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Mycoplasma pneumoniae and the aetiology of lobar pneumonia in northern Nigeria.

Over a six-month period we studied 74 adult Nigerians who presented consecutively to Ahmadu Bello University Teaching Hospital, Zaria, with lobar or segmental pneumonia. Pneumococcal infection was diagnosed in 50% by the detection of pneumococcal polysaccharide antigen in serum or purulent sputum: 24% had pneumococcal antigenaemia. Twelve patients had evidence of Mycoplasma pneumoniae infection and half of these also had pneumococcal infection. The suggestion that M pneumoniae respiratory infection may predispose to serious bacterial pneumonia is discussed. The initial clinical and radiological features were similar in the pneumococcal and M pneumoniae groups. Raised cold agglutinin titres were not a reliable indication of M pneumoniae infection, perhaps due to altered autoantibody production in Nigerians. Pneumonia was commoner in the dry season, probably related to depressed nasopharyngeal defences caused by drying. Less common causes of lobar pneumonia that were found are also discussed and no cases of legionnaires' disease were identified.

Adult

KpSC-ID: a multiplex real-time PCR assay for the simultaneous detection of the Klebsiella pneumoniae species complex and specific identification of Klebsiella pneumoniae, Klebsiella quasipneumoniae and Klebsiella variicola.

The Klebsiella pneumoniae species complex (KpSC) comprises five closely related bacterial species, namely Klebsiella pneumoniae, Klebsiella quasipneumoniae, Klebsiella variicola, Klebsiella quasivariicola and Klebsiella africana. The KpSC is ubiquitous in the environment and is also an important human pathogen, particularly associated with healthcare-associated infections. The accurate detection and differentiation of the KpSC is challenging owing to the close phenotypic and genotypic identity (93-95% average nucleotide identity) shared between these members. Current diagnostic assays either fail to detect and identify all KpSC members or misidentify some KpSC members as K. pneumoniae sensu stricto. It is currently estimated that ~20% of human infections are caused by members of the KpSC other than K. pneumoniae. This leads to underreporting of some KpSC members in both clinical and environmental settings, which impacts our understanding of the importance of each species. Furthermore, it limits our understanding of the global and local epidemiological impact of some members of the KpSC. In this study, a rapid multiplex real-time PCR assay (KpSC-ID) was designed and developed to detect all KpSC members while simultaneously identifying the predominant human pathogens K. pneumoniae, K. quasipneumoniae and K. variicola. Assay performance was verified in silico using a panel of over 1,000 publicly available genome sequences and experimentally validated using a panel of genomic DNA extracted from 54 Enterobacteriaceae. The assay displayed excellent specificity against over 1,000 genome sequences tested in silico. During in vitro validation, the pan-KpSC assay detected each (29/29) KpSC species and strains tested. For the species-specific assays, 100% specificity was demonstrated in the K. pneumoniae, K. quasipneumoniae and K. variicola assays, respectively. Sensitivity of 10 genomic equivalents was demonstrated for each assay. Ultimately, the diagnostic assay developed in this study can improve our understanding of the significance of KpSC members, which is important when investigating their routes of transmission and epidemiology.

Klebsiella

Genomic and phenotypic characterization of Klebsiella pneumoniae phage KP Ø1: a novel lytic Slopekvirus targeting uropathogenic multidrug-resistant Klebsiella pneumoniae.

