Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis.

The frequency of colonization and intracellular localization of nontypeable Haemophilus influenzae (NTHi) in the lower respiratory tract was determined in healthy adults and in clinically stable and acutely ill chronic bronchitis (CB) patients. NTHi was recovered from bronchial wash or bronchial brush specimens in 6 of 23 (26%) stable CB patients and in 1 of 15 (7%) CB patients with a respiratory exacerbation. No NTHi (0 of 26) was recovered from lower tract specimens of healthy adults undergoing anesthesia for elective surgery. Molecular typing of NTHi strains revealed that five of nine patients with stable CB had different strains in upper respiratory tract and bronchial wash/brush specimens collected simultaneously. Four stable patients with CB had different strains recovered on repeat bronchoscopy. These results demonstrate the frequent colonization of the lower airways of stable CB patients with multiple strains of NTHi. Bronchial biopsies also were examined for intracellular NTHi by in situ hybridization and immunofluorescence microscopy. Intracellular NTHi were found in 0 of 7 healthy adults, 8 of 24 patients with clinically stable CB, and 13 of 15 acutely ill CB patients. This observation suggests a role for intracellular infection by NTHi in the pathogenesis of exacerbations of CB.     

Hemophilus influenzae biotypes and chronic bronchitis

Hemophilus influenzae can be differentiated into 6 biotypes on the basis of 3 biochemical reactions. This study was undertaken to determine the biotypes of respiratory isolates from an adult population with chronic bronchitis and to compare the biotypes of upper and lower respiratory tract isolates of individual patients. For rapid biotyping of serologically nontypable H. influenzae, we used 2 commercially prepared kits (Minitek and IDS RapID Systems). Twenty-three of 29 isolates (79%) had biochemical characteristics of biotype II with the Minitek system. Eighteen of the same 29 isolates were retested with the IDS RapID System and reacted as biotype II organisms. Seven of 9 and 4 of 4 paired transtracheal/oropharyngeal samples had identical biotypes when tested with the Minitek and IDS RapID System, respectively. These findings suggest that H. influenzae organisms are exchanged between the oropharynx and tracheobronchial tree of elderly male patients with chronic bronchitis.     

Reduction in the incidence of acute bronchitis by an oral Haemophilus influenzae vaccine in patients with chronic bronchitis in the highlands of Papua New Guinea

Following the administration of a standardized questionnaire, 62 adult patients with chronic bronchitis were enrolled into a double-blind controlled trial of an oral killed Haemophilus influenzae vaccine in the highlands of Papua New Guinea. A 3-day course of vaccine or placebo was given monthly for 3 consecutive months. Participants were monitored weekly over 12 months for acute exacerbations; early morning sputum specimens were collected monthly and during acute exacerbations. Density of colonization by H. influenzae and H. parainfluenzae was determined by standard quantitative and semiquantitative techniques, and the latter method (quadrant score) was used to determine the density of growth of pneumococci. A total of 30 patients received vaccine and 32 placebo. The incidence rate of acute bronchitis in the vaccine group (0.011 episodes/person-weeks) was significantly lower than that in the placebo group (0.021 episodes/person-weeks), but there was no difference between the two groups in the incidence rates of more severe disease. Vaccine efficacy was maximal at times of peak incidence of disease. There was no evidence of a decline in vaccine efficacy for acute bronchitis over the 12-month follow-up period. The number of viable H. influenzae in the sputum declined in both vaccine and placebo groups over the 12-month follow-up period. The average concentration of H. influenzae in the vaccine group fell below that in the placebo group within 1 to 2 months after first immunization and remained so for 12 months, although the difference between the two groups narrowed during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease

Nontypeable Haemophilus influenzae colonizes the respiratory tract of adults with chronic obstructive pulmonary disease (COPD) and causes intermittent exacerbations. Isolates of H. influenzae collected monthly in a prospective study were subjected to molecular typing. During a 7-year study spanning 345 patient-months of observation, 122 episodes of negative cultures lasting 1 month or more, and that were preceded and followed by isolation of an apparently identical strain of H. influenzae, were found. Seventeen such episodes of negative cultures, lasting 6 months or more and spanning 203 patient-months, were studied in detail to test the hypothesis that these periods of negative cultures represented continuous colonization by the same strain of H. influenzae. Molecular typing by three independent methods established that the strains preceding and following the episodes of negative cultures were indeed identical. Strain-specific H. influenzae DNA was detected in some of the sputum samples that had yielded negative cultures. These results indicate that some patients with COPD are persistently colonized with H. influenzae and that sputum cultures underestimate the frequency of colonization of the respiratory tract by H. influenzae in COPD. This observation has a significant impact on understanding bacterial colonization in COPD.     

Strain-specific immune response to Haemophilus influenzae in chronic obstructive pulmonary disease

Previous studies of immune response to Haemophilus influenzae after exacerbations of chronic obstructive pulmonary disease (COPD) have yielded contradictory results. Using homologous (infecting) strains and immunoassays to surface-exposed epitopes, we tested the hypothesis that adults with COPD make new antibodies to strain-specific, surface-exposed epitopes on H. influenzae after exacerbations. We collected clinical information, sputum, and serum monthly and during exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H. influenzae after exacerbations associated with H. influenzae in sputum were detected with whole bacterial cell ELISA and bactericidal assays. An immune response to homologous H. influenzae occurred after 22 of 36 (61.1%) exacerbations with newly acquired strains compared with 7 of 33 (21.2%) exacerbations with preexisting strains (odds ratio [OR] = 4.4; 95%, 1.8 to 10.8; p = 0.001). An absence of an immune response was strongly associated with complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p = 0.001). New bactericidal antibodies developed after exacerbations were highly strain specific, showing bactericidal activity for only 11 of 90 (12.2%) heterologous strains. Development of an immune response to H. influenzae supports its role in causing exacerbations. The strain specificity of the immune response likely represents a mechanism of recurrent exacerbations.     

Antimicrobial resistance of Haemophilus species in patients with chronic bronchitis.

Haemophilus influenzae strains resistant to ampicillin have become an important cause of disease in pediatric patients. Because many adults with chronic bronchitis carry Haemophilus organisms in their tracheobronchial tree and because antimicrobial agents are used commonly in these patients, we assessed the prevalence of resistance to ampicillin and other antimicrobial agents in this population. We studied 150 Haemophilus isolates (73 H. influenzae, 69 H. parainfluenzae, 6 H. parahemolyticus, and 2 H. hemolyticus) obtained from 138 patients with chronic bronchitis from January 1978 through March 1979. Ampicillin resistance due to production of beta-lactamase was found in 7 of the 150 isolates (4.7 %)-2 H. influenzae, 4 H. parainfluenzae and 1 H. parahemolyticus. Resistance to tetracycline was found in 9 strains (6 %), but all strains were susceptible to chloramphenicol.     

Haemophilus influenzae tenosynovitis.

A case is reported of polytenosynovitis in a 31-year-old male during the course of a severe bacteraemic illness caused by Haemophilus influenzae type b. The clinical presentation was similar to tenosynovitis caused by bacterial or viral agents. As the management of the H. influenzae tenosynovitis would differ from that due to other causes, the addition of H. influenzae type b to a differential of tenosynovitis should be considered. Recognition and prompt treatment by appropriate antibiotics may be important to avoid suppurative complications affecting the tendons. As the pathophysiology of the tenosynovitis is not clear, careful bacteriological and immunological assessment must be obtained.     

Bacteraemic Haemophilus influenzae pneumonia

Bacteraemia with Haemophilus pneumonia is uncommon. To determine its incidence and features case notes of patients in whom Haemophilus spp. were isolated from blood and pleural fluid over a five-year period were reviewed. Eight adult patients with H. influenzae bacteraemia were identified, five of whom had pneumonia on clinical and radiographic criteria. Only one patient had a predisposing factor, chronic obstructive lung disease. Two patients had beta-lactamase producing isolates, one of whom developed an empyema, following treatment with ampicillin, which required surgical drainage. Four patients were elderly, aged 69-80 yrs and were clinically in shock at the time of diagnosis. Seven of the eight patients survived.     

