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

The effect of protein binding in serum of eight cephem antibiotics (ceftazidime, ceftizoxime, cefotiam, cefmetazole, cefpiramide, cefazolin, cefuzonam, ceftriaxone) on their therapeutic efficacies was examined in mice with experimentally induced intraperitoneal infections or pneumonia. The relationship among therapeutic activity, in vitro antibacterial activity, total or free (unbound) levels in serum, and homogenized whole lung levels was investigated. In the intraperitoneal infection caused by Staphylococcus aureus or Klebsiella pneumoniae, the 50% effective doses (ED50s) of the cephem antibiotics correlated with the area under the concentration-time curve (AUC) values of free levels in serum and the MICs but not with those of total levels in serum. A linear relationship was seen between 1/ED50 values and AUC of free levels in serum/MIC values. On the other hand, in mice with pneumonia caused by K. pneumoniae, the number of bacteria in the lung closely correlated with the AUC of the antibiotic concentration in lung tissue. There was a direct correlation between the levels in lung tissue and total levels in serum but not free levels in serum. The cephem antibiotics tested in this study were bound only slightly to homogenates of mouse lung. These results indicate that the effect of protein binding in serum on therapeutic efficacy against intraperitoneal infection differs from that against pulmonary infection.
 ...
PMID:Effect of protein binding in serum on therapeutic efficacy of cephem antibiotics. 159 Jun 85

Mortality and morbidity of nosocomial pneumonia remain high. Successful treatment of pulmonary infections depends on several factors including type of infection, offending pathogen, status of host defences, and adequate choice of antibiotic therapy. The physician's decision should aim at achieving antibiotic concentrations beyond the MIC at the site of infection. Gram-negative bacilli, notably Pseudomonos aeruginosa, Klebsiella pneumoniae and Escherichia coli, remain the most frequent agents in nosocomial pneumonia. Staphylococcus aureus and Streptococcus pneumoniae predominate among the Gram-positive cocci. Pneumocystis carinii predominates in immunocompromised patients. Protected sample bronchoscopy associated with quantitative cultures of samples, and quantification of intracellular microorganisms in cells recovered by broncho-alveolar lavage are two promising procedures which might replace previous, more aggressive methods. Penetration of antibiotics into lung tissue depends on physicochemical properties of the drug and the degree of inflammation of lung tissue. Quinolones, macrolides, tetracyclines and trimethoprim penetrate well into bronchial secretions. Penetration is moderate to low for aminoglycosides and beta-lactams. Fluoroquinolones and new beta-lactam agents, including third-generation cephalosporins imipenem, aztreonam and ticarcillin-clavulanate, showed comparative clinical efficacy in treatment of nosocomial pneumonia, with an efficacy rate close to 80%. Aminoglycosides should not be used alone. Combination therapy reduces but does not eliminate the risk of selection of Gram-negative resistant mutants. It should not be used routinely except for P. aeruginosa, Enterobacter cloacae and Serratia marcescens infections.
 ...
PMID:Drug treatment of pneumonia in the hospital. What are the choices? 172 42

Cefpirome (CPR, HR 810) was clinically evaluated for its efficacy and safety in 11 patients with ages from 4 months to 11 years with bacterial infection. The results obtained are summarized as follows. 1. CPR was administered to 6 patients with bronchopneumonia, a patient with pneumonia, a patient with tonsillitis, 2 patients with acute pharyngitis and a patient with suppurative parotitis at daily dosage levels ranging 55.5-91.7 mg/kg, divided into 3 using intravenous bolus injection or 30 minutes drip infusion. Clinical responses of the 11 patients were as follows: excellent; 8 patients, good; 2 patients, poor; 1 patient, hence the efficacy rate was 90.9%. 2. Neither clinical adverse reaction nor abnormal laboratory test value was observed except slight elevation of GOT and GPT in a patient and leukopenia in another. 3. MICs of CPR against 18 beta-lactamase producing strains isolated from patients were as follows. MIC against a strain of Staphylococcus aureus was 1.56 micrograms/ml, MICs against 3 strains of Klebsiella pneumoniae were less than 0.025 microgram/ml, those against 3 out of 5 strains of Enterobacter cloacae were less than 0.025 microgram/ml and those against the remaining 2 strains were 0.05 and 0.20 micrograms/ml. MICs against 2 out of 3 strains Acinetobacter lwoffi were 1.56 micrograms/ml, and that of the remaining 1 strain was 0.39 microgram/ml. MICs against 2 strains of Pseudomonas cepacia were 1.56 micrograms/ml. MICs against a strain of Pseudomonas putida and a strain of Citrobacter diversus were 0.78 and less than 0.025 microgram/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Clinical evaluation of cefpirome in children]. 188 Sep 23

