981 Mar 13, 245(10), 1043 - 5 Rifampin prophylaxis for contacts of Haemophilus influenzae type b disease; Cox F et al.; Rifampin prophylaxis (20 mg/kg once daily for four days) was used in close contacts of children with Haemophilus influenzae type b (HIB) disease . Two hours after a dose, the concentration of rifampin in serum and saliva exceeded the minimum bactericidal concentrations of organisms obtained from four of the carriers . In both a randomized prospective and an open study, nasopharyngeal carriage was eradicated in 37 (95%) of 39 contacts . No cases of serious H influenzae disease occurred in four to six months of follow-up . At the dose and treatment schedule used, rifampin was safe and effective for eradication of HIB carriage. Clin Pediatr (Phila), 1981 Mar, 20(3), 192 - 5 Fever in Haemophilus influenzae type B meningitis; Rutman DL et al.; Ninety-nine cases of Haemophilus influenzae type B (HIB) meningitis were analyzed to assess the causes of secondary and persistent fever and outcome of treatment . Secondary fever developed in 47 patients, 11 had persistent fever and 4 patients died . Secondary fevers were associated with intercurrent illness in 30 per cent, drug fever in 15 per cent, and neurologic complications in 13 per cent . Serious neurologic or other complications were no more common in patients with than in those without secondary fever . However, patients with persistent fever demonstrated a higher rate of neurologic complications . Neither persistent nor secondary fever are markers of bacteriologic relapse or inadequate therapy. Quad Sclavo Diagn, 1981 Mar, 17(1), 61 - 72 {Reliability of the bacterial identification tests and of antibiotic sensitivity tests made with automatic methods}; Goffi M et al.; A "MS-2 Microbiology System" (Abbott) has been used to identify and to assess the susceptibility patterns of clinically isolated bacteria from highly compromised patients . Automatically obtained results by the analysis of 300 specimens were compared to those of traditional methods . The automated system was in good agreement with API (81%) while in 4% of the strains there were major discrepancies, and 5% of the experiments were carried out with slow growing bacteria which normally give poor results in automatic systems . Antimicrobial susceptibility testing was satisfactory in 84% of the specimens with 7% of minor discrepancies and 9% of major ones . The evaluation of MIC for slow growing organisms like Haemophilus, Diplococcus and anaerobes belonging to the Bacteroides genus, was the same using either automatic or standard procedures. Jpn J Antibiot, 1981 Mar, 34(3), 287 - 304 {Laboratory and clinical studies on cefoxitin in pediatric field (author's transl)}; Iwai N et al.; Studies on antimicrobial activity, absorption and excretion and clinical use of cefoxitin in pediatric field were performed . 1 . MIC of cefoxitin was compared with that of cefazolin and/or ampicillin for clinical isolates of Staphylococcus aureus (36 strains), Escherichia coli (35 strains), Klebsiella pneumoniae (34 strains) and Haemophilus influenzae (80 strains) . MIC of cefoxitin against S . aureus was approximately 1-2 tubes higher than that of cefazolin . Many strains of E . coli and K . pneumoniae that showed high MIC to cefazolin were sensitive to cefoxitin . It is presumed that the results are due to the strong resistance of cefoxitin to beta-lactamase degradation . MIC of cefoxitin against H . influenzae was approximately 1-2 tubes lower than that of cefazolin, but approximately 4 tubes higher than that of ampicillin . 2 . Serum level and urinary recovery rate of cefoxitin after one shot i.v . injection of 25 mg/kg were examined . The serum mean levels were 33.8 microgram/ml at 1/2 hour, 7.0 microgram/ml at 1 hour and 2.9 microgram/ml at 2 hours after the injection, respectively, and the drug was not detected in serum at 4 and 6 hours after the injection . The mean half-life of serum level was 27.1 minutes . The mean urinary recovery rate within 6 hours after injection was 96.0% and most of the drug were excreted into urine within 2 hours after the injection . 3 . In order to evaluate clinical response, bacteriological response and side effects, cefoxitin was applied to 19 cases, i.e., 12 cases of either acute lobar pneumonia or acute bronchopneumonia, 2 cases of acute pyelitis, 1 case each of acute bronchitis, acute purulent tonsillitis, acute purulent arthritis, acute orbital phlegmon and acute buccal abscess . As for clinical response, the overall efficacy rate (the percentage of cases showed excellent and good efficacy) was 88.9% . As for bacteriological response, among the 13 strains which were determined or supposed to be causative organisms, i.e., 6 strains of Streptococcus pneumoniae, 2 strains of H . influenzae and 1 strain each of streptococcus pyogenes, alpha-Streptococcus, Enterococcus, E . coli and Neisseria sp., all strains were disappeared except for Enterococcus which was reduced by the treatment with cefoxitin . No side effect was observed in any case . Abnormalities of laboratory findings were observed in 3 cases, i.e., 1 case each of reduction of RBC and Hb, elevation of GOT and GPT and elevation of GPT, but all of them returned to normal following completion of the dosage term. Jpn J Antibiot, 1981 Mar, 34(3), 244 - 56 {Some experiences in the field of pediatrics with cefoxitin treatment by intravenous injections (author's transl)}; Hirama Y et al.; Following are the results obtained from studies made with cefoxitin in the field of pediatrics: (1) The peak serum level observed upon completion of the one hour drip infusion in a dose of 20-25 mg/kg of cefoxitin varied from 66.4 to 93.0 mcg/ml . This fell to a remarkably low level after 2 hours . The serum half-life varied from 18.84 to 27.86 minutes . (2) The cumulative quantity of cefoxitin excreted in the active form in the urine by the end of 6 hours after completion of the drip infusion was 92.9-93.8% . (3) All of the 42 patients with acute pediatric infection (such as various kinds of acute upper or lower respiratory tract infection, urinary tract infection were treated with either cefoxitin by a single shot (23 patients), or by drip infusion (19 patients) . The dosage employed was approximately 50-100 mg/kg/day divided into two to three treatments . There was no major difference in the clinical efficacy between administering two times or three times, the efficacy rates being 96% and 89% respectively . The overall efficacy rate was 93% . (4) In either case of intravenous injections by either a single shot or drip infusion, excellent clinical responses were obtained in most patients . These people had a variety of infections, which were considered to be caused by various kinds of Gram-positive cocci, E . coli (including ABPC resistance), P . mirabilis, Kl . oxytoca and Haemophilus . (5) Out of the 42 patients who received cefoxitin in a daily dose of 5-100 mg/kg divided into two or three times either by a single shot or drip infusion, no hepatic or renal function abnormality was observed except for 2 cases of temporary eosinophilia . (6) On the basis of these results, cefoxitin was found to be a highly useful antibiotic in the treatment of acute pediatric infection caused by microorganisms which are sensitive to cefoxitin. Jpn J Antibiot, 1981 Mar, 34(3), 237 - 43 {Clinical evaluation of cefoxitin in children (author's transl)}; Meguro H et al.; Cefoxitin (CFX) was evaluated for its safety and efficacy in children . Fifteen patients were treated with 73-125 mg/kg per day of CFX by intravenous administrations . The diagnosis of the patients were acute pharyngitis (4), pneumonia (2), pertussis and pneumonia (1), urinary tract infection (3); and the remaining 5 patients were esteemed to have nonbacterial infections . All the 10 patients of bacterial infections were cured after the CFX therapy . The pathogens recovered were Streptococcus pyogenes (1), Streptococcus pneumoniae (3), Haemophilus influenzae (2), Escherichia coli (2), enteropathogenic Escherichia coli (1), and Klebsiella pneumoniae (1) . All the strains isolated were susceptible to CFX, but the 2 isolates of Haemophilus influenzae had relatively high MIC values (12.5 mcg/ml) . Diarrhea (3 cases) and transient neutropenia (1 case) were found to be associated with the CFX therapy . However, no severe adverse reactions were encountered . Half-life of the serum level was short (24.1 minutes) and excretion into the urine was rapid . CSF concentration obtained 30 minutes after an intravenous injection of 50 mg/kg of CFX in 1 case with inflamed meninges was considerably high (8.3 mcg/ml) . CFX appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections. Nord Vet Med, 1981 Mar, 33(3), 121 - 33 {Pleuropneumonia in pigs due to Haemophilus pleuropneumoniae . I . A bibliographical review (author's transl)}; Christensen G; During the last twenty years pleuropneumonia in pigs, caused by Haemophilus pleuropneumoniae, has spread globally . The increasing importance of the disease within swine production is apparently connected with increasing industrialization and subsequent heavy concentration of a large number of animals in the individual production unit . Haemophilus pleuropneumoniae seems to be specific for pigs . Several more or less pathogenic serotypes of the bacterium are known . Serotype 2 as occurring in Denmark is primary pathogen for pigs which have not previously been in contact with the infection . Immunity of varying strength and duration is left after recovery . Prolonged immunity in an animal is presumably dependent on latent infection or on repeated infections . Normally there is a large number of latently infected animals in attacked herds . Such animals, especially sows and boars, represent a