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)

During the last few years, acquired resistance of pneumococci to the main families of normally active antibiotics has appeared. This resistance is now worldwide but unevenly distributed: in Europe, for instance, it predominates in Spain and Hungary. In France, according to the national Registry, resistance to penicillins, which was less than 5 percent in 1988, rose to 16.9 percent in 1991. More than 80 percent of resistant strains are found among 4 stereotypes (6, 9, 19, 23) and more than 50 percent belong to stereotype 23F exclusively. The incidence of penicillin-resistant has been evaluated at 8.5 percent in the year 1991-92. The most significant risk factor is a previous treatment with beta-lactam antibiotics, but some authors also blame frequent pneumonias in the previous year, nosocomial pneumonia, or hospitalization during the previous 3 months. There are no specific clinico-radiological features. The incidence of resistant strains is said to be higher in HIV seropositive subjects. Amoxicillin administered in high doses remains the reference treatment for strains with intermediate susceptibility (minimal inhibitory concentration [MIC] between 0.1 and 1.0 microgram/ml). Strains with a more than 1 microgram/ml MIC require beta-lactam antibiotics such as ceftriaxone, cefotaxime of imipenem in high doses. Pristinamycin still has good in vitro activity on resistant strains. Prevention rests on isolation of infected patients, treatment of healthy carriers and wide prescription of anti-pneumococcus vaccine.
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PMID:[Pneumonia caused by resistant pneumococci]. 837 82

The efficacy and safety of a three-day regimen of azithromycin (500 mg od) and a ten-day regimen of co-amoxiclav (625 mg tid) were compared in a single-blind study in 99 patients with acute lower respiratory tract infections. Of these, 70 (71%) suffered an infective exacerbation of their chronic obstructive pulmonary disease. Nine patients had pneumonia and 19 purulent bronchitis. Treatment success, defined as cure or improvement, occurred in 43 of 48 (90%) patients in the azithromycin group, compared with 45 of 51 (88%) patients in the co-amoxiclav group. The most common isolated pathogens were Haemophilus influenzae (25 cases; MIC range of azithromycin (A) < or = 0.06-4 mg/L; for co-amoxiclav (CA) 0.25-4 mg/L; Streptococcus pneumoniae (10 cases; A: < or = 0.06- > 128; CA: < or = 0.06); and Moraxella catarrhalis (four cases; A: < or = 0.06; CA: < or = 0.06-0.25). Microbiological response rates were comparable in the two groups. In 5% of patients, serological evidence for virus or atypical pathogens was found. Thirteen (26%) patients treated with co-amoxiclav had gastrointestinal complaints (seven with diarrhoea), compared with five (10%) treated with azithromycin (P = 0.09). Additional complaints occurred in three patients treated with co-amoxiclav and in one patient treated with azithromycin. It was concluded that a three-day regimen of azithromycin was as effective, clinically and microbiologically, as a ten-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections.
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PMID:A single-blind comparison of three-day azithromycin and ten-day co-amoxiclav treatment of acute lower respiratory tract infections. 839 86

FK037 exhibits potent in vitro and in vivo antibacterial activity against methicillin-resistant staphylococci. In in vitro studies, FK037 was the most active of the cephalosporins and imipenem tested against the highly methicillin-resistant staphylococci (MIC > 100 micrograms/ml). Only 2 of 57 strains of highly methicillin-resistant Staphylococcus aureus (H-MRSA) had a FK037 MIC value of 50 micrograms/ml. On the other hand, 55, 40 and 19 strains had MICs of 50 or > or = 100 micrograms/ml to cefpirome, flomoxef and imipenem, respectively. Against 13 strains of highly methicillin-resistant coagulase-negative staphylococci (H-MRCNS), FK037 inhibited all the strains at < or = 50 micrograms/ml, but there were many strains highly resistant to the reference drugs with MICs of > or = 100 micrograms/ml. The influence of culture conditions such as low temperature, high inoculum and supplementation with 4% NaCl on the anti-MRSA activity of FK037 was less than those with cefpirome, flomoxef and imipenem. The in vitro frequency of spontaneous mutant cells highly resistant to FK037 in MRSA was lower than that to cefpirome and flomoxef. These findings were supported by lack of colonies inside the inhibition zone demarcated by FK037 in a disk sensitivity test, although many colonies proliferated inside the inhibition zone demarcated by flomoxef and imipenem. The increase in MIC of FK037 against a MRSA strain during subculture in the presence of the drug was smaller than that noted with the reference drugs. FK037 had higher affinity and faster binding for the PBP 2a of MRSA than that of the reference drugs. Moreover, the capacity to induce PBP 2a was lower for FK037 than that of cefpirome but higher than that of flomoxef. In an in vitro pharmacokinetic model simulating human plasma concentrations, FK037 showed potent bactericidal activity against H-MRSA in the plasma concentrations after intravenous infusion dosing with 1.0 g. FK037 was synergistically active against H-MRSA in combination with either imipenem of fosfomycin. The in vitro post-antibiotic effect (PAE) of FK037 against H-MRSA ranged from 1.2 to 1.7 hours at one to four times the MIC. FK037 had potent therapeutic effects against lethal systemic infections and experimental local infections in mice such as pneumonia, endocarditis, subcutaneous abscess, intrauterine infection and granuloma pouch infection due to MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE). FK037 was about 4, 8 and 1.5 times more effective than cefpirome, flomoxef and imipenem, respectively, against lethal systemic infections with H-MRSA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Excellent activity of FK037, a novel parenteral broad-spectrum cephalosporin, against methicillin-resistant staphylococci. 843 64

