Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a failure of pristinamycin treatment in a case of pneumonia caused by streptogramins B-type resistant pneumococcus. We suggest that (i) streptogramins therapy should be avoided, if a previous treatment failure has been observed with a macrolide and/or if the antibiogram shows the MLS(B) co-resistance phenotype, and (ii) beta-lactams should remain the first-line antibiotics used for treatment of pneumococcal respiratory infections.
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PMID:Failure of pristinamycin treatment in a case of pneumonia caused by a streptogramins B-type resistant pneumococcus. 981 26

Streptococcus pneumoniae is a significant human pathogen which is an important cause of pneumonia and bacteraemia. Over the past few years the incidence of antibiotic resistance among clinical isolates of S. pneumoniae has increased. Penicillin resistance is now widespread and the frequency of isolates that are resistant to erythromycin has risen. Erythromycin resistance in S. pneumoniae follows two basic patterns. The MLS erythromycin-resistant phenotype is due to the enzymatic methylation of ribosomal RNA that blocks erythromycin binding to the ribosome. Alternatively, in isolates of the M phenotype, a more recently documented mechanism, resistance is associated with an active efflux process that reduces intracellular levels of erythromycin. We used two-dimensional electrophoresis to examine the proteins synthesised by erythromycin-susceptible and -resistant S. pneumoniae. Erythromycin-resistant S. pneumoniae with the M phenotype showed a significantly increased synthesis of a 38,500 Dalton (pI 6.27) protein compared to susceptible isolates. Peptide mass mapping was used to identify the 38,500 Dalton protein as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). It was demonstrated that S. pneumoniae synthesised at least three forms of GAPDH that differed in their isoelectric points. The form of GAPDH possessing the most basic pI showed the increased synthesis in the erythromycin-resistant S. pneumoniae isolates. Alterations in the synthesis of GAPDH were only found for those erythromycin-resistant isolates possessing the M phenotype. S. pneumoniae isolates with the MLS phenotype were indistinguishable from the susceptible strains using the analytical conditions employed for the current study. The possible role of GAPDH in erythromycin resistance of S. pneumoniae is considered.
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PMID:A proteomic analysis of erythromycin resistance in Streptococcus pneumoniae. 1049 30

Telithromycin is the first member of a new family of the macrolide-lincosamide-streptogramin-B (MLS(B)) class of antimicrobials, the ketolides. It has a good spectrum of activity against respiratory pathogens, including penicillin- and erythromycin-resistant pneumococci, as well as intracellular and atypical bacteria. Furthermore, it has a low potential to select for resistance or induce cross-resistance among other MLS(B) antimicrobials. At the recommended dosage of 800 mg orally once daily, telithromycin reaches maximal plasma concentrations of about 2 mg/L. It penetrates rapidly into bronchopulmonary, tonsillar, sinus and middle ear tissues and/or fluids and achieves high concentrations at sites of infection. It also concentrates within polymorphonuclear neutrophils. In clinical trials in patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) or pharyngitis/tonsillitis caused by group A beta-haemolytic streptococci, telithromycin 800 mg once daily achieved clinical cure rates of 86 to 95%. In acute maxillary sinusitis (AMS), cure rates were 73 to 91%. A 7- to 10-day regimen of telithromycin was as effective as a 10-day course of amoxicillin 1000 mg 3 times daily, clarithromycin 500 mg twice daily or a 7- to 10-day course of trovafloxacin 200 mg once daily for treating CAP. A 5-day regimen of telithromycin was as effective as a 10-day regimen of cefuroxime axetil 500 mg twice daily or amoxicillin/clavulanic acid 500/125 mg 3 times daily in AECB. A 5-day regimen of telithromycin was as effective as a 10-day regimen of clarithromycin 250 mg twice daily or phenoxymethylpenicillin 500 mg 3 times daily in pharyngitis/tonsillitis, or a 10-day regimen of amoxicillin/clavulanic acid 500/125 mg 3 times daily in patients with AMS. Telithromycin was well tolerated across all patient populations. Adverse events associated with telithromycin were generally mild to moderate in intensity and seldom led to treatment discontinuation. The most frequent adverse events were diarrhoea (13.3%) and nausea (8.1%). Other adverse events included dizziness and vomiting.
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PMID:Telithromycin. 1139 13

Suppurative complications of Streptococcus pneumoniae infections have become uncommon in the antibiotic era. We report a case of pneumococcal bacteremia and pneumonia complicated with epidural abscess and endocarditis in which macrolide resistance (the MLS(B) phenotype) emerged during erythromycin therapy. Genetic determinants known to mediate the most common mechanisms of macrolide resistance (methylation of the 23S rRNA and antibiotic efflux) were not detected by polymerase chain reaction or DNA hybridization. Sequence analysis of the DNA encoding the 23S rRNA of the macrolide-resistant isolate from the patient demonstrated the replacement of adenine by thymine at position 2058 (A2058T) in 2 of 4 alleles. Clinicians should be alert to the possibility of the emergence of resistance during macrolide therapy for community-acquired pneumonia, particularly if suppurative complications of pneumococcal infection are suspected.
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PMID:Macrolide-resistant pneumococcal endocarditis and epidural abscess that develop during erythromycin therapy. 1252 63