The rise of multidrug-resistant (MDR) uropathogenic gram-negative bacteria (GNB) necessitates the development of alternative therapeutic strategies. This study aimed to isolate, phenotypically characterize, and perform whole-genome sequencing of the bacteriophage demonstrating the broadest host range against MDR uropathogens. Fifty MDR GNB isolates were screened for lytic phages. The most promising candidate, Klebsiella pneumoniae phage KP Ø1, was characterized using plaque assay, Transmission Electron Microscopy (TEM), and pH/thermal stability testing. Genomic characterization was performed via whole-genome sequencing (WGS), with functional annotation and lifestyle prediction using PhaBOX and PhageScope software. Klebsiella pneumoniae was the most prevalent MDR uropathogen. Klebsiella pneumoniae phage KP Ø1 exhibited a 50% host range and high lytic titer (10⁸ PFU/mL). TEM revealed an icosahedral head and short contractile tail. Genomic characterization by WGS revealed that Klebsiella pneumoniae phage KP Ø1 possesses a 174,591 bp double-stranded deoxyribonucleic acid (dsDNA) genome containing 274 predicted open reading frames (ORFs). No lysogeny-related genes, toxins, or antibiotic resistance markers were detected, confirming its strictly lytic nature and supporting its potential as a candidate for phage therapy applications. The phage remained stable (10⁸ PFU/mL) across temperatures of - 20 °C to 50 °C; supporting its suitability for long-term biobanking and suggesting potential activity at physiological temperature, and across a pH range of 7-9. Klebsiella pneumoniae phage KP Ø1 is a novel, obligately lytic Slopekvirus whose genomic architecture, stability profile, and absence of lysogeny-associated, virulence, and antimicrobial resistance genes ( AMR) collectively support its candidacy for further preclinical evaluation as a phage therapy agent against uropathogenic MDR Klebsiella pneumoniae.

Klebsiella pneumoniae

Second attacks of pneumonia due to Mycoplasma pneumoniae.

Long-term surveillance of pneumonia in a group that received prepaid medical care disclosed five cases of pneumonia due to Mycoplasma pneumoniae that recurred in immunocompetent persons after a lapse of two and one-half to 10 years. Diagnosis was confirmed by isolation of M. pneumoniae, by observation of changes in titer of antibody, and by chest films. In addition, a patient with a variable immunodeficiency syndrome that affected the bone marrow-derived (B-) cell system had recurrent infection with M. pneumoniae within a one-year interval. Naturally acquired immunity to infection with M. pneumoniae appears to be of limited duration.

Humans

Comparison of josamycin and erythromycin in the therapy of Mycoplasma pneumoniae pneumonia.

A controlled, double-blind study was performed to compare the efficacy of two macrolide antibiotics, erythromycin and josamycin, in the therapy of Mycoplasma pneumoniae pneumonia. Marine Corps recruit volunteers received one of the two antibiotics in a dosage of 2 g daily for 7 days. Twelve of 21 men treated with josamycin and 9 of 25 men treated with erythromycin had confirmed M. pneumoniae pneumonia. The josamycin-treated group remained hospitalized for 5.4 +/- 1.2 days compared to 5.1 +/- 2.0 days for the erythromycin-treated group (0.60 > P > 0.50). Fever days were similar for the josamycin-treated (1.4 +/- 0.4) and erythromycin-treated (1.2 +/- 0.3) groups (P = 0.95). There was no difference in resolution of signs and symptoms of illness in the two study populations. Thus, josamycin is as efficacious as erythromycin in the therapy of M. pneumoniae pneumonia.

Anti-Bacterial Agents

Spread of Streptococcus pneumoniae in families. II. Relation of transfer of S. pneumoniae to incidence of colds and serum antibody.

Factors that affect the spread of Streptococcus pneumoniae and the antibody responses associated with colonization were studied in 64 families for periods of eight to 52 weeks. Surveillance included daily recording of respiratory symptoms and bimonthly pharyngeal cultures for identification of the pneumococcal carrier state. Rhinovirus cultures were included for a portion of the study period. Intrafamilial carriage of a single type of S. pneumoniae and simultaneous spread to more than one family member were commonmspread often occurred in association with an upper respiratory tract infection; simultaneous transmission of S. pneumoniae and a rhinovirus was documented. Preexisting, type-specific serum antibody did not prevent acquisition of homotypic S. pneumoniae but did appear to shorten the duration of pharyngeal carriage. Sera of all 11 adults had greater than 150 ng of antibody nitrogen/ml of homotypic serum antibody (measured by a radioimmunoassay) before colonization. In contrast, only one of 13 preschool children had homotypic antibody concentrations of this magnitude before colonization. A threefold or greater rise in the concentration of homotypic antibody occurred in 13 of 24 children (54%) after acquisition of S. pneumoniae; the increase in antibody concentration was associated with illness in six of the children. On the other hand, acquisition of S. pneumoniae in adults was not associated with an increase in concentration of homotypic serum antibody.