potential infection reservoir which might be the basis of new clinical outbreaks under conditions of reduced herd immunity or of compromised general resistance of animal groups . Clinical disease is most frequently seen in young pigs and fatteners, as piglets are generally protected by maternal antibodies . Acute pleuropneumonia is characterized by high temperature, lost appetite, light cough and often vomiting . Morbidity is high, especially by new-infection where there may also be considerable mortality if adequate antibacterial therapy is neglected, however, normally the disease implies low mortality . The pathological lesions are localized to the respiratory organs . The lungs are the seat of fibrinous necrotising pneumonia (red, grey hepatization), more or less extensive, most frequently of the diaphragmatic part of the lung . Furthermore fibrinous, later on fibrous pleuritis and pericarditis may be seen . The fibrous pleuritis may be of decisive diagnostical value when established with high frequency in baconers . The disease causes losses as a consequence of increased use of medicine and reduced daily weight gain in fatteners . Optimum environment and feeding conditions will reduce such losses considerably . The use of commercially available vaccines makes it possible to fortify specific resistance against the disease in exposed groups of animals . In small herds with few infected animals the infection may be eliminated by discarding seropositive animals, combined with strategic medication . Elimination of the infectious agent in large herds can only take place by replacing all animals by an SPF-herd. J Pediatr, 1981 Mar, 98(3), 485 - 91 Rifampin chemoprophylaxis for household contacts of patients with invasive infections due to Haemophilus influenzae type b; Daum RS et al.; To determine the efficacy of rifampin chemoprophylaxis in eradication of oropharyngeal carriage of Haemophilus influenzae type b, we conducted a multicenter, double-blind, placebo-controlled trial among household contacts of patients hospitalized for invasive HIB infection . Seventy-nine index patients and 400 close contacts were studied; 26.5% of contacts were colonized . The efficacy of rifampin (10 mg/kg/dose, 600 mg/dose maximum, twice daily for two days) in eradicating carriage was 52% and varied with age (75.6% in persons greater than or equal to 5 and 27% in those less than 5 years) . Eradication rates in those less than 5 years were not significantly better than for placebo . No resistant isolates were encountered in sensitivity testing . The low efficacy of this rifampin regimen in young children precludes its routine use as a chemoprophylactic agent for family contacts . The occurrence of three cases of invasive HIB infection in individuals outside the defined contact group raises concern regarding the efficacy of any chemoprophylactic regimen. Pediatrics, 1981 Mar, 67(3), 430 - 3 Nasopharyngeal carriage of Haemophilus influenzae type b: attempted eradication by cefaclor or rifampin; Yogev R et al.; The efficacy of cefaclor and rifampin in eradicating Haemophilus influenzae type b (HITB) from the nasopharynx of day care center and household contacts of children with HITB meningitis was evaluated . In 38/50 children treated with cefaclor, the carrier state persisted, a failure rate of 76% . Although cefaclor failed to eradicate HITB from many carriers, an appreciable reduction in the intensity of colonization following treatment was noticed . When rifampin was used in 17 children who had failed to respond to cefaclor, persistence of the carrier state with HITB was found in only two children, a failure rate of only 12% . During the study, two episodes of invasive HITB disease were documented to be acquired from sources other than the index cases or from children who were screened, which suggested the need to reevaluate the usually recommended strategy to screen for carriage and to treat only the immediate contacts 6 years of age and younger . Furthermore, the most appropriate agent for eradicating nasopharyngeal carriage of HITB awaits additional studies. J Clin Microbiol, 1981 Mar, 13(3), 540 - 7 Quantitative nephelometric determination of Haemophilus influenzae antigen in body fluids; Caceci T et al.; Nephelometry, an immunological technique widely used for the quantification of blood proteins, was adapted to provide a quantitative method of detecting Haemophilus influenzae capsular antigen in body fluids . Using specific antiserum directed against H . influenzae capsular antigen, samples of serum, cerebrospinal fluid, urine, and joint fluid from 38 cases of H . influenzae infections were analyzed . The results were compared for reliability to counterimmunoelectrophoresis, a widely used diagnostic tool . The nephelometric technique has the same advantages of speed and specificity as counterimmunoelectrophoresis and provides the clinician and researcher with a quantitative method that is as reliable as the qualitative counterimmunoelectrophoresis procedure . The method allowed directly quantitative readouts on patient specimens, with no necessity for serial dilutions or densitometric readings. J Clin Microbiol, 1981 Mar, 13(3), 532 - 9 Assessment of Haemophilus influenzae type b opsonins by neutrophil chemiluminescence; Kaplan SL et al.; A luminol-enhancement chemiluminescence assay and a radiolabeled uptake assay were developed to assess opsonins for Haemophilus influenzae type b . Opsonins in acute and convalescent sera from 17 children with H . influenzae type b meningitis, along with pooled normal human sera, were evaluated and compared with anti-polyribosephosphate antibody concentrations . Five children had a rise in the chemiluminescence-area under the curve for convalescent compared with acute sera . Patient chemiluminescence--area-under-the-curve values were significantly (P less than 0.05) more likely to exceed 50% of normal human serum values if sera contained greater than or equal to 0.1 microgram of anti-polyribosephosphate antibody per ml . Magnesium ethylene glycol tetraacetic acid chelation and heat inactivation of patient and normal human sera significantly (P less than 0.05) reduced chemiluminescence--area-under-the-curve activity . Thus, complement appears to contribute significantly to the opsonization of H . influenzae type b in sera of children . Two of nine children had increases in opsonins as assayed by 3H-labeled H . influenzae type b uptake . After natural systemic H . influenzae type b infection, young children are unable to respond acutely with an increase in anti-polyribosephosphate antibody or serum opsonic activity. Infect Immun, 1981 Mar, 31(3), 1125 - 31 Serological and biological activities of anti-Haemophilus influenzae ribosomal serum; Katz M et al.; The antibody content in serum from rabbits immunized with ribosomes from Haemophilus influenzae type b was determined by passive hemagglutination, enzyme-linked immunosorbent assay, and complement fixation . Attempts to use passive hemagglutination to assay anti-ribosomal antibodies were unsuccessful . In the enzyme-linked immunosorbent assay tests, rabbit antiserum was allowed to react with ribosomes that adhered to microtiter plates . The enzyme-linked immunosorbent assay method detected, in two ribosome-immunized rabbits and by 3 days postimmunization, titers which rose to plateaus on days 24 to 31 and declined thereafter . With the complement fixation method, the serum from one immunized rabbit also showed a titer on day 3 and reached a plateau on days 20 to 31 . Serum from the other immunized rabbit did not develop a titer until day 11; it reached a lower plateau on days 20 to 24 and then declined on days 27 to 55 . Although there were no apparent differences between the two immunized rabbits by the enzyme-linked immunosorbent assay, there were differences between the complement fixation antibodies in these rabbits . Passive protection experiments were performed with these sera . Maximal passive protection was achieved when mice were challenged intraperitoneally with 100 50% lethal doses of H . influenzae and immunized intravenously 1 h later with rabbit serum collected 27 days postimmunization . Rabbit anti-ribosomal sera were evaluated for bactericidal activity . Undiluted immune sera showed bactericidal activity; however, when diluted 1:10, activity was lost . Although bactericidal activities of immune sera were correlated to passive protection activities, it is unlikely that such protection was due to bactericidal antibodies . Immune serum had opsonizing activity since it enhanced phagocytosis of H . influenzae by mouse leukocytes. Am J Vet Res, 1981 Mar, 42(3), 468 - 73 Humoral immunity in experimental thromboembolic meningoencephalitis in cattle caused by Haemophilus somnus; Stephens LR et al.; Of 23 cattle inoculated IV with Haemophilus somnus, 16 (70%) died of thromboembolic meningoencephalitis . The inoculum was prepared from a minimally subcultured isolate of H somnus that was passaged through a calf by intracisternal inoculation immediately before use . Serum antibody titers, as measured by 7 serologic tests, were not correlated with the animal's susceptibility to infection . All cattle that died had a mean 4-fold increase in agglutination titer during the acute phase of the disease, 2 to 4 days after inoculation . Similarly, high acute-phase titers were demonstrated in 15 cattle with naturally occurring disease . Haemophilus somnus was isolated more frequently and in greater numbers from the CNS and urinary tract than from other organs of cattle that died. J Clin Microbiol, 1981 Mar, 13(3), 478 - 82 Diagnosis of bacteremia in children by quantitative direct plating and a radiometric procedure; La Scolea LJ Jr et al.; During a 1-year period, three bacteriological