Fatal Haemophilus influenzae endocarditis

The range of microorganisms that may cause bacterial endocarditis is extensive. Increasingly recognised is the frequency with which Haemophilus species may be associated with this condition, although they account for less than 1% of cases. Haemophilus influenze, however, is very rarely implicated. We report a fatal case of H. influenzae endocarditis in a 55-year-old man.     

Invasive Haemophilus influenzae disease in adults

In a five-year period, 29 cases of bacteremia and/or meningitis in adults caused by Haemophilus influenzae were seen in our large community hospital. There were 17 cases of bacteremic pneumonia and 12 cases of serious extrapulmonary infections. The extrapulmonary infections included cases of endocarditis, meningitis, cholecystitis, epiglottitis, tubo-ovarian abscess, and cellulitis. In contrast with the pediatric experience, H influenzae type B was the causative pathogen in only 45% of patients and only one isolate was ampicillin resistant.     

Resistance to trimethoprim in Haemophilus influenzae

Summary The mechanisms of resistance to trimethoprim in eleven U.K. clinical isolates ofHaemophilus influenzae were studied. The levels of dihydrofolate reductase (DHFR) activities in crude extracts from four resistant wild-types were similar to those in susceptible controls. However, activities in extracts from the other seven resistant wild-type isolates, and transformants of two of these, were at least triple those in the sensititive strains. Resistance to trimethoprim was also selected forin vitro during prolonged exposure to the drug and was associated with increased levels of DHFR specific activity in the mutants. DHFR enzymes were, however, still very susceptible to inhibition by trimethoprim. Activities in four extracts, including one from a transformant of a resistant mutant, were reduced by at least 45% following incubation with 10^–8 M trimethoprim. The results suggested that overproduction of the chromosomal DHFR enzyme may be the resistance mechanism in some organisms. The much lower DHFR activities measured in extracts from other resistant isolates may reflect synthesis of chromosomal enzymes that have reduced susceptibility to trimethoprim.

---

Trimethoprim-Resistenz bei Haemophilus influenzae

Zusammenfassung Resistenzmechanismen gegen Trimethoprim wurden bei 11 britischen Isolaten vonHaemophilus influenzae untersucht. Die Dihydrofolat-Reduktase-Aktivitäten in ungereinigten Extrakten aus vier resistenten Wildtyp-Stämmen waren mit denen empfindlicher Kontrollen vergleichbar. Dagegen waren die Enzymaktivitäten in den Extrakten aus den anderen sieben Wildtyp-Isolaten und aus Transformanten zwei dieser Stämme mindestens dreimal so hoch wie bei empfindlichen Stämmen. Gegen Trimethoprim resistente Stämme wurdenin vitro bei längerer Exposition gegenüber der Substanz selektiert. Die Resistenz der Mutanten war mit erhöhter Dihydrofolat-Reduktase-Aktivität assoziiert. Dennoch waren die Dihydrofolat-Reduktasen jeweils sehr gut durch Trimethoprim hemmbar. Nach Inkubation mit 10^–8M Trimethoprim wurden die Enzymaktivitäten in den vier Extrakten einschließlich dem Extrakt aus dem Transformanten einer resistenten Mutante um mindestens 45% reduziert. Nach diesen Ergebnissen ist möglicherweise die Überproduktion des chromosomal kodierten Enzyms Dihydrofolat-Reduktase bei einigen Stämmen für die Resistenz verantwortlich. Die sehr viel niedrigeren Dihydrofolat-Reduktase-Aktivitäten in Extrakten anderer resistenter Isolate könnten darauf beruhen, daß in diesen Stämmen chromosomal kodierte Enzyme mit verminderter Empfindlichkeit gegenüber Trimethoprim gebildet werden.