Cefdinir (CFDN), a newly developed oral cephalosporin in 5% fine granular form, was administered to 10 boys at 1 hour before meal (in the fasting state) and concentrations of the drug in plasma and urine and its urinary recovery rates were determined. The subjects were divided into 2 groups of 5 boys each; one group received 3 mg/kg of CFDN, and the other, 6 mg/kg. To 6 of the 10 children the drug was administered in the two different dose levels using the cross-over method. To study clinical and bacteriological effects of this drug, a mean dose of 4.6 mg/kg t.i.d. was administered for 8 days on the average to 40 children with various infections; pharyngitis (4 cases), tonsillitis (2), acute bronchitis (2), pneumonia (8), scarlet fever (6), acute purulent otitis media (1), urinary tract infection (12), impetigo (2), phlegmon (1), lymphadenitis (1) and subcutaneous abscess (1). MICs were determined for 6 drugs including CFDN, cefaclor, cefixime (CFIX), methicillin, cloxacillin (MCIPC), amoxicillin (AMPC) against 13 strains of 6 species freshly isolated from children receiving CFDN. An inoculum size of 10(6) cfu/ml was used in the MIC-determinations. Adverse reactions and abnormal laboratory findings attributable to this drug were also examined in these patients. The results obtained are summarized as follows. 1. Mean plasma peak levels of CFDN were observed at 3 hours after administration in both the 3 mg/kg and 6 mg/kg groups with mean peak values of 0.68 and 1.35 micrograms/ml, respectively. Mean half-lives were 2.06 hours in the 3 mg/kg group and 1.61 hours in the 6 mg/kg group, and mean AUCs were 3.5 in the former and 6.5 micrograms.hr/ml in the latter. Thus, dose-response between the 2 doses was observed in plasma levels and AUCs. 2. To 3 patients, CFDN was given in the two different doses using the cross-over method. Mean plasma peak levels of CFDN were 0.71 and 1.31 micrograms/ml in the doses of 3 mg/kg and 6 mg/kg, respectively. Half-lives were 1.39-2.90 hours in the 3 mg/kg group and 1.21-1.48 hours in the 6 mg/kg group, with AUCs of 3.4-3.7 and 4.1-7.5 micrograms.hr/ml, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Pharmacokinetics and clinical effects of cefdinir 5% fine granules in pediatrics]. 208 19

A Pseudomonas aeruginosa (isolate 416) from a patient with pneumonia, was initially susceptible to imipenem (MIC: 2 mg/l) but became resistant to this antibiotic (isolate 470, MIC: 32 mg/l) during imipenem therapy. Treatment failed. No parallel increases in MIC were observed for other antimicrobials tested. Isolates 416 and 470 shared the same pyocin type and serotype, produced small amounts of an inducible beta-lactamase, and had similar lipopolysaccharide compositions. On electrophoresis of outer membrane proteins, the porin F, identified by the monoclonal antibody MA4-4, was expressed similarly by the two isolates but the production of one band (apparent molecular weight: 47,000) was diminished in isolate 470. [14C]-Imipenem labelling of intact cells proceeded more slowly in 470 than in 416, especially when bacterial cells were treated by antibody MA4-4 to block the porin F channel. [14C]-Imipenem labelling of penicillin binding proteins (PBP) showed that the band identified as PBP-4 bound markedly less radioactivity in isolate 470 than in 416. After isolate 470 was passaged several times in antibiotic-free broth, the imipenem MIC was decreased from 32 to 8 mg/l, and the [14C]-imipenem PBP pattern recovered the initial profile as exhibited by isolate 416. Two resistance mechanisms, affecting imipenem electively, could have combined their effect in the post-therapy isolate, altered target protein and reduced permeability.
 ...
PMID:Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate. 210 15