systems for detecting bacteremia in children were analyzed, namely, the BACTEC system (Johnston Laboratories, Inc., Cockeysville, Md.), the Fisher/Lederle bottle (Lederle Diagnostics, Pearl River, N.Y.), and a direct plating method of blood termed quantitative direct plating (QDP) . Of 2,123 blood cultures, 135 (6.4%) were positive; Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae accounted for 3.4%, representing 61 patients, other pathogens accounted for 0.6%, and contaminants accounted for 2.4% . Of 72 cultures yielding H . influenzae, N . meningitidis, and S . pneumoniae, 60 were recovered by both broth systems, 2 by BACTEC only and 10 by Fisher/Lederle bottle only . The BACTEC system failed to register a positive growth index reading by 24 h in 15 cultures which were positive for H . influenzae, even though growth had occurred, as shown by positive subculture and microscopy at this time . QDP detected 89% of the cultures positive for H . influenzae and N . meningitidis, of which 55% yielded results before either broth procedure . Only 50% of the cultures positive for S . pneumoniae yielded growth on QDP . This difference in the recovery rate probably is accounted for by the number of organisms in the blood . Thus, more than 100 organisms per ml of blood were found in 71% of cultures positive for H . influenzae and N . meningitidis but in only 7% of those positive for S . pneumoniae . These studies, then, have revealed that H . influenzae, which grew well in BACTEC broth, did not, however, give a significant growth index reading during day 1 of incubation, in contrast to N . meningitidis and S . pneumoniae . The QDP system not only provided information on the magnitude of bacteremia due to H . influenzae and N . meningitidis but frequently allowed earlier diagnosis and, thus, proved to be a valuable, simple, and inexpensive supplementary technique for broth cultures, although not for the diagnosis of S . pneumoniae bacteremia. J Infect Dis, 1981 Mar, 143(3), 495 - 8 Frequency of ampicillin-resistant Haemophilus parainfluenzae in children; Scheifele DW et al.; Ampicillin resistance has been described in Haemophilus species other than Haemophilus influenzae, but its frequency and significance are uncertain . In a throat-culture survey, beta-lactamase-producing Haemophilus parainfluenzae was detected in 192 (72%) of 266 ambulatory children . Ampicillin-resistant H . parainfluenzae was more frequently found in children from three to four years of age (88%) or in those who attended day-care programs (97%) and less frequently in older children and parents (33%) . Colonization was unrelated to previous exposure to antibiotics or to a history of otitis media . Colonization with ampicillin-resistant H . parainfluenzae occurred in 88% of subjects with H . influenzae, including all of seven subjects carrying ampicillin-resistant H . influenzae . Colonization with beta-lactamase-producing H . parainfluenzae was 26 times more frequent than with H . influenzae . If the mechanisms and genetics of resistance are the same, H . parainfluenzae may prove to be a vector for spread of resistance genes of H . influenzae. J Bacteriol, 1981 Mar, 145(3), 1189 - 95 Effect of ethylenediaminetetraacetic acid on deoxyribonucleic acid entry and recombination in transformation of a wild-type strain and a rec-1 mutant of Haemophilus influenzae; Noteborn M et al.; In transformation of Haemophilus influenzae, donor deoxyribonucleic acid (DNA) enters into competent cells in the presence of ethylenediaminetetraacetic acid (EDTA), which prevents the formation of single stranded regions in the donor DNA that has entered . If after entry of DNA the recipient cells were first incubated at 17 degrees C and then at 37 degrees C in the continuous presence of EDTA, almost no integration occurred . On the other hand, if after entry of DNA the cells were incubated first at 17 degrees C in the absence of EDTA, allowing the generation of single-stranded regions (integration is blocked at this temperature), and then at 37 degrees C in the presence of EDTA, donor-recipient DNA complexes were formed . These results suggest that single-stranded regions are required for integration . Integration to completion was strongly inhibited by EDTA . In a rec-1 mutant of H . influenzae no donor-recipient DNA complexes carrying recombinant-type activity were formed during incubation at 37 degrees C in the absence of EDTA . If rec-1 cells were incubated at 37 degrees C in the presence of EDTA, which strongly inhibited breakdown of DNA, donor-recipient DNA complexes were formed if previously single-stranded regions in the donor DNA that had entered were generated by incubation at 17 degrees C in the absence of EDTA . This suggests that the rec-1 protein protects the initial donor-recipient DNA complex against degradation, so that further steps in the recombination process can proceed. Nouv Presse Med, 1981 Feb 26, 10(8), 647 - 9 {Cefotaxime in digestive tract infections (author's transl)}; Paris J et al.; Cefotaxime was administered alone to 25 patients, with serious infectious diseases secondary to a gastrointestinal lesion . The largest group consisted of pancreatic and biliary infections, or infectious complication in cirrhotic patients . The daily dose was 2 or 3 g, sometime 4 g of cefotaxime . In the 15 cases where the infecting organisms could be identified: E . coli: 6, Staphylococcus aureus: 4, Klebsiella: 2, Haemophilus: 1, Proteus: 1 and Pseudomonas: 1, the pathogen was eradicated bacteriologically within two to six days after the onset of therapy . The infection was controlled in all 25 cases within 2 to 8 days even though, in 11 cases, previous antibiotic therapy had been insufficient, no complementary antibiotic treatment was associated and 8 of the cases with very severe infection were a serious problem to the intensive care unit . The use of cefotaxime is justified in the treatment of gastrointestinal infection even though pathogens are identified with difficulty in these diseases. Nucleic Acids Res, 1981 Feb 11, 9(3), 633 - 46 In vitro methylation of DNA with Hpa II methylase; Quint A et al.; The enzyme Hpa II methylase extracted and partially purified from Haemophilus parainfluenza catalyzes the methylation of the tetranucleotide sequence CCGG at the internal cytosine . The enzyme will methylate this sequence if both DNA strands are unmethylated or if only one strand is unmethylated . Conditions have been developed for producing fully methylated DNA from various sources . In vitro methylation of this site protects the DNA against digestion by the restriction enzyme Hpa II as well as the enzyme Sma I which recognizes the hexanucleotide sequence CCCGGG . These properties make this enzyme a valuable tool for analyzing methylation in eukaryotic DNA where the sequence CCGG is highly methylated . The activity of this methylase on such DNA indicates the degree of undermethylation of the CCGG sequence . Several examples show that this technique can be used to detect small changes in the methylation state of eukaryotic DNA. Jpn J Antibiot, 1981 Feb, 34(2), 171 - 9 {Some investigations on cefadroxil dry syrup (author's transl)}; Nakazawa S et al.; MIC of cefadroxil (CDX) against A group beta-Streptococcus was distributed between 0.05-0.2 microgram/ml, that is, more susceptible than cephalexin (CEX) an cefaclor (CCL), and susceptible to tetracycline (TC), erythromycin (EM), lincomycin (LCM) resistant strains . Serum level was higher than CCL administered orally at the same dose, and urinary excretion ratio after oral administration was good similarly to CEX and CCL . Patients treated were mostly scarlet fever and upper respiratory tract infections as acute tonsillitis and lacunar tonsillitis . They responded well to CDX at a daily dose of 30 mg/kg divided into 3-4 times . All cases of scarlet fever became normal temperature within 2 days . Among 14 cases in which A group beta-hemolytic Streptococcus was detected by pharyngeal sputum culture at admission, 11 cases became negative on the 1st day . This result was superior to CEX, when this drug was administered orally at a daily dose of 40-60 mg/kg, bacteria became negative at the ratio of 73.3% on the 2nd day . CDX was effective for acute tonsillitis, lacunar tonsillitis, acute bronchitis, impetigo and maxillary lymphadenitis in which numerous A group beta-Streptococcus, Staphylococcus aureus and Haemophilus influenzae were proven, as well as for acute urinary tract infection due to Escherichia coli . Clinical results of CDX in totalling 69 cases were excellent in 63 cases, good in 6 cases, efficacy ratio being 100% . No local nor systemic side effects were observed in 69 cases including maximum 11 days' treatment, as well as no effect was noticed on hepatic and renal functions . From the above results, it was concluded that satisfactory treatment results may be obtained with CDX dry syrup for children at a daily dose of 20-50 mg/kg divided into 3-4 times in acute infections due to CDX susceptible pathogens. Jpn J Antibiot, 1981 Feb, 34(2), 152 - 6 {Clinical investigation of cefadroxil in pediatric field (author's transl)}; Nanri S et al.; (1) Cefadroxil powder for syrup was administered in 24 cases of respiratory tract infection and urinary tract infection, and the efficacy was obtained in 21 cases, effective ratio being 87.5% . (2) Clinical effect could be obtained satisfactorily at a daily dose of 10-15 mg/kg divided into 3 times after each meal . (3) As to the side effect, GOT and GPT rose in 1 case, and stomatitis in 1 case, though the patients returned to normal after discontinuation of the drug . (4) Haemophilus appeared by pharyngeal culture after administration of the drug, and attention should be paid on an alteration of