Adult

Immunoprophylaxis of experimental Mycoplasma pneumoniae disease: effect of route of administration on the immunogenicity and protective effect of inactivated M. pneumoniae vaccine.

Formalin-inactivated Mycoplasma pneumoniae vaccine was administered subcutaneously or intranasally to hamsters to examine the effect of route of administration on immunogenicity and protective effect. Parenterally administered vaccine in the doses employed induced serum complement-fixing antibody formation, but did not significantly decrease the frequency of pneumonia following challenge with virulent M. pneumoniae. Intranasally instilled vaccine was ineffective in stimulating serum antibody, but did diminish the frequency of experimentally induced pneumonia due to M. pneumoniae. However, a greater degree of resistance was induced by intranasal infection with either wild-type organisms or the ts 640 attenuated mutant of M. pneumoniae.

Administration, Intranasal

[Pathological anatomy of pneumonia in Mycoplasma pneumoniae infection in children].

A total of 43 section observations on acute respiratory viral diseases in children aged between 13 days to 13 years are described. Using the direct and indirect fluorescent antibody test in 11 observations M. pneumoniae antigen was detected; in 4 observations this antigen was represented as monoantigen, and in 7 observations--in association with viruses of influenza, parainfluenza and adenovirus. The characteristic features of mycoplasma pneumoniae were noted; very high blood filling of vessels of all calibres with the involvement of the system of microcirculation of the lungs, with phenomana of pronounced dilatation of the capillary net and with a tendency to thrombo-formation; diffuse lesions (dystrophic and inflammatory changes) of large and small bronchi and bronchioles; plasmocellular reaction in interstitia of the lungs, perbronchial follicles and bifurcated lymphatic nodes; the presence of M. pneumoniae antigen in histological sections of the lungs. The author thinks it advisable to discard the term "M. pneumoniae-pneumonia" and replace it by "M. pneumoniae-infection" with predominent localization of the process in the lungs.

Animals

Survival of Streptococcus pneumoniae in sputum from patients with pneumonia.

The isolation rate of Streptococcus pneumoniae in sputum cultures from patients with pneumococcal pneumonia is low. An investigation was made to determine whether this low yield might be due to loss of pneumocci and/or overgrowth by pharyngeal flora before the specimen is plated. Pneumococcal survival times and pharyngeal overgrowth at 4 degrees C and at room temperature were determined in sputum obtained from 42 patients with pneumococcal pneumonia. It was found that pneumococci survived for long periods in sputum--2.2 +/- 1.4 days at room temperature and 9.5 +/- 3.6 days at 4 degrees C. Overgrowth by pharyngeal flora occurred in only 6 of 42 specimens kept at 4 degrees C and 31 of 42 specimens kept at room temperature. The low yield of S. pneumoniae in sputum from patients with pneumococcal pneumonia is not explained by decreased viability of the organism.

Adult

Cefamandole vs. procaine penicillin for treatment of pneumonia due to Streptococcus pneumoniae: a random trial.

The efficacy and safety of cefamandole nafate and penicillin G procaine suspension were compared in the treatment of pneumococcal pneumonia in hospitalized adults. One hundred thirteen patients with clinical and radiographic evidence of pneumococcal pneumonia were randomly assigned to receive 600,000 units of procaine penicillin intramuscularly every 12 hr or 500 mg of cefamandole intramuscularly every 6 hr. The two groups were comparable with regard to patient type and extent and severity of pneumonia. Alcohol abuse was a host factor in 31% of all patients in the trial. All strains of Streptococcus pneumoniae isolated were inhibited by less than or equal to 1.6 microgram of cefamandole/ml. Of 58 patients treated with cefamandole, 50 had a satisfactory response, as did 46 of the 55 patients treated with penicillin. Results of tests of liver function were abnormal (primarily, elevated levels of transaminase or alkaline phosphatase) in 38% of the entire group of patients and occurred with equal frequency in patients receiving cefamandole or penicillin. Side effects during therapy, including superinfection, occurred equally with either drug. In a random trial, cefamandole was as effective and safe as penicillin in the treatment of pneumococcal pneumonia in adults.

Adult

Mycoplasma pneumonia: a study on hospitalized American patients with pneumonia in Vietnam.