FK037, a new parenteral cephalosporin, is an oxime-type cephem antibiotic with a 1-hydroxyethyl-5-amino-pyrazole moiety at the 3 position. FK037 was evaluated for antimicrobial activity in vitro and in vivo. In vitro, FK037 was twofold or more active than ceftazidime, cefoperazone, cefotaxime, and ceftriaxone against Pseudomonas aeruginosa (MIC for 90% of the strains [MIC90] = 32 micrograms/ml), members of the family Enterobacteriaceae (MIC90 < or = 2 micrograms/ml), group A streptococci (MIC90 = 0.015 microgram/ml), and methicillin-sensitive or -resistant coagulase-negative staphylococci (MIC90 = 2 and 16 micrograms/ml, respectively). In addition, the activity of FK037 was equal to or greater than that of ceftazidime, cefotaxime, or ceftriaxone against Streptococcus pneumoniae (MIC90 = 0.12 microgram/ml) and methicillin-sensitive or -resistant Staphylococcus aureus (MIC90 = 2 and 16 micrograms/ml, respectively). FK037 was more active in vitro than cefepime (two- to fourfold) and cefpirome (twofold) against S. aureus. In murine systemic infection models, FK037 showed potent activity against P. aeruginosa, Escherichia coli, and methicillin-sensitive and methicillin-resistant S. aureus. FK037 was also efficacious in a mouse model of pyelonephritis caused by S. aureus or Klebsiella pneumoniae and in a mouse model of pneumococcal pneumonia caused by S. pneumoniae. Additional studies on this compound to assess its potential clinical utility are warranted.
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PMID:In vitro and in vivo antibacterial activities of FK037, a novel parenteral broad-spectrum cephalosporin. 845 61

The effect of selective decontamination of the digestive tract on the nature and incidence of microbial biofilm formation on endotracheal tubes was assessed. Thirty endotracheal tubes were obtained post-extubation from patients in the intensive care unit who had been ventilated for a 1 to 15 day period and who did or did not receive the antibiotic regimen. Extensive biofilm formation was identified by scanning electron microscopy on 97% of tubes examined. Endotracheal tube biofilm in tubes obtained from patients who received selective decontamination of the digestive tract showed a high prevalence of colonization with yeast (4 of 15 tubes) and gram-positive bacteria (streptococci, staphylococci and diphtheroids) (14 of 15 tubes). Staphylococcus aureus was isolated only from this group. Pseudomonas spp. were isolated from 2 of 15 tubes in both patient groups. Enteric gram-negative organisms (coliforms, Klebsiella and Proteus spp.) were isolated only from tubes of patients who did not receive the antibiotic regimen (4 of 15 tubes). Yeasts, however, were not isolated from these tubes. Group D streptococcal isolates were resistant to tobramycin as were half of the Staphylococcus aureus isolates. For gram-negative bacteria, the MIC of tobramycin was in the range 1-64 micrograms/ml and the MIC of polymyxin in the range 0.5-16 micrograms/ml. Although a reduction was observed in the incidence of gram-negative microorganisms, this antibiotic regimen does not inhibit biofilm formation on the endotracheal tube by other pathogens associated with pneumonia in ventilated patients. This persistent nidus may be a factor in the pathogenesis of nosocomial pneumonia.
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PMID:Influence of selective decontamination of the digestive tract on microbial biofilm formation on endotracheal tubes from artificially ventilated patients. 846 71

The relations between the clinical efficacy, phagocytic transport phenomena, tissular and sera kinetics have been assessed in a pneumonia murine model. At first, the correlation between the clinical efficacy and pharmacokinetics characteristics has been studied for the erythromycin, spiramycin, roxithromycin, clarithromycin and azithromycin. An in vivo clinical efficacy hierarchy has been established (azi > ery > roxi = azi > spira). A hierarchy identical to the clinical efficacy, has been recognised for the pulmonary elimination half lives and the pulmonar AUC. These could be considered as predictive of these antibiotics activity in the respiratory infections. In a second time, the tissular pharmacokinetics of the azithromycin in leukopenic mice allowed to confirm the leukocytes role in the transport and release of this antibiotic in the midst of the infections site. Finally, this antibiotic demonstrated its efficacy in a bacterienic infection even when administered at a low dosage thus allowing to have sera concentrations identical to those obtained in human clinical case and close to MIC's for S. pneumoniae. The pharmacokinetic novelty displayed by its strong tissular penetration can explain its remarkable efficacy.
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PMID:[The particular case of azalides: antibiotic diapedesis. Experimental data from a murine model of pneumococcal pneumonia]. 853 75

In 1875, 7 years prior to the description of the Koch bacillus, Klebs visualized the first Streptococcus pneumoniae in pleural fluid. Since then, this organism has played a decisive role in biomedical science. From a biological point of view, it was extensively involved in the development of passive and active immunization by serotherapy and vaccination respectively. Genetic transformation was also first observed in S. pneumoniae, leading to the discovery of DNA. From a clinical point of view, S. pneumoniae is today still a prime cause of otitis media in children and of pneumonia in all age groups, as well as a predominant cause of meningitis and bacteremia. In adults, bacteremia still has a mortality of over 25%. Although S. pneumoniae remained very sensitive to penicillin for many years, penicillin-resistant strains have emerged and increased dramatically over the last 15 years. During this period the frequency of penicillin-resistant isolates has increased from < or = 1% to frequencies varying from 20 to 60% in geographic areas as diverse as South Africa, Spain, France, Hungary, Iceland, Alaska, and numerous regions of the United States and South America. In Switzerland, the current frequency of penicillin-resistant pneumococci ranges between 5 and > or = 10%. The increase in penicillin-resistant pneumococci correlates with the intensive use of beta-lactam antibiotics. The mechanism of resistance is not due to bacterial production of penicillinase but to an alteration of the bacterial target of penicillin, the so-called penicillin-binding proteins. Resistance is subdivided into (1) intermediate level resistance (minimal inhibitory concentration [MIC] of penicillin of 0.1-1 mg/l) and (2) high level resistance (MCI > or = 2 mg/l). The clinical significance of intermediate resistance remains poorly defined. On the other hand, highly resistant strains have been responsible for numerous therapeutic failures, especially in cases of meningitis. Antibiotics recommended against penicillin-resistant pneumococci include cefotaxime, ceftriaxone, imipenem and in some instances vancomycin. However, penicillin-resistant pneumococci tend to present cross-resistances to all the antibiotics of the beta-lactam family and could even become resistant to the last resort drugs mentioned above. Thus, the explosion of resistance to penicillin in pneumococci is a ubiquitous phenomenon which must be fought against by (1) avoiding excessive use of antibiotics, (2) the practice of microbiological sampling of infected foci before treatment, (3) the systematic surveillance of resistance profiles of pneumococci against antibiotics and (4) adequate vaccination of populations at risk.
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PMID:[Antibiotic resistance in pneumococci]. 872 Mar 23

The in vitro and in vivo activities of CS-940, a new 6-fluoro-8-difluoromethoxy quinolone, were compared with those of ciprofloxacin, tosufloxacin, sparfloxacin, and levofloxacin. The in vitro activity of CS-940 against gram-positive bacteria was nearly equal to or greater than those of the other quinolones tested. In particular, CS-940 was two to eight times more active against methicillin-resistant Staphylococcus aureus than the other quinolones, at the MIC at which 90% of the clinical isolates are inhibited. Against gram-negative bacteria, the activity of CS-940 was comparable to or greater than those of tosufloxacin, sparfloxacin, and levofloxacin, while it was lower than that of ciprofloxacin. The activity of CS-940 was largely unaffected by medium, inoculum size, or the addition of horse serum, but it was decreased under acidic conditions, as was also seen with the other quinolones tested. CS-940 showed potent bactericidal activity against S. aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. In oral treatment of mouse systemic infections caused by S. aureus, Streptococcus pneumoniae, Streptococcus pyogenes, E. coli, K. pneumoniae, Serratia marcescens, and P. aeruginosa, CS-940 was more effective than ciprofloxacin, sparfloxacin, and levofloxacin against all strains tested. Against experimental pneumonia with K. pneumoniae in mice, CS-940 was the most effective of all the quinolones tested. These results suggest that CS-940 may be effective in the therapy of various bacterial infections.
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PMID:In vitro and in vivo antibacterial activities of CS-940, a new 6-fluoro-8-difluoromethoxy quinolone. 872 67

The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In this model, doses of penicillin G of 0.6 mg/kg of body weight given six times at 1-h intervals produced effective pulmonary clearance of a penicillin-susceptible strain (penicillin G MIC, 0.015 microgram/ml), while doses of 40 mg/kg given six times at 1-h intervals were required to clear a penicillin-resistant strain (penicillin G MIC, 1 microgram/ml). Imipenem (MIC, 0.25 microgram/ml) was the most active antibiotic tested against the penicillin-resistant strain, with a calculated dose of 0.42 mg/kg given six times at 1-h intervals, resulting in a 2-log decrease in the number of pulmonary bacteria. Comparable effects were seen with vancomycin (MIC, 0.5 microgram/ml), cefotaxime (MIC, 0.5 microgram/ml), and penicillin G at doses of 3.3, 5.5, and 31.0 mg/kg given six times at 1-h intervals, respectively. The pharmacokinetic profile of vancomycin in infected lungs was superior to those of the other antibiotics, especially in regard to the elimination half-life (215.4 min for vancomycin versus 15.0, 14.5, and 14.5 min for penicillin G, cefotaxime, and imipenem, respectively). Both imipenem and vancomycin allowed 90% survival when 40-mg/kg doses were administered twice a day beginning 5 days after infection. Survival rates with penicillin G (160-mg/kg doses) and cefotaxime (40-mg/kg doses) were 40 and 30%, respectively, while no saline-treated mice survived. The present study shows that the CBA/J mouse pneumonia model may be useful for evaluating antibiotic efficacies against penicillin-resistant pneumococcal pneumonia in immunocompetent individuals. Our data suggest that imipenem and vancomycin may be the most active agents against penicillin-resistant S. pneumoniae pneumonia.
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PMID:Noncompromised penicillin-resistant pneumococcal pneumonia CBA/J mouse model and comparative efficacies of antibiotics in this model. 872 30

To assess the carriage of penicillin-resistant pneumococci (PRP) in our local (military) population, we retrospectively reviewed our laboratory isolates from the period of January 1990 through May 1994 and prospectively obtained nasopharyngeal culture specimens from 179 children during January through May 1994. The incidence of PRP increased from 0% of pneumococcal isolates in 1990 to 36.2% by 1994. Fifty-two of 179 subjects (29%) were carriers of S. pneumonia, and 25 (48%) of them carried PRP; 11 (21.7%) of these isolated were highly resistant to penicillin (MIC, > 1.0 microgram/mL), and 14 (26.9%) were intermediately resistant (MIC, 0.1-1.0 micrograms/mL). Exposure to a health care worker was correlated with pneumococcal carriage (P < .007). Frequent courses of antimicrobial treatment correlated both with carriage of pneumococci (P < .009) and with carriage of PRP (P < .0001). In contrast, antimicrobial prophylaxis was protective against carriage of pneumococci (P < .002). We conclude that there is a high proportion of PRP among carriers of pneumococci in our community, as corroborated by the risk in laboratory isolation of PRP. Children who have had frequent antimicrobial courses are at particular risk.
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PMID:Carriage of penicillin-resistant pneumococci in a military population in Washington, DC: risk factors and correlation with clinical isolates. 878 95


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