pharyngeal flora. Jpn J Antibiot, 1981 Feb, 34(2), 146 - 51 {Clinical results of cefadroxil in pediatric field (author's transl)}; Shinozaki T et al.; Cefadroxil was administered at a daily dose of 50 mg/kg in 113 children including acute respiratory tract infections suspected to be a bacterial infection and other febrile diseases . Among 41 cases in which pharyngeal culture was made twice before and after administration or urine and feces cultures were made, 20 cases (48.8%) were good bacteriologically, 5 cases (12.2%) were poor, and 16 cases (39.0%) were unknown . Clinical efficacy was obtained in 105 cases (92.9%) out of 113 cases . Microbial substitution was noticed in 12 cases (29.3%) out of the cases of which pharyngeal culture was made after cefadroxil administration . Haemophilus influenzae was detected newly after the administration in 7 cases (58.3%) out of these 12 cases . Bacteriological efficacy was obtained in 5 cases of acute respiratory tract infection of which pathogen was considered to be Haemophilus influenzae . No microbial substitution was noticed in these 5 cases . As to the side effects of cefadroxil administration, only a slight diarrhea was observed in 2 cases. Zentralbl Bakteriol A, 1981 Feb, 248(4), 488 - 93 Haemophilus influenzae type b capsular polysaccharide detection and measurement by an enzyme-linked immunosorbent assay (ELISA); Tiller FW et al.; A direct sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect Haemophilus influenzae type b capsular antigen . Using polystyrene as the solid phase and peroxidase-labelled rabbit antibody the assay detected the antigen in concentrations of 0.1 ng/ml . Linearity was achieved within the range of 1ng to 10 microgram/ml . Subtle measurements of Haemophilus influenzae type b capsular antigen in body fluids are possible through ELISA which is superior to counterimmunoelectrophoresis and latex-particle agglutination in this respect . ELISA should facilitate investigations concerning PRP pathogenic effects in experimental Hib infection as well as in human Hib disease. Mutat Res, 1981 Feb, 80(2), 239 - 48 Mutation induction in Haemophilus influenzae by ICR-191 . I . Development of a detection system for frameshift mutations; Perdue SW et al.; The investigation of mutagenic mechanisms in Haemophilus influenzae has been confined until now to mutagens that normally produce mainly base pair substitutions . This paper describes the development of a system suitable for detecting frameshift mutations induced by ICR-191 . The system involves reversions from thymidine dependence to thymidine independence . Evidence is presented from a comparison of the responses to ICR-191 and to N-methyl-N'-nitro-N-nitrosoguanidine that the system is specific for frameshift mutations . The genetic recombination involved in transformation leads to a marked increase in "spontaneous" reversion of the frameshift mutations but not of the base substitution mutations . Presumably, this is a consequence of mispairing, with consequent change in the number of bases, during the recombination. Postgrad Med J, 1981 Feb, 57(664), 117 - 9 Haemophilus endocarditis; Emmerson AM et al.; Two cases are presented of Haemophilus endocarditis in patients with presumed normal valves . One case was due to H . influenzae presenting as a typical case of infective endocarditis and the other was due to H . para-influenzae presenting as an acute pyrexia of unknown origin . The difficulties in making the diagnosis and the optimal treatment are discussed. Mutat Res, 1981 Feb, 80(2), 249 - 58 Mutation induction in Haemophilus influenzae by ICR-191 . II . Role of DNA replication and repair; Kimball RF et al.; Evidence is presented to show that presumptive frameshift mutations induced in Haemophilus influenzae by ICR-191 are fixed very rapidly, essentially at the time of treatment . DNA synthesis during treatment is essential for fixation, but DNA synthesis after treatment has no effect . The conclusion is drawn that the mutagen acts at the replication fork, possibly to stabilize misannealings arising in association with the discontinuities in the newly synthesized DNA . These results agree with earlier results on Escherichia coli showing that ICR-191 produces peak mutation frequencies in synchronized cultures at times when the replication fork has reached the locus being studied . They are in sharp contrast to the earlier results in H . influenzae with nitroso compounds and hydrazine that suggest these agents produce randomly distributed, reparable pre-mutational damage that still can be fixed (converted to final mutation) for some time after treatment when the replication fork reaches them . No evidence for such persistent pre-mutational lesions was found with ICR-191 . A defect in incision appeared to have very little influence on mutation induction by ICR-191 though it caused much more lethality . The interpretation of the mutation data was made somewhat uncertain, however, by an unexplained plating-density effect on the expression of the mutants in this strain . In contrast, incision deficiencies in E . coli and Salmonella typhimurium have been reported to cause a large increase in mutation induction and to allow lesions at some distance from the replication fork to produce mutations. South Med J, 1981 Feb, 74(2), 151 - 2, 156 Systemic Haemophilus influenzae infections in a community hospital: prevalence of ampicillin resistance; Schwartz RH et al.; Ampicillin-resistant strains are presently known to account for 10% to 20% of type b Haemophilus influenzae infections in the United States . To determine whether the incidence in a community hospital parallels that of several university hospitals, we reviewed medical records of the 99 children with type b Haemophilus systemic infections for the period 1976 to 1979 . These cass represented 1.8% of all pediatric medical admissions . In 1976-1977, 5% of those infections were caused by resistant strains; the incidence increased to 19% for the period 1978-1979 . This increase on a community hospital level parallels the increase in ampicillin resistance in Haemophilus noted in university hospitals and underscores the need for chloramphenicol (alone or in combination with ampicillin) as initial treatment for systemic Haemophilus infections. South Med J, 1981 Feb, 74(2), 147 - 50 Cefamandole failure in ampicillin-resistant Haemophilus influenzae b pneumonia; Markham RE et al.; A woman with rheumatoid arthritis and ampicillin-resistant Haemophilus influenzae type b (Hib) pneumonia complicated by bacteremia and empyema is reported . Initial therapy with cefamandole failed to eliminate bacteria from the pleural space and did not substantially affect the clinical course . However, cultures became negative and fever resolved when therapy was changed to chloramphenicol . Ampicillin-resistant Hib pneumonia in adults is an increasing problem and may be a difficult diagnosis to establish initially . Counterimmunoelectrophoresis may be useful in adults with pneumonia . If Hib antigen is detected, or if H influenzae is suspected on the basis of Gram stains and cultures, chloramphenicol should be given until the isolate is shown to be sensitive to ampicillin. J Bacteriol, 1981 Feb, 145(2), 1099 - 101 Plasmid transformation in Haemophilus influenzae; Albritton WL et al.; Purified 34-megadalton-plasmid deoxyribonucleic acid from antibiotic-resistant strains of Haemophilus influenzae transforms competent strains of H . influenzae more efficiently if the recipient strains contain certain other 30-megadalton plasmids. J Neurosurg, 1981 Feb, 54(2), 261 - 3 Haemophilus influenzae infections of cerebrospinal fluid shunts . Report of two cases; Lerman SJ; Two (1%) of 165 episodes of Haemophilus influenzae infection of the central nervous system occurred in patients with cerebrospinal fluid shunts . Both cases were caused by strains that could not yet be typed . The clinical presentation was similar to that of other forms of shunt infection, yet the pathogenesis may be similar to that of H . influenzae meningitis in children without shunts . Systemic antibiotic therapy, without shunt replacement or intraventricular antibiotic administration, may be more successful in shunt infections caused by H . influenzae than in those caused by other organisms. Clin Otolaryngol, 1981 Feb, 6(1), 5 - 13 Penicillin in acute otitis media: a double-blind placebo-controlled trial; Mygind N et al.; The effect of peroral penicillin-V (55 mg/kg/day in 7 days) on acute otitis media was studied in 149 children between the ages of 1 and 10 years in a double-blind, placebo-controlled investigation . The parameters of the disease employed were symptom scores for earache, fever and common cold, the use of analgetics, otoscopy, as well as tympanometry . The children were followed-up for 3 months . Penicillin had no effect on fever and common cold, but earache was significantly reduced on the 2nd day of treatment . The acute course of the disease was satisfactory in 69% of the children in the placebo group and in 86% in the penicillin group . In patients with pneumococci or haemolytic streptococci in the nasopharynx, the pain disappeared after 1-2 doses of penicillin, whereas the treatment had no effect in children with Haemophilus influenzae . There was no difference between the penicillin and the placebo groups with regard to the results of otoscopy and tympanometry after 1 week, 1 month and 3 months . No serious complications were observed . It is concluded that an attitude of "masterly inactivity" with regard to the treatment of acute otitis media is justifiable, provided sufficient analgesic treatment is given and also that the patient can be closely followed . As there are still many unanswered questions more controlled investigations