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Hemophilus influenzae type B is known for its predilection to produce infections in the cheeks of infants. Early recognition and aggressive intervention are essential to avoid potentially life-threatening sequelae. A case is presented in which a resistant strain obscured the diagnosis and prolonged the illness. Clinical manifestations and differential diagnosis of the disease are discussed.
Hemophilus influenzae may account for 10% or more of cases of acute hematogenous osteomyelitis in infants. H. influenzae osteomyelitis is more often seen in the upper extremities. Two patients with H. influenzae acute osteomyelitis seen at a community hospital are described. The second patient is the first known case of osteomyelitis secondary to ampicillin-resistant H. influenzae. A review of 22 additional cases revealed that meningitis accompanied osteomyelitis in 10% (2/22).
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Influenza C virus, J.J. strain, is readily propagated following intra-amniotic inoculation of embryonated eggs on the 14th day of incubation. The resulting infection is inapparent in that there is no obvious interference with normal embryonic development and no evidences of injury can be detected by the light microscope. Hemophilus influenzae, type b thrives luxuriantly in the amniotic fluid of embryonated eggs inoculated by the intra-amniotic route on the 15th day of incubation. The effects of the establishment of the bacterial infection in the embryo are noted by the occurrence of death, bacteriemia or characteristic inflammatory lesions in the form of purulent sinusitis, pharyngitis, tracheo-bronchitis and meningo-encephalitis. These lesions may occur singly or in various combinations. The incidence and severity of disease manifestations in infected embryos depends on the proportion of encapsulated and virulent bacilli in the inoculum, the number of infectious doses and the growth rate of the bacteria in the surrounding amniotic fluid. Combined viral and bacterial infection established by intra-amniotic inoculation with influenza C virus on the 14th followed by Hemophilus influenzae, type b on the 15th incubation day brings about a significant increase in the incidence and severity of disease manifestations in the embryos. Selective survival and marked acceleration of the growth rate of encapsulated and virulent elements of the bacterial population is promoted in the virus-infected embryos. The disease process appears to be entirely attributable to the bacterial component. There seems to be relatively little or no effect on influenza C virus by the accompanying proliferation of Hemophilus. The exact nature of the virus-induced influences which enhance the pathogenicity of the bacteria and favor the establishment of the infectious process under these circumstances remains to be determined.
Resistance to streptomycin, of a degree exceeding 1000 microg. per ml., has been induced in sensitive strains of Hemophilus influenzae by exposure for 10 minutes to desoxyribonucleic acid-containing extracts isolated from a strain of type b Hemophilus influenzae which had emerged resistant to 1000 microg. of streptomycin per ml. DNA is essential for the process which brings out this change; the reaction can be prevented by destruction of the DNA with crystalline desoxyribonuclease.The resistant trait which is created in this way is heritable. The nature of the process which induces resistance is similar in all respects to the reaction which induces heritable changes in type specificity of H. influenzae. These results offer another example of the gene-like action of highly specific DNA's. The pattern of resistance brought out in a bacterial population exposed to the DNA-containing, resistance-inducing extract, is similar to that which occurs when emergence of resistance of H. influenzae to streptomycin follows the selection by streptomycin of spontaneously occurring resistant mutants. The change in a bacterial cell from average susceptibility to streptomycin to resistance to 1000 microg. of streptomycin per ml. can occur in a single step.
Hemophilus influenza is the causative organism in only 7%-11% of the cases of pyogenic pericarditis in children. A total of 36 cases have been reported in the literature since 1942. This report analyzes those cases, adds four more (ages 8 mo, 4 yr, 5 yr, and 7 yr), and recommends a plan of management. The diagnosis is suspected in a child with an acute febrile illness of less than seven days' duration who has an enlarged heart shadow on chest x-ray. Most patients have major associated conditions such as pneumonia or meningitis. The echocardiogram is the best modality for establishing the diagnosis. The characteristic feature of the disease is the thick fibropurulent pericardial fluid produced. This cannot be adequately managed with pericardiocentesis or tube peridcardiostomy. Complete anterior pericardiectomy is required to achieve adequate drainage. This must be combined with maximal doses of ampicillin and chloramphenicol. The overall mortality has been 20%, however, when aggressive surgical and medical therapy is used, the mortality rate is reduced to 7.4%. All of our patients treated in this manner survived.
Hemophilus influenzae infections are increasing in frequency in the general population. As a result this organism must be considered an etiologic agent of disease in the neonate. Proper culture technics must be routinely employed to isolate this fastidious organism, and appropriate antimicrobial therapy must be instituted in infants suspected of having sepsis or meningitis. Three cases of H influenzae infection occurring in neonates are presented.
