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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

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

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

[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

Minocycline treatment failure in pneumonia caused by minocycline-sensitive Streptococcus pneumoniae.

A previously healthy 23-year-old white woman had fulminant pneumococcal pneumonia complicated by empyema and bilateral pneumothoraces. Despite early treatment with the recommended doses of minocycline, the disease progressed. The S pneumoniae isolate was resistant to a 30microgram tetracycline disk and showed an MIC of 3.13microgram/ml for minocycline and 12.5 microgram/ml for tetracycline; these levels are considered by the manufacturer to indicate sensitivity to minocycline and intermediate sensitivity to tetracycline. The tetracyclines, including minocycline, should not be used to treat bacterial pneumonia since resistant strains of pneumococci are not uncommon and inffective treatment can lead to rapid progression of the infection. This case suggests that the levels of minocycline considered to indicate sensitivity in vitro be reassessed.

Adult

Legionnaires' disease pneumonia: histopathologic features and comparison with microbial and chemical pneumonias.

The histopathologic findings in lung tissue are reported from five cases of Philadelphia Legionnaire's Disease and the results are compared to pneumonias caused by other microbial and chemical agents. Histopathology of lung tissue was similar in all cases, despite the fact that death occurred between the fourth and 14th day of clinical illness. The inflammatory response was almost totally limited to the lower respiratory tract and primarily involved respiratory bronchioles, alveolar ducts and alveoli. Major bronchial branches and pulmonary interstices showed little or no involvement. There was considerable variation in the extent and nature of the consolidation, but the overall reaction pattern was highly characteristic of diffuse alveolar damage. Most involved areas showed intra-alveolar, fibrinocellular mononuclear cell predominant exudates, associated with pneumonocytic hyperplasia and slough. These findings plus the presence of erythroleucophagocytosis by macrophages and paucity of polymorphonuclear leucocytes are commonly associated with psittacine pneumonia, and much less so with classic patterns of bacterial, viral, fungal or rickettsial pneumonias. Of the toxic inhalants, nickel carbonyl, phosgene, nitrous oxide, cadmium oxide and some halogenated hydrocarbons have been associated with this tissue reaction pattern. Bacteria were notably absent in lung tissue stained by methods used to demonstrate the Legionnaires' Disease agent.

Adult

Pneumonia and pneumococcal infections, with special reference to pneumococcal pneumonia. The 1979 J. Burns Amberson lecture.

An etiologic classification of acute pneumonia was presented and the relative importance of some of the causative agents was briefly reviewed. The early developments of the therapy of pneumococcal pneumonia with type-specific antisera, sulfonamide drugs, and antimicrobial drugs were reviewed, mostly from the experiences of the author at Boston City Hospital. Changes in the occurrence and relative importance of the pneumococcus as a cause of infections associated with bacteremia, empyema, and meningitis were demonstrated, based on cases observed at Boston City Hospital during 12 selected years between 1935 and 1972. These findings, among others, indicate that the pneumococcus is still one of the most important causes of serious bacterial infections and of mortality from such infections, particularly in the elderly. Some possible indications for polyvalent pneumococcal capsular polysaccharide vaccine were discussed, and the need for further extensive clinical and field trials to demonstrate its range of effectiveness was stressed.

Age Factors

[Liebow's desquamative pneumonia--a separate disease entity or a form of chronic interstitial pneumonia? (author's transl)].

When in 1965 Liebow first described desquamative interstitial pneumonia (DIP) and differentiated it from other types of interstitial pneumonia he believed it to be a separate disease entity. The fact that the observed cases were of a relatively benign nature seemed to confirm this view. However, during the past years there have been reports of cases which took a less benign course; it was also observed that disorders with features similar to DIP could be produced by various exogenous noxae. The question, therefore, arises, whether DIP is, in fact, a separate disease entity or a specific pulmonary reaction to a variety of similarly acting noxae.

Humans

[Cyclodextrin glucanotransferase from Klebsiella pneumoniae. 1. Formation, purification and properties of the enzyme from Klebsiella pneumoniae M 5 al (author's transl)].