are warranted. Tissue Antigens, 1981 Feb, 17(2), 205 - 11 Occurrence of HLA types in H . influenzae type B disease; Tejani A et al.; We have studied 50 Caucasoid children under 7 years of age with Haemophilus influenzae b disease . Half of the patients (Group A) had invasive disease shown by positive blood and/or spinal fluid culture . The other half (Group B) had noninvasive disease characterized by fever, nasopharyngitis, negative blood culture, and positive throat culture . Age, number of other siblings under 12 years old in the family, immune response, antibody production and genetic markers were compared in the two groups . Significant difference between the two groups was only seen in their genetic markers . HLA-B12 was present in 52% of Group A patients as opposed to 16% in Group B patients (P less than .01) . HLA-Bw40 was present in 24% of group B patients and absent in all Group A patients (P less than .01) . These findings would suggest that susceptibility and resistance towards developing invasive type b disease may be genetically determined. J Bacteriol, 1981 Feb, 145(2), 1075 - 8 Occurrence of pili on and adhesive properties of Haemophilus parainfluenzae; Kahn ME et al.; Of 20 clinical isolates of Haemophilus parainfluenzae, 13 produced a mannose-resistant hemagglutinin that agglutinated erythrocytes from chickens, horses, rabbits, and sheep . Examination with the electron microscope showed that only strain HR-885 was pilate . Grown in static liquid culture, the 12 hemagglutinating, nonpilate isolates formed small, tightly packed clumps, whereas strain HR-885 formed large, loosely packed clumps . However, seven isolates did not produce a hemagglutinin, did not clump, and were nonpilate. Carbohydr Res, 1981 Jan 15, 88(1), 85 - 92 Structural studies of the Haemophilus influenzae type e capsular polysaccharide; Tsui FP et al.; The structure of the Haemophilus influenzae type e capsular polysaccharide has been determined by a combination of chemical and spectroscopic methods . The structure of the repeating unit of the polymer was found to be leads to 3)-beta-D-GlcNAc-(1 leads to 4)-beta-D-ManANAc-(1 leads to ; both sugars were present in the pyranoid form. Carbohydr Res, 1981 Jan 15, 88(1), 77 - 84 Structural studies of two capsular polysaccharides elaborated by different strains of Haemophilus influenzae type e; Branefors-Helander P; The structures of two capsular polysaccharides elaborated by Haemophilus influenzae type e, strains NCTC 8455 and 8472, respectively, have been investigated, methylation analysis and n.m.r . spectrometry being the principal methods used . It is concluded that the polysaccharides are composed of repeating-units having the following structure: Formula: {See Text} . In the polysaccharide from strain NCTC 8472, all of the repeating-units contain the beta-D-fructofuranosyl group . The polysaccharide from strain NCTC 8455, however, contains only traces of D-fructose, corresponding to approximately one group per 100 repeating-units. Natl Inst Anim Health Q (Tokyo), 1981 Winter, 21(4), 159 - 62 Susceptibility of Haemophilus equigenitalis, the causal agent of contagious equine metritis, to 31 antimicrobial agents; Sugimoto C et al.; The minimal inhibitory concentrations of 31 antimicrobial agents were determined for 99 isolates of Haemophilus equigenitalis by the agar dilution method . All the isolates showed good susceptibility to 26 antimicrobial agents tests, minimal inhibitory concentrations of which were less than 3.13 micrograms/ml for more than 90% of the isolates . Of these agents, 4 macrolides (erythromycin, oleandomycin, kitasamycin, tylosin), 3 tetracyclines (tetracycline, chlortetracycline, oxytetracycline), 1 peptide (colistin), 1 penicillin (ampicillin) and 1 pleuromutilin (tiamulin) were the most active agents, showing a minimal inhibitory concentration of less than 0.39 micrograms/ml for more than 90% of the isolates . The growth of more than 90% of the isolates was not inhibited by 800 micrograms/ml of streptomycin. Natl Inst Anim Health Q (Tokyo), 1981 Fall, 21(3), 121 - 8 Glässer's disease in piglets produced by intraperitoneal inoculation with Haemophilus parasuis; Morozumi T et al.; Haemophilus parasuis was inoculated into the abdominal cavities of piglets . Its infective doses varied from 1.4 X 10(6) to 1.0 X 10(9) organisms . When inoculated with 1.0 X 10(9) or 1.6 X 10(8) organisms, piglets were affected with fibrinous polyserositis associated with arthritis and purulent meningitis . The three disorders were considered to be characteristic of Glasser's disease . Septicemia was also found in many of the infected piglets, some of which died within a few days after inoculation . No lesions were observed in piglets inoculated with 1.4 X 10(7) or 1.4 X 10(6) organisms . It was difficult to reisolate H.parasuis from lesions, especially those in the abdominal cavities of piglets killed on the 6th day after inoculation . Agglutinating and complement-fixing antibodies were present in the piglets with Glasser's syndrome examined on the 6th day after inoculation . Neither of them was detected in any piglet manifesting no clinical signs, except transient pyrexia. Scand J Infect Dis, 1981, 13(3), 177 - 83 The bacteriology of acute otitis media in children with special reference to Streptococcus pneumoniae as studied by bacteriological and antigen detection methods; Luotonen J et al.; The middle ear fluid (MEF) was studied during an acute attack of otitis media in 519 children, aged 3 months to 6 years . Streptococcus pneumoniae (Pn) was cultured from 39% of the cases; serotypes 19, 6, 3 and 23 were the most common . Haemophilus influenzae (Hi) was cultured in 12%; only 2/64 strains were of type b . Pn were found equally often in all age groups, but Hi were significantly less often isolated in children older than 3 years . The number of negative cultures increased with the age of the child . Pneumococcal capsular polysaccharide was detected with counterimmunoelectrophoresis and/or latex agglutination in 83% of the MEFs from which Pn were cultured, but also in about one third of the MEFs from which no bacteria could be grown . Altogether, with these methods combined Pn were implicated in nearly 60% of the cases of acute otitis media . Gram staining showed polymorphonuclear leucocytes in 85% of pneumococcal otitis cases that were verified by culture but also in 72% of the cases from which no bacteria could be cultured, supporting the contention that also these latter are usually caused by bacteria. Scand J Infect Dis, 1981, 13(2), 111 - 3 Branhamella catarrhalis and other bacteria in the nasopharynx of children with longstanding cough; Brorson JE et al.; Nasopharyngeal cultures from 180 children aged 1 to 9 were examined . All children were suffering from cough for at least 10 days . The findings were compared to those from 67 non-coughing children . Bordetella pertussis was isolated from 12.2% of the children in the study group but from none of the control children . Branhamella catarrhalis was isolated from 66.1% of the children in the study group and from 28.3% in the control group (p less than 0.01) . Br . catarrhalis was more common in pure cultures from sick children than from control children . Pneumococci were isolated from 20% of the sick children and 28% of the control children . Haemophilus influenzae was isolated from 15% in each group . Some possible interpretations of the findings are discussed. Can J Comp Med, 1981 Jan, 45(1), 2 - 7 Porcine Haemophilus pleuropneumonia epizootic in southwestern Ontario: clinical, microbiological, pathological and some epidemiological findings; Sanford SE et al.; A fibrinous necrotizing pleuropneumonia with a predominant mononuclear cell infiltrate commenced January 1978 . The pneumonia, caused by Haemophilus pleuropneumoniae assumed epizootic proportions and affected mainly feeder pigs in the intensive pig rearing area of southwestern Ontario . A few abortions occurred . Winter storms, recent transportation and other potentially stressful situations were associated with herd outbreaks . Broad spectrum antibiotics were usually effective in stopping deaths. Zentralbl Gynakol, 1981, 103(8), 434 - 7 {Studies into bacterial gynecological infections, with particular reference to anaerobic and micro-aerophile germs (author's transl)}; Muller H et al.; Reported in this paper are 50 pyogenic infections, with anaerobic germs being cultured in 40,7 per cent of the cases, as well as 105 examinations of patients with flour, with Haemophilus vaginalis having been isolated in 20 cases . Widespread occurrence of such pathogens and severity of infections caused by such bacteria call for close cooperation between clinical practitioners and microbiologists, as no safe diagnosis is practicable without involvement of the latter . Reference is made to possible therapies, using chloremphenicol and metronidazole. Chemotherapy, 1981, 27 Suppl 1, 93 - 9 Treatment of severe lower respiratory tract infections with ceftriaxone (Ro 13-9904) . A pilot study; Keller R et al.; Two pilot comparative trials in 29 patients suffering from severe lower respiratory tract infections are described . 