Although Hemophilus influenzae infections have long been considered to be a disease of childhood, recent reports have demonstrated an increasing frequency of serious Hemophilus influenzae infections in adults. A case of purulent H. influenzae pericarditis in a previously healthy adult without evidence of concurrent H. influenzae infection is reported.
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Hemophilus influenzae isolates from sputum of 111 patients with chronic bronchitis were tested for susceptibility to 8 antimicrobial drugs. A new beta-lactam, LY-127935, was the most active agent tested. Ampicillin, cefamandole, tetracycline, and cefuroxime showed good activity against most isolates. Two strains, both nontypable, were resistant to ampicillin and produced beta-lactamase. Cefaclor was somewhat less effective, although most strains were susceptible. Erythromycin and cephalexin were of limited utility.
Ampicillin-resistant Hemophilus influenzae had not been identified in Fresno, California, before June 1976. In the 12 months that followed, eight resistant type B strains and three resistant nontypable isolates were cultured from patients treated at two hospitals that provide nearly all of the acute pediatric inpatient care for the area. Two of the resistant strains were obtained from patients with invasive infections and represented 4.2 percent of Hemophilus influenzae isolated from blood, cerebrospinal fluid or joint aspirates during the 12 months. The remaining six resistant type B strains were obtained from 117 patients, and were the predominant organism in cultures of other sites, primarily respiratory secretions. In two of three patients infected with nontypable organisms, resistance appeared to emerge during therapy with ampicillin. Measurement of beta lactamase was a practical and accurate method for differentiating between ampicillin-sensitive and resistant strains. All ten of the beta lactamase-positive isolates tested had minimal inhibitory concentrations (MIC) for ampicillin of 15 mug per ml, or less. In contrast 30 beta lactamase-negative strains had MIC's of 1.5 mug per ml, or less, of ampicillin. Our results indicate that ampicillin resistance has become a significant problem in the Central Valley of California and probably the entire state.
Hemophilus influenzae-transforming DNA, which has been inactivated by ultra-violet radiation, is reactivated by visible light in the presence of a cell-free extract of Escherichia coli B. The time rate of reactivation is increased by increasing the E. coli extract concentration, the temperature, and the intensity of illumination. Only DNA containing an ultraviolet-damaged genetic marker exhibits increased transforming activity after treatment with the photoreactivating system. The reactivating capacity of the extract remains in the top supernatant after centrifugation at 110,000 x g for 1 hour and is not present in the pellet. This capacity is destroyed by heating to 90 degrees C. for 1 minute. The active system of the E. coli extract is separable into dialyzable, heat-stable and non-dialyzable, heat-labile fractions. The dialyzable fraction contains at least one component which limits the maximum degree of recovery attained.
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Two new types of Hemophilus influenzae, Sab and Sad have been produced in vitro. Each exhibits the presence of the type specific polysaccharides of 2 types of E. influenzae within the same cell. In Sab the polysaccharides of types a and b have been demonstrated and in Sad those which characterize types a and d. The Sab and Sad traits are inherited. Sab was produced by the action of DNA-containing extract isolated from type a on either type b cells or Rb cells (non-encapsulated non-type-specific cells derived from type b). Sad cells were formed as a result of the action of the DNA-containing extract isolated from type d on cells intermediate between Rab and Sab cells. DNA-containing extracts isolated from Sab cells have induced the Sab trait in Rd cells with predictable regularity. Evidence has been presented that the hereditary determinant of Sab cells is a new genetic substance with new functions. Therefore, the interaction of the DNA-containing substance from cells of one genetic type with living cells of a genetically different type has produced what appears to be a new individual which differs from each of the cells contributing the differing genetic traits but has at least one trait in common with each. Sab cells derived presumably from a single cell show the appearance of type b cells sometime during the first 7 generations.
Hemophilus influenzae pneumonia was diagnosed in 41 adult patients based on cultures of blood, pleural fluid or transtracheal aspirate. Bacteremia occurred in all age groups, but was most frequent in patients over the age of 50 years with severe underlying pulmonary disease. Chest films usually demonstrated multisegmental or multilobar infiltrates without evidence of cavitation. Pleural involvement was evident in half of the patients, although empyema occurred infrequently. Mortality was almost always associated with serious underlying diseases and bacteremia. Encapsulated strains of H. influenzae (usually type B) were identified in 18 of 22 (82 per cent) patients. The use of transtracheal aspirations and the adoption of routine subculturing of blood cultures on chocolate agar appear to be important factors in our increased recognition of this disease.