A prospective study on consecutively hospitalized pneumonia patients showed that 41.5% of 58 patients had a fourfold rise in the complement-fixation titer for Mycoplasma pneumoniae. Viral isolation techniques and serologic tests for influenza A1, A2 and B, parainfluenza 1 and 3, respiratory syncytial virus and the adeno virus group yielded only a single positive isolate for influenza A2. Serologic tests for melioidosis, leptospirosis, scrub, murine and epidemic typhus and psittacosis were all negative. The clinical manifestations were not distinctive for the positive M. pneumoniae patients when compared with the patients having a negative M. pneumoniae complement-fixation test. The symptoms and signs and laboratory and radiologic findings were similar to those described in other reports on primary atypical pneumonia.

Adult

[Therapeutic effect of midecamycin on Mycoplasma pneumoniae pneumonia in adults (author's transl)].

The clinical efficacy of a macrolide antibiotic, midecamycin, was studied in 12 adult cases with Mycoplasma pneumoniae pneumonia. The therapeutic effects were excellent or good in 9 cases and fair in 2 cases. On defervescence and disappearance of shadows on chest X-ray the therapeutic effect was satisfactory, but on disappearance of cough therapeutic effect was not clear in some cases. Taking into consideration the antimicrobial activity of midecamycin against Mycoplasma pneumoniae, serum concentration and side effects of midecamycin, this antibiotic is expected to be effective in the treatment of Mycoplasma pneumoniae pneumonia.

Adolescent

Acquired immunity to Mycoplasma pneumoniae. Pneumonia in hamsters.

An inactivated Mycoplasma pneumoniae vaccine was prepared from a culture in a liquid medium supplemented with water extract of egg yolk. Vaccinated Syrian hamsters were exposed to virulent M. pneumoniae aerosol and were examined for the retention of mycoplasmas and for histopathological changes in the respiratory tracts. When a vaccine prepared with strain FH was administered intramuscularly or by inhalation in aerosol, no significant resistance was shown with respect to mycoplasma proliferation. An increased resistance, however, was observed when an aluminium phosphate-adsorbed vaccine, and when a plain vaccine (although to a lesser degree) prepared with hamster 24-passaged strain FH, was administered intramuscularly. Histopathologically, lung lesions were markedly suppressed in groups showing high resistance. A correlation between the serum antibody titer and the resistance to infection was observed. Hamsters which received a hyperimmune rabbit antiserum intracordally showed a high resistance to M. pneumoniae infection. The suppression of histopathological changes also coincided with high complement-fixing antibody titers of either actively or passively immunized hamster serum. The results suggest that humoral immunity plays an important role in resistance to M. pneumoniae pneumonia in hamsters.

Adjuvants, Immunologic

The radiographic resolution of Streptococcus pneumoniae pneumonia.

To determine the characteristics of the radiographic resolution of bacteremic Streptococcus pneumoniae pneumonia we examined serial chest roentgenograms in 72 patients. Consolidation disappeared in all patients by eight to 10 weeks; volume loss (9 per cent), plural disease (9 per cent), and stranding (19 per cent) often persisted beyond eight weeks. Resolution occurred earlier in patients less than 50 years old (P less than 0.05) and in the absence of alcoholism and underlying airways disease regardless of age (P less than 0.05). Delayed clearing occurred when these complicating factors were present in patients over 50. Lung cancer was not responsible for delayed resolution of pneumonia. We conclude that an appropriate interval for serial radiographic examinations after therapy for pneumococcal pneumonia is six weeks.

Aging

[The therapeutic effect of doxycycline (Vibramycin) on pneumonia due to mycoplasma pneumoniae (author's transl)].

Tetracycline is expected to be as effective as erythromycin in the treatment of pneumonia due to Mycoplasma pneumoniae. In this clinical trial 12 cases with pneumonia due to Mycoplasma pneumoniae were given doxycycline (Vibramycin "Pfizer'), a long-acting derivative of tetracycline. Judging from time periods required for defervescence, improvement in symptoms such as cough and disappearance of shadows on chest X-ray, the therapeutic effect of doxycycline was excellent in 8 cases and good in 4 cases.

Adolescent