15 patients received 7-10.5 g ceftriaxone as a total dose and 14 received 28 g amoxicillin, both antibiotics being given by intravenous route during 1 week . The local and systemic tolerance of the drugs were satisfactory; no adverse reactions or relevant laboratory changes were noticed . The clinical response was favourable in all patients . The mot relevant pathogens found in the sputum were Streptococcus pneumoniae in 11 cases and Haemophilus influenzae in 15 cases . Less relevant microorganisms such as Klebsiella pneumonia, Serratia, Pseudomonas sp . and Streptococcus viridans were cultivated prior to therapy . The two main pathogens disappeared from the sputum after therapy in 11 of 13 patients treated with ceftriaxone and in 10 of 13 treated with amoxicillin . The results of these pilot studies indicate that 7-10.5 g ceftriaxone are as active as 28 g amoxicillin in the treatment of severe lower respiratory tract infections. Arch Exp Veterinarmed, 1981, 35(3), 389 - 400 {Bacteriological diagnosis of Haemophilus pleuropneumonia in swine}; Kielstein P; Haemophilus pleuropneumonia (Matthews and Pattison, 1961; Shope, 1964) should now be accepted as the valid name of the pathogen of hemophilus pleuropneumoniae of swine, according to studies and the description by Kilian and co-workers (1978), while the name of Haemophilus parahaemolyticus should be considered a synonym . On top of Haemophilus pleuropneumoniae, Haemophilus parasuis and Haemophilus spec . "minor group" are also important to pneumonia, serositis, and arthritis (Glasser's disease) in swine, whereas Haemophilus suis is hardly any longer isolated . Evidence as to dependence on growth factors and to haemolysin activity is not sufficient in all cases for high-accuracy differentiation between those four haemophilus species . Such tests have to be supplemented with evidence as to separation of urea, xylose, lactose, and mannite or, in extraordinary cases, even with evidence to fermentation of melibiose and D-ribose, Serological typing is another tool for further differentiation . Pathologico-anatomic changes in terms of haemorrhagic-necrotising pleuropneumonia are caused by what is called Pasteurella haemolytica-like organism (Bertschinger and co-workers, 1978; Pohlenz and co-workers, 1978) rather than by haemophilic bacteria only . The authors, using the above pathogens, succeeded in causing in specific-pathogen-free pigs (SPF) manifest pleuropneumonia which could not be distinguished from haemophilus pleuropneumonia . Pathologically and bacteriologically, those germs are of great relevance to differential diagnosis, in the context of haemophilus pleuropneumonia. Ann Rech Vet, 1981, 12(3), 265 - 75 {A serological study of the contagious equine metritis: comparison between indirect immunofluorescence, slow agglutination and complement fixation techniques (author's transl)}; Tainturier D et al.; Serological response of pony mares to contagious equine metritis is studied comparing three techniques: slow agglutination, complement fixation and indirect immunofluorescence . Sera were taken from pony mares vaccinated with a heat inactivated suspension of Haemophilus equigenitalis, from experimentally-infected pony mares and from healthy horses . All three reactions detected antibodies in vaccinated and infected animals . The highest titers are observed with vaccinated mares . Titers are low in infected animals . Antibodies detected by indirect immunofluorescence appeared sooner and persisted longer in diseased animals than agglutinating or complement fixing antibodies . Only indirect immunofluorescence revealed a new contamination of two mares following coitus with a stallion excreting H . equigenitalis . Indirect immunofluorescence must be recommended in diagnosis of contagious equine metritis and in detection of chronic carriers. Infection, 1981, 9(5), 244 - 8 A combination of amoxicillin and clavulanic acid in the treatment of respiratory tract infections caused by amoxicillin-resistant haemophilus influenzae; Beeuwkes H et al.; This study was undertaken to evaluate the efficacy of a fixed combination of amoxicillin and clavulanic acid in 33 patients with chronic or recurrent respiratory tract infections (R.T.I.), mainly bronchitis . In two patients bronchopneumonia was diagnosed, and in one cystic fibrosis . The patients were treated with 750 mg of the drug combination (500 mg amoxicillin/250 mg clavulanic acid) t . i . d . for seven or ten days . Good clinical success was obtained in 17 patients and a clear improvement in another eight . The most frequently isolated micro-organism was Haemophilus influenzae; of the 22 strains isolated, 20 were resistant to 2 mg/l amoxicillin but sensitive to the combination of 2 mg/l amoxicillin and 1 mg/l clavulanic acid . Side-effects were reported in nine patients; two patients discontinued treatment for this reason . Amoxicillin/clavulanic acid is a useful therapeutic addition to the existing forms of treatment for amoxicillin-resistant respiratory tract infections. Zentralbl Bakteriol A, 1981, 249(2), 247 - 53 Evaluation of the beta lactam disk for rapid detection of penicillinase producing bacteria: comparison with three other methods; Qadri SM et al.; One thousand and four strains of gram positive and gram negative bacteria were tested for the production of beta lactamase by Beta Lactam reagent disks and the results were compared with acidometric microtiter, disk diffusion and antibiotic dilution procedures . Three hundred and sixty-three clinical isolates had a minimal inhibitory concentration (MIC) of greater than or equal to 2.0 micrograms/ml for penicillins . All the resistant strains of N . gonorrhoeae and Haemophilus tested gave positive beta lactamase reactions with both methods within 30 min . Four hundred and thirty-seven members of these two genera and all other bacteria with MIC values of less than or equal to 2.0 micrograms/ml remained negative for the beta lactamase test by both procedures in 4 h . The Beta Lactam reagent disk as well as the micro-method are simple, rapid and reliable . Cost analysis of the two procedures demonstrated the micro-method to be more economical. Chemotherapy, 1981, 27 Suppl 1, 37 - 41 Diffusion of ceftriaxone (Ro 13-9004/001) in the cerebrospinal fluid . Comparison with other beta-lactam antibiotics in dogs with healthy meninges and in dogs with experimental meningitis; Marchou B et al.; After i.v injection of 50 and 100 mg/kg ceftriaxone in 1 h in dogs with healthy meninges, the cerebrospinal fluid (CSF) concentrations found between minutes 90 and 240 were an average of 0.37 (0.32-0.41) and 1.22 microgram/ml (1.02-1.56), respectively . In dogs with meningitis a dosage of 50 mg/kg yielded high concentrations from minutes 60 to 240: on average, 13.0 microgram/ml (9.9-14.9); 9.9 microgram/ml in the fourth hour . The concentrations obtained in dogs with healthy meninges were 10-100 times higher than the MICs for meningococci and Haemophilus influenzae . In the infected dogs, the concentrations obtained were enough to eliminate virtually all the bacteria responsible for meningitis (except Mycobacterium tuberculosis) . In the dogs with healthy meninges, the ratio of the CSF/plasma AUCs was 0.61% after 50 mg/kg, and 1.00% after 100 mg/kg . In the infected dogs, this ratio was 22.4% after 50 mg/kg . Comparison of the ratio of AUCs obtained under ceftriaxone with that under other beta-lactam antibiotics shows the former to be one of the highest. Am J Hosp Pharm, 1981 Jan, 38(1), 54 - 8 Evaluation of cefaclor; Derry JE; The chemistry, pharmacology, pharmacokinetics, bacterial spectrum, clinical use, dosage, adverse reactions, and dosage forms and cost of cefaclor are reviewed . Cefaclor, a congener of cephalexin monohydrate, is a new semisynthetic cephalosporin antibiotic . It is well absorbed when given orally on an empty stomach; absorption is delayed by the presence of food . Although metabolism may play a role in the disposition of cefaclor, elimination is primarily renal . Cefaclor's spectrum of activity is similar to that of cefalexin, including a wide range of gram-negative and gram-positive bacteria; in particular, Escherichia coli, Klebsiella spp., Proteus mirabilis, Salmonella spp., and Haemophilus influenzae are more susceptible to clinically achievable concentrations of cefaclor than cephalexin . Cefaclor has been demonstrated to be effective against beta-lactamase-producing H . influenzae resistant to ampicillin, but further studies are needed to establish the clinical significance of this activity . Efficacy of cefaclor has been demonstrated in urinary tract, upper and lower respiratory tract, and skin and soft tissue infections in adults and children as well as in pediatric otitis media . Adverse reactions, mostly gastrointestinal, are generally mild and occur in few patients . Usual doses are 250-500 mg every eight hours in adults and 20--40 mg/kg/day in children, although this pediatric dose may be two low for otitis media . Clinical superiority of cefaclor over less expensive antibiotics has not been demonstrated. J Clin Microbiol, 1981 Jan, 13(1), 224 - 5 Iodometric spot test for detection of beta-lactamase in Haemophilus influenzae; Lee WS et al.; A simple iodometric spot test for detecting beta-lactamase activity in Haemophilus influenzae was compared with the capillary procedure for detecting beta-lactamase and the Bauer-Kirby disk susceptibility procedure . Isolates were classified similarly by all three procedures. Scand J Infect Dis, 1981, 13(2), 155 - 7 Neonatal meningitis caused by Haemophilus influenzae type c; Berg U et al.; Haemophilus influenzae type c was isolated from blood and cerebrospinal fluid in a 3-day-old fullterm boy with clinical signs of serious infection . Ampicillin, cloxacillin and gentamicin were instituted initially . After 3 days of therapy the child developed a hemiparesis . Treatment was changed to chloramphenicol and the baby improved . The implications of H . influenzae serotype c as a possible pathogen, early diagnostic procedures and therapeutic problems are discussed. Bol Med Hosp Infant Mex, 1981 Jan-Feb, 38(1), 79 - 86 {Haemophilus influenzae sensitivity to ampicillin and chloramphenicol in children in Mexico City}; Trejo y Perez JA et al.; The sensitivity to chloramphenicol and ampicillin of 127 strains of H . influenzae was tested . One hundred