A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.
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PMID:Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetylerythromycin A derivatives. 1280 Dec 34

For the time being telithromycin is the only representative of a new group of antibiotics - ketolides - available for clinical use. Its chemical structure is derived from erythromycin, but it is better resorbed from the digestive tract and is efficacious against most macrolide-resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes. Telithromycin is registered for the treatment of respiratory infections: sinusitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia and streptococcal tonsillopharyngitis. The drug is well tolerated. It is less likely to induce MLS(B) resistance than macrolides with a 14- or 15-member ring.
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PMID:[Telithromycin]. 1510 Sep 78

The emerging reports of clinical failures using macrolides and their associations with macrolide-resistant Streptococcus pneumoniae prompted us to review the literature describing these cases. Thirty-three cases reporting macrolide treatment failure during treatment of pneumococcal infections were available for review. The most prevalent diagnosis (24/27 or 88.8% of available diagnoses) was community-acquired pneumonia (CAP). Previous medical history included cardiopulmonary disease in eight (24.2%) and immunocompromised states in five (15.1%) patients. The majority, 31/33 (93.9%) of patients received oral macrolide treatment in an outpatient setting. S. pneumoniae was isolated from the blood in 26 (78.8%) of 33 patients, three (9.1%) patients had bacteria present in both blood and cerebrospinal fluid, two (6%) patients grew S. pneumoniae from blood and bronchial washings and two (6%) patients had positive sputum cultures. The MLS(B) phenotype was the most predominant phenotype present in 12 (63.2%) of 19 patients. After failing initial macrolide treatment, 26 (78.8%) of 33 patients received parenteral antibiotic treatment. Of 33 patients admitted to hospital, 29 (87.8%) had their outcome described as 'survived'.
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PMID:A review of clinical failures associated with macrolide-resistant Streptococcus pneumoniae. 1528 6

The efficacy and safety of azithromycin prophylaxis of community-acquired pneumonia (CAP) in young adults in a military training centre of the Ministry of Defence of the Russian Federation located in the Central European Region of Russia were studied. Two prophylactic regimens with azithromycin vs. the control were evaluated: azithromycin, 500 mg/w for 8 weeks (R1), azithromycin, 1500 mg once upon the enrolment (R2) and no drugs (R3). Nasopharyngeal carriage of Streptococcuspneumoniae and its susceptibility to antibacterials were estimated thrice: before the exposure, after the exposure within the 9th week and after the exposure within the 20th week. The MLS(B) phenotype was suspected when the isolates were resistant to erythromycin and clindamycin. During the observation period of 22 weeks CAP was diagnosed in 20.2% of 678 subjects in group R3, 8.6% of 508 subjects in group R1 (Risk Ratio =0.4, 95% Cl = 0.3-0.6) and 10.3% of 507 subjects in group R2 (Risk Ratio = 0.5, 95% Cl = 0.4-0.7). The S.pneumoniae carriage rate at visit 0 was 34-35%, within the 9th week it was 75, 66 and 50% (p<0.05) in groups R1, R2 and R3 respectively, and within the 20th week it was 69, 57 and 36% in the same groups (p<0.05). At visit 0 no macrolide resistance was detected in any of the 40 isolates tested. The background level of intermediate penicillin resistance was revealed in 0-14% of the isolates. Dramatic growth of macrolide resistance was observed within the 9th week in group R1 (95.7%, 44 resistant strains, Azithro+Clinda resistance in 37% of them) and in group R2 (89.5%, 34 resistant strains, Azithro+Clinda resistance in 11.9% of them). By the 20th week the resistance rate decreased up to 40 % (16 resistant strains, Azithro+Clinda resistance in 10% of them) in group R1 and up to 22.6% (7 resistant strains, Azithro+Clinda resistance in 5.4% of them) in group R2. As for penicillin resistance, no unfavourable shifts were detected. The study demonstrated the effectiveness of the azithromycin prophylaxis of CAP in healthy young men at high transient risk of the disease, as well as the possible risk for selection of resistant endemic pathogens.
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PMID:[Efficacy and safety of azithromycin prophylaxis of respiratory tract infections in military community]. 1572 44

Methicillin-resistant Staphylococcus aureus (MRSA) should no longer be regarded as a strictly nosocomial pathogen. During the past decade, community-acquired MRSA (CA-MRSA) infections among young persons without healthcare-associated (HCA) risk factors have emerged in several areas worldwide. These infections are caused by strains that almost exclusively carry the staphylococcal cassette chromosome mec type IV element and the Panton-Valentine leukocidin genes and, unlike HCA-MRSA strains, are not multiresistant. Although the majority of CA-MRSA infections are mild skin and soft tissue infections, severe life-threatening cases of necrotizing pneumonia, necrotizing fasciitis, myonecrosis and sepsis have been reported. Clindamycin is an effective agent for skin and soft tissue infections, however attention should be paid to the possibility of the emergence of resistance during treatment in strains with the macrolide, lincosamide and group B streptogramin (MLS(B))-inducible resistance phenotype. For patients with invasive infections that may be caused be CA-MRSA, vancomycin, teicoplanin and linezolid represent appropriate empirical therapeutic options.
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PMID:Community-acquired methicillin-resistant Staphylococcus aureus infections. 1642 9