1. The strain M 5 al of Klebsiella pneumoniae grows excellently with starches. We were able to show that besides the pullulanase associated with the external membrane of the cells the bacterium produces an inducible, extracellular cyclodextrin glucanotransferase [1,4-alpha-D-glucan-4-alpha-(1,4-alpha-glucano)-transferase (cyclising) (EC 2.4.1.19)]. Potato starch and cyclohexaamylose or cycloheptaamylose were found to be the best "inducing" carbon sources for the synthesis of the enzyme. When the bacteria are grown batchwise, maltose is a poorly "inducing" carbon source; larger quantities of the enzyme are synthesized by continuous cultivation with maltose as growth limiting factor. 2. For the determination of the cyclodextrin glucanotransferase-activity an assay method wsa worked out. 3. The enzyme could be separated from the culture filtrate and purified to more than 90% in few steps. At a total yield of 61.2% related to the activity of the culture filtrate employed we received an enzyme solution with the specific activity of 26.6 units/mg protein. Some properties of the enzyme are described. 4. The products formed from amylopectin by the enzyme were analyzed. Somewhat more than half the amylopectin was found as cyclodextrins. 29.3% of the cyclodextrin fraction were cycloheptaamylose, 47.2% cyclohexaamylose and 10.7% exo-branched cyclohexaamylose. 12.8% of cyclohexaamylose were obtained from a cyclodextrin glucanotransferase-limit dextrin after debranching by pullulanase and exposing the product to the action of the glucanotransferase again. 5. The importance of the cyclodextrin glucanotransferase for the utilization of starches by this strain of Klebsiella pneumoniae is discussed. After a first characterization the enzyme is compared to the amylase of Bacillus macerans.

Amylopectin

Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients.

All 744 patients admitted to a Respiratory-Surgical Intensive Care Unit (RSICU) were included in a prospective study of the effects of a polymyxin (2.5 mg/kg body wt/day in six divided doses) or a placebo aerosol sprayed into the posterior pharynx and tracheal tube (if present), during 11 alternating 2-mo treatment cycles. The incidence of upper airway colonization in the RSICU with Pseudomonas aeruginosa was 1.6% during the polymyxin treatment cycles (total 374 patients) and 9.7% during the placebo cycles (370 patients) (X2 equals 23.2, P less than 0.01). 3 patients in the RSICU acquired Pseudomonas pneumonia, as defined by independent "blinded" assessors, during the polymyxin cycles while 17 acquired a Pseudomonas pneumonia during the placebo cycles (X2 equals 10.2, P less than 0.01). The overall mortality was similar in both placebo and polymyxin-treated groups (12.2 vs. 12.0%). Systemic antibiotic usage was similar in the different cycles; 49% of patients in the placebo and 53% in the polymyxin-treated groups received systemic antibiotics while in the RSICU.

Aerosols

Recurrent pneumonia and encephalitis due to Mycoplasma pneumoniae.

Recurrent Mycoplasma pneumoniae encephalitis in a young man is reported. The patient appeared not to be immunodeficient and despite the presence of a focal inflammatory brain lesion with a predominance of polymorphonuclear cells no direct evidence of inent in M. pneumoniae respiratory tract infection still is unknown the case strongly indicates that certain individuals are somehow predisposed to such complications. The case also illustrates that CNS complications may occur even during a mild mycoplasma respiratory tract infection and that the radiological findings can mimic cerebral haemorrhage or abscess necessitating neurosurgical exploration.

Adult

[Chronic progressive interstitial pneumonia in sheep (adenovirus pneumonia)].

Adenoviral infection was established in imported specialized meat strains of sheep Ile de France and Romni marsh. The disease followed a course typical of chronic interstitial progressive pneumonia with reduced tonus, loss of body weight, and high lethality. The disease was serologically proven by the discovery of specific complement binding antibodies in dynamics against the adenovirus. Titers varied from 1 : 2 to 1 : 32. The infestation was reproduced on sheep and lambs by tracheal infection with ultrafiltrate of changed lung tissue and bronchial lymph nodes. Morphologically the infection manifests itself by considerable hypeplastic processes in the lungs and less pronounced ones in the liver and kidneys. The typical changes indicated are accumulation of lymphoid cells and histocytes in the interstitial tissue, as well as adenomatous expansion of alveolar and bronchial epithelium. Considerable cell polymorphism is observed in the alveoles along with presence of gigantic cells and cell syncytia of desquamous epithelial cells, alveolar macrophages and intranuclear inclusions in some of these cells. Complications of Past. Haemolytica with developing catharalsuppurative pneumonia were observed in some cases.

Adenoviridae Infections

Temperature-sensitive mutants of Streptococcus pneumoniae. I. Preparation and characterization in vitro of temperature-sensitive mutants of type I S. pneumoniae.

After exposure of type I Streptococcus pneumoniae to nitrosoguanidine, 13 temperature-sensitive (ts) mutants were selected that were restricted in capacity to form colonies on blood agar at 38 C. Whereas colony formation by the type I parent (ts+) was unaffected by a temperature of as high as 39 C, the ts mutants exhibited a spectrum of temperature sensitivity in which colony formation was inhibited significantly at 36 C, 37 C, 38 C, or 39 C. Growth of ts mutants at 38 C in broth was reduced or delayed relative to that of ts organisms under identical conditions. In general, there was a direct correlation between degree of temperature sensitivity and genetic stability. Mutants grown at a permissive temperature resembled the ts+ type I parent in colonial morphology and properties of alpha-hemolysis, bile solubility, optochin sensitivity, and antibiotic sensitivity. Moreover, in vitro studies indicated that the mutants retained capsules of immunochemically reactive type I capsular polysaccharide.

Bile