and one strains were obtained from the pharyngeal exudate of 828 healthy carriers under 5 years of age and 26 from the spinal fluid of children with meningoencephalitis . Sixty per cent of isolations corresponded to type b; 40 per cent were non typical and we only identified one type e . All H . influenzae obtained from spinal fluid corresponded to type b . The frequency of healthy carriers was greater in intrafamily contacts of children with H . influenza meningoencephalitis (p less than 0.01) . Percentages of resistance to ampicillin varied between 6 and 23% for the different groups; we found no statistical difference among them (p less than 0.2) . The prevalence of H . influenza resistant to ampicillin in the population studied was 1.2% for type b strains and 0.2% for non typical bacteria . Fourteen per cent of penicillin resistant type b strains were identified; all 127 isolations were to chloramphenicol; therefore, we recommend this drug instead of ampicillin for the treatment of H . influenza infections, with the exception of acute otitis media. J Immunol Methods, 1981, 43(1), 35 - 47 A radioactive antigen-binding assay for the measurement of antibody to Haemophilus influenzae type b capsular polysaccharide; Kuo JS et al.; A new polyethylene glycol (PEG) radioimmunoprecipitation assay was developed for the detection of antibody to Haemophilus influenzae b capsular polysaccharide, polyribosylribitol phosphate (PRP) . The radioactive antigen, {3H}PRP, with a high specific activity, was produced by growing the organism in the presence of {3H}ribose and was purified by hydroxylapatite and Sepharose 4B column chromatography . In the assay, PEG (12.5%) was used to separate antibody-bound {3H}PRP from free {3H}PRP . The assay covered the range of 0.5 and 20 ng antibody/assay at a maximum sensitivity of 0.5 approximately 1.0 ng antibody/assay . With various dilutions (1-20 ng antibody/assay) of S . Klein reference antiserum, the within-run coefficient of variation (CV) of 10 replicates ranged from 3.5 to 8.5% . Average CVs of 8.9% and 11.0% were obtained in the between-run and day-to-day reproducibility studies . The binding of {3H}PRP to S . Klein reference antiserum was severely inhibited by a minute amount of non-radioactive PRP; however, no significant interference was found in the presence of high concentrations of polysaccharides from Escherichia coli K100 and Streptococcus pneumoniae indicating that the RIA was highly specific for antibody to H . influenzae b PRP . The present RIA is a simple, specific, sensitive and reproducible procedure for the evaluation of antibody responses of young animals and infants to H . influenzae b vaccines and infections. J Hyg Epidemiol Microbiol Immunol, 1981, 25(1), 17 - 23 Serotyping of Haemophilus influenzae a comparison of co-agglutination with countercurrent--immunoelectrophoresis and slide--agglutination; Tiller FW; 30 out of 55 strains of H . influenzae could be assigned to one of the six serotypes A--F by slide agglutination, countercurrent-immunoelectrophoresis or co-agglutination . While slide-agglutination appeared less reliable due to non-specific agglutinations countercurrent-immunoelectrophoresis was of high specificity . No cross reactions were encountered in this test and results were unambiguously to evaluate . Co-agglutination is attractive because of its rapidity and simplicity without any need of special equipment . It was found to be of increased sensitivity in detecting type B capsular antigen when compared with countercurrent-immunoelectrophoresis, the problem of cross-reactions remains to be solved however . The use of co-agglutination for serotyping H . influenzae strains in combination with countercurrent-immunoelectrophoresis can be recommended. Clin Radiol, 1981 Jan, 32(1), 99 - 105 Pneumatocoeles following Haemophilus influenzae pneumonia; Warner JO et al.; Two children are reported who developed lung radiolucencies identical to staphylococcal pneumatocoeles after haemophilus influenzae pneumonia . Recognition that such translucencies can occur after various bacterial pneumonias is important . The radiographic appearances can be confused with congenital lung cysts, which could result in unnecessary surgery . There has been a recent increased incidence of reports of H . influenzae pneumonia in children, with lobar involvement predominating . Thus H . influenzae must be considered a significant cause of lobar pneumonia and the presence of pneumatocoeles does not preclude the diagnosis. J Bacteriol, 1981 Jan, 145(1), 596 - 604 Isolation and partial characterization of outer and inner membranes from encapsulated Haemophilus influenzae type b; Loeb MR et al.; A method has been developed to separate the cell envelope of encapsulated (type b) Haemophilus influenzae into its outer and inner membrane components with procedures that avoided two problems encountered in fractionation of this envelope: (i) the tendency of the outer and inner membranes to hybridize and (ii) the tendency of the apparently fragile inner membrane to fragment into difficulty sedimentable units . Log phage cells, whose lipids were radioactively labeled, were lysed by passage through a French press . The lysate was applied to a discontinuous sucrose gradient, and envelope-rich material was collected by centrifugation onto a cushion of dense sucrose under carefully controlled conditions . This material was then further fractionated by isopycnic centrifugation in a sucrose gradient to yield four membrane fractions which were partially characterized . On the basis of their radioactivity, buoyant density, ultrastructure, polypeptide composition, and content of phospholipid, protein, lipopolysaccharide, and succinic dehydrogenase, these fractions were identified as follows: fraction 1, outer membrane vesicles with very little inner membrane contamination (less than 4%); fraction 2, outer membrane vesicles containing entrapped inner membrane; fraction 3, a protein-rich fraction of inner membrane; fraction 4, a protein-poor fraction of inner membrane . Fractions 3 and 4 contained about 25% outer membrane contamination. Scand J Infect Dis, 1981, 13(2), 105 - 9 Epidemiology of Neisseria meningitidis; prevalence and symptoms from the upper respiratory tract in family members to patients with meningococcal disease; Olcen P et al.; The prevalence of Neisseria meningitidis during endemic conditions was studied in 2 groups of people: (1) 64 family members to patients with meningococcal disease, and (2) 64 family members to patients with meningitis due to Haemophilus influenzae or Streptococcus pneumoniae . In group 1 the carrier rate of meningococci of the same serogroup, sensitivity to sulphonamide, and serotype (group B) as the index strain was 34% . The carrier rate of meningococci group A, B, C and Y was 39% in group 1 and 1.6% in group 2 . The 25 times higher carrier rate in group 1 gives some explanation of the increased risk for family members to patients with meningococcal disease . This risk was calculated to have been 3,000-4,000 times higher for the family members during one month after the diagnosis of an index case 1965-1977 in our county . The hypothesis that meningococci as a rule are introduced into a family by an adult and then spread within the family to a child finds no support in the present study . A statistically highly significant association was found between carriage of pathogenic meningococci and symptoms from the upper respiratory tract. J Infect Dis, 1981 Jan, 143(1), 32 - 41 Antibody response to capsular polysaccharides of groups A and C neisseria meningitidis and Haemophilus influenzae type b during bacteremic disease; Kayhty H et al.; Levels of antibodies to the capsular polysaccharides of groups A and C Neisseria meningitidis and Haemophilus influenzae type b were determined by radioimmunoassay in acute- and convalescent-phase sera of 377 patients with meningitis, septicemia, or epiglottitis . Diagnostic criteria, based on a fourfold or greater rise in antibody level and/or a high specific antibody level, correctly identified 85% of group A meningococcal diseases, 90% of group C meningococcal diseases, and 78% of H . influenzae type b diseases in children older than but only 15% in infants younger than 1.5 years of age . When levels of antibody in acute-phase sera were high, they were predominantly of the IgA class . A greater than fourfold rise in levels of antibodies to group A meningococcus was seen in 10%-32% of persons with disease caused by other bacteria, but minimal false-positive reactions occurred with group C meningococcus or H . influenzae type b. Drugs, 1981, 22 Suppl 1, 96 - 9 Cefoperazone in lower respiratory tract infections; Woods CJ et al.; 17 hospitalised patients with a wide variety of common lower respiratory tract infections received at least 6 days of intravenous bolus cefoperazone 1.0g 12-hourly . Disease was caused by Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and mixed anaerobes in 1 patient . All isolates were sensitive to cefoperazone . 