Norfloxacin (NFLX, AM-715), a new quinolone antibiotic agent, was evaluated clinically and bacteriologically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows. 1. Incidence of NFLX-resistant strains (MIC over 12.5 micrograms/ml) isolated from children with various infections was 1.6% (8/512). One resistant strain was observed among 45 isolates of Staphylococcus aureus, and none among 30 isolates of Pseudomonas aeruginosa. 2. After single oral administration of 1.5-2.9, 3.0-4.8 and 5.1-6.1 mg/kg NFLX in tablet form at fasting, mean peak values of serum concentration of 0.37, 0.56, 0.92 micrograms/ml, T1/2 of 2.5, 2.6, 2.6 hours and urinary recovery rates in 8 hours at 25.3, 25.3, 27.1% were observed, respectively. 3. Clinical effects were studied chiefly in intestinal and urinary tract infections. Among 317 patients from whom pathogens had been isolated, responses to the treatment were excellent in 187, good in 79, fair in 9, poor in 7, and unknown in 35 cases. The overall efficacy rate was 94.3% (266/282) and the efficacy rate for excellent responses was 70.3% (187/266). Among all the 406 patients treated, including those with undetermined pathogens, responses were excellent in 233, good in 106, fair in 11, poor in 11, and unknown in 45 cases. The overall efficacy rate was 93.9% (339/361). 4. Clinical effects of NFLX classified by diseases with identified pathogens were 81.8% (9/11) for acute pneumonia, 80.8% (21/26) for other respiratory infections, 95.8% (23/24) for bacillary dysentery, 98.6% (70/71) for Campylobacter enteritis, 100% (24/24) for Salmonella enteritis, 100% (6/6) for other acute enteritis and 98.1% (104/106) for urinary tract infections. Including other infections as high as 94.3% (266/282) of efficacy rate was obtained in total. There was no significant difference in NFLX efficacies between unidentified and identified pathogens. Thus, the total clinical efficacy rate was 93.9% (339/361). 5. The total eradication rate of 325 pathogens evaluable was 84.3%, with identical eradication rates for Gram-positive cocci (GPC) (43/51) and for Gram-negative rods (GNR) (231/274). 6. The optimal daily dose of NFLX seemed to be in a range between 6.0 and 12.0 mg/kg, and the optimal duration of treatment to be 7 days for children over 5 years old. 7. The clinical efficacy in treating P. aeruginosa infections in 12 patients was 100% (11/11) and the eradication rate was 83.3% (10/12).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Evaluation of norfloxacin in the pediatric field. Pediatric Study Group for Norfloxacin]. 219 14

We produced experimental murine Klebsiella pneumoniae pneumonia by air-borne infection using exposure apparatus (LD50: 9.7 X 10 C.F.U./lung). The MIC value of cefazolin was 1.56 micrograms/ml, and that of gentamicin was 0.39 micrograms/ml. We treated this murine pneumonia with aerosolized antibiotics. The infected mice received inhalation of 50 mg (5 mg/ml), 100 mg (10 mg/ml), 200 mg (20 mg/ml) and 400 mg (40 mg/ml) gentamicin were alive. Survival rate of the infected mice treated with inhalation of 1000 mg (100 mg/ml) cefazolin was low, but that of them received inhalation of 500 mg (50 mg/ml) cefazolin was high. On the basis of these experiments it is suggested that aerosol of 50 mg/ml cefazolin gets to alveoli, and inhalation therapy of low level of cephems is proper for bacterial respiratory infections. Inhalation therapy of 50 mg/ml cephem for chronic bronchitis had a marked clinical effect. This proves that aerosol of cephem gets to infected bronchi.
 ...
PMID:[Inhalation therapy of antibiotics]. 229 Feb 26

Eighty-three episodes of Gram-positive infection in 82 patients were treated with teicoplanin in an open study. Infectious episodes included endocarditis (6 cases), bacteraemia (7), osteomyelitis (8), pseudomembranous colitis (13), cellulitis (11), urinary tract infection (5), pneumonia (1), wound and post-surgical infections (9) and erysipelas (23). Four patients affected by an overwhelming Gram-positive infection as well as eight cases of Gram-positive-Gram-negative mixed infections received teicoplanin in combination with other antibiotics. The average duration of treatment was 16 days (range 5-70). In pseudomembranous colitis teicoplanin was given by mouth for ten days. Staphylococcus aureus (11 methicillin-sensitive and 13 methicillin-resistant strains) and Clostridium difficile (13 isolates) were the most frequent pathogens. Overall 89% (74/83) of the infections were cured, 3.6% (3/83) improved and 3.6% (3/83) failed. Relapse and superinfection were observed in 2.4% (2/83) and 1.2% (1/83) episodes respectively. All pseudomembranous colitis cases were clinically cured and C. difficile was eradicated in all but one patient. The MIC range, MIC50 and MIC90 (mg/l) of teicoplanin for C. difficile were less than 0.125-0.250, less than 0.125 and 0.250 respectively. Pharmacokinetic studies in patients given a single iv daily maintenance dose of 400 mg showed that the steady-state trough teicoplanin concentrations in serum were reached on day 8. Assays of skin-subcutaneous tissue biopsies showed that teicoplanin penetrated well into these structures. Side effects were observed in six of the 82 treated patients (7.3%) and teicoplanin had to be discontinued in four cases. The results of the study show that teicoplanin is a safe and useful new agent for the treatment of infections caused by Gram-positive organisms, including methicillin-resistant staphylococci and C. difficile.
 ...
PMID:Teicoplanin in the treatment of infections by staphylococci, Clostridium difficile and other gram-positive bacteria. 252 9

A clinical evaluation of clarithromycin (TE-031, A-56268), a newly synthesized macrolide antibiotic, was made for its efficacy and safety in 30 patients with ages ranging from 8 month-old to 12 year- 2 month-old with mycoplasmal and bacterial infections. The obtained results are summarized below. 1. A pharmacokinetic study following oral administration of TE-031 at 10 mg/kg (granule) or 5.5 mg/kg (tablet) resulted in blood concentrations and urinary recovery rates higher than with other macrolides. 2. TE-031 was administered orally to 5 patients with Mycoplasma pneumonia, 21 patients with pneumonia or bronchopneumonia, 2 patients with pertussis and 2 patients with enterocolitis at daily dosages ranging 11.1-31.6 mg/kg divided into 3. Clinical evaluations of these 30 patients were as follows; excellent: 19 patients, good: 11 patients. The efficacy rate was 100%. 3. Neither clinical adverse reaction nor abnormal laboratory data was found in any of these 30 patients. 4. MICs of TE-031 against 10 strains of bacteria isolated from 10 patients with pneumonia or bronchopneumonia were as follows. MICs against 3, 2 and 2 out of 7 strains of Streptococcus pneumoniae were less than 0.025 microgram/ml, 0.05 microgram/ml and 0.10 microgram/ml, respectively. MIC against a strain of Haemophilus influenzae was 3.13 micrograms/ml. MICs of 2 strains of Branhamella catarrhalis were 0.20 microgram/ml. 5. TE-031 is considered to be a new useful and safe antibiotic in pediatric patient with an excellent bactericidal capacity.
 ...
PMID:[Clinical evaluation of clarithromycin in pediatric patients]. 252 47

This paper discusses the evaluation of new macrolides and new quinolones for the treatment of Legionnaires' disease in in vitro susceptibility test, penetration to polynuclear leukocytes and treatment in an animal model. Some kinds of biological response modifier (BRMs) such as granulocyte colony stimulating factor (GCSF), monocyte CSF (M-CSF), GM-CSF, recombinant interleukin-1 (IL-1) and IL-2 were also evaluated. The antimicrobial activity (MIC) of new macrolides to Legionella pneumophila (45 strains) showed the highest activity in TE-031 (Taisho Pharmaceutical Co., Tokyo, Japan) and then rokitamycin (RKM), RU-28965 (Roussel, France), erythromycin (EM), josamycin (JM) in decreasing order of activity. According to the results of the data of cell-penetration and survival rate after treatment of guinea pigs with experimental Legionella pneumonia, the new macrolides such as TE-031, RKM and RU-28965 are expected to be more effective in the treatment of Legionnaires' disease than EM. New quinolones such as ciprofloxatin (CPFX), NY-198 (Hokuriku Pharmaceutical Co., Japan) or T-3262 (Toyama Kagaku Pharmaceutical Co., Toyama Japan) were compared to ofloxacin (OFLX), enoxacin (ENX) or rifampin (RFP) for evaluation. These drugs showed excellent activity against L. pneumophila and good penetration to