11 patients were cured, 4 improved, and 2 failed (1 of whom had an anaerobic empyema) . Toxicity and side effects were infrequent . In general cefoperazone was effective therapy for these infections. Antimicrob Agents Chemother, 1981 Jan, 19(1), 101 - 5 Limited in vitro activity of cefamandole against 100 beta-lactamase- and non-beta-lactamase-producing Haemophilus influenzae strains: comparison of moxalactam, chloramphenicol, and ampicillin; Bergeron MG et al.; In the present study, the minimal inhibitory concentrations and minimal bactericidal concentrations of moxalactam, cefamandole lithium, ampicillin, and chloramphenicol were determined, both in broth and on solid medium, against 75 non-beta-lactamase-producing and 25 beta-lactamase-producing strains of Haemophilus influenzae . Most of the 75 strains were inhibited or killed by 2 microgram or less of ampicillin, chloramphenicol, or moxalactam per ml, but cefamandole exhibited poor bactericidal activity against 11 non-beta-lactamase-producing strains, of which 9 were non-type B H . influenzae . Most of the 25 beta-lactamase-producing H . influenzae were resistant to 128 microgram of ampicillin per ml . Both moxalactam and chloramphenicol, which had minimal inhibitory concentrations of less than 0.25 and 2 microgram/ml, respectively, were more active than cefamandole, which had a minimal inhibitory concentration ranging from 2 to greater than or equal to 128 microgram/ml. J Immunol Methods, 1981, 43(2), 209 - 18 Staphylococcal protein A-enzyme immunoglobulin conjugates: versatile tools for enzyme immunoassays; Yolken RH et al.; This report describes the use of peroxidase-labeled staphylococcal protein A to prepare conjugates suitable for direct enzyme immunoassays (EIAs) . Such conjugates were used to develop direct EIA systems for the measurement of two antigens associated with human infections, human rotavirus and Haemophilus influenzae type b polysaccharide . Both systems were as sensitive or more sensitive than currently available EIAs for the measurement of standard antigens . In addition, both systems could be utilized to correctly identify the antigens in clinical specimens obtained from sick patients . Efficient enzyme conjugates prepared with enzyme-labeled staphylococcal protein A were simple to formulate providing that immunoglobulin of the appropriate animal species was available as the source of antibody . The use of such conjugates might increase the availability of practical EIA systems for the measurement of a wide range of medically important antigens. Curr Med Res Opin, 1981, 7(7), 429 - 39 Bactericidal activity of erythromycin in the respiratory system; Fraschini F et al.; In vivo and in vitro studies were carried out to assess tha levels in bronchial mucus of ampicillin, amoxycillin, bacampicillin, cefotaxime and erythromycin, and to compare their minimum bactericidal concentrations and killing rate against hospital strains of Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae . Both the percentage ratios of serum/mucus concentration peaks and of serum/mucus area under the concentration time curve values were higher for erythromycin than for the other antibiotics . Determination of the minimum bactericidal concentrations showed that the bacterial strains were sensitive to small quantities of erythromycin, and the time necessary to sterilize inocula varied from 4 to 16 hours. Am J Vet Res, 1980 Dec, 41(12), 2114 - 8 Purification and properties of Haemophilus paragallinarum hemagglutinin; Iritani Y et al.; Hemagglutinin (HA) of Haemophilus paragallinarum was purified, and its immunologic, chemical, and morphologic properties were studied . The HA was purified by gel filtration on Sepharose 6B and by subsequent ultracentrifugation of trypsinized cells after pretreatment with neuraminidase . After gel filtration, the HA component (fractioned HA) gave 1 precipitin line by gel diffusion, and after inoculation in chickens, hemagglutinination-inhibition antibody to trypsin-sensitive HA antigen was found . Chickens inoculated with the fractionated HA were protected from challenge exposure with H paragallinarum . In a sample further purified by ultracentrifugation (purified HA), a single protein band was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; it had a molecular weight of approximately 39,000 . A molecular weight of several hundred thousand to several million was observed by gel filtration . Seemingly, HA of H paragallinarum is an aggregate of more than 20 HA sub-units . The purified HA included protein and some sugars, and according to electron microscopic observation, had a filamentous structure. Antimicrob Agents Chemother, 1980 Dec, 18(6), 841 - 3 In vitro susceptibility of Haemophilus equigenitalis, the causative organism of contagious equine metritis 1977, to antimicrobial agents; Dabernat HJ et al.; The in vitro susceptibility of recent clinical isolates of Haemophilus equigenitalis to various antimicrobial agents was determined by the disk diffusion test and the World Health Organization-International Collaborative Study agar dilution procedure . Ampicillin and tetracycline were the most active drugs . All strains were susceptible to beta-lactam antibiotics, chloramphenicol, trimethoprim-sulfamethoxazole, nalidixic acid, nitrofurantoin (Furadantin), and bacitracin . All but two strains were resistant to streptomycin, whereas all strains were susceptible to the other aminocyclitol antibodies . All strains were resistant to clindamycin, lincomycin, and metronidazole. P N G Med J, 1980 Dec, 23(4), 174 - 8 Primary gram negative pneumonia in adults in Papua New Guinea; Lee L et al.; A retrospective review of gram-negative bacteraemia in Papua New Guinean adults revealed four cases of primary gram negative pneumonia over a two-year period . Patients with primary gram negative pneumonia constituted less than 1% of all pneumonias admitted to the medical ward . Pseudomonas pseudomallei, Haemophilus influenzae and Klebsiella pneumoniae were the aetiologic agents . Three of four patients died following a fulminant course . It is concluded that primary gram-negative pneumonia in Papua New Guinea is rare but carries a high mortality. Antimicrob Agents Chemother, 1980 Dec, 18(6), 844 - 52 Comparison of sensititre dried microtitration trays with a standard agar method for determination of minimum inhibitory concentrations of antimicrobial agents; Reeves DS et al.; A total of 222 clinical isolates were used to test the accuracy of Sensititre dried microtitration trays for determining minimum inhibitory concentrations (MICs) of antimicrobial agents . In comparison with an agar dilution technique, 89.5% of all the pairs of results were within one doubling dilution . The 2,420 pairs of MIC results with finite values gave a corresponding figure of 86.8% . Exclusion of sulfisoxazole results, which demonstrated a significant interlaboratory variation in accuracy, raised this value to 89.1% . Very good differentiation of beta-lactamase-producing strains of Staphylococcus aureus (24 of 24 giving an MIC greater than or equal to 0.25 micrograms/ml) and Haemophilus influenzae (3 of 3 giving an MIC greater than or equal to 32 micrograms/ml) was obtained with the Sensititre system . This method also clearly distinguished erythromycin-resistant S . aureus strains (7 of 7 giving an MIC greater than 32 micrograms/ml) from the susceptible strains (26 of 28 giving an MIC less than or equal to 0.5 microgram/ml plus 1 strain at 1.0 microgram/ml and 1 at 2.0 micrograms/ml) . Sensititre offers an accurate and convenient method of determining MICs comparable to those obtained with the agar dilution procedure, with the advantage of an extended shelf life when stored at room temperature. Allergy, 1980 Dec, 35(8), 665 - 9 IgE antibodies to bacteria in patients with bronchial asthma; Pauwels R et al.; Bacterial respiratory infections, especially with Haemophilus influenzae and Streptococcus pneumoniae, are frequently associated with an increase of airways obstruction in patients with bronchial asthma . The possible involvement of immediate hypersensitivity in this phenomenon was studied . IgE antibodies to Haemophilus influenzae (HI) and Streptococcus pneumoniae (SPn) were investigated in the serum of 190 adult patients with bronchial asthma . The IgE antibodies were measured using a solid phase radioimmunoassay method . Living bacteria were used as solid phase . A correction of the non-specific binding of IgE was necessary . IgE antibodies to one or both bacteria were present in 55 of the 190 patients (29%) . Eighteen patients were sensitive to HI, 33 to SPn and four to both bacteria . Significantly more IgE antibodies to bacteria were found in patients with demonstrable IgE antibodies to various inhalant allergens . However, the IgE antibodies to one or both bacteria were also present in 22% of patients with no other demonstrable IgE mediated hypersensitivity . The total serum IgE level in patients with IgE antibodies to bacteria was not significantly higher than in patients without hypersensitivity to these bacteria . From these data we concluded that immediate hypersensitivity to bacteria may play a role in the infectious exacerbations of bronchial asthma. Clin Exp Immunol, 1980 Dec, 42(3), 530 - 4 Formalin-treated bacteria as selective B cell mitogens in the study of lymphocytes from patients with hypogammaglobulinaemia; Banck G et al.; Staphylococcus aureus strain Cowan I, Haemophilus influenzae, and Branhamella catarrhalis that stimulate human B lymphocytes, but not T lymphocytes, were used to study the B lymphocyte function in patients with hypogammaglobulinaemia . Lymphocytes from two patients with no circulating B cells were not stimulated to increased DNA synthesis by these bacterial mitogens . The lymphocytes of six patients with hypogammaglobulinaemia and normal numbers of circulating B cells responded to the bacterial mitogens but in five patients the response was decreased in comparison with healthy controls. J Pharmacol Exp Ther, 1980 Dec, 215(3), 691 - 6 Effects of vaccination with Haemophilus influenzae on adrenoceptor function of tracheal and parenchymal strips; Schreurs AJ et al.; Haemophilus influenzae is a bacterium that can be isolated from the deeper airways of asthmatic patients . We investigated the effect of vaccination with H . influenzae on alpha and beta adrenoceptor function in guinea-pig tracheal spirals and lung parenchymal strips . The tracheal spirals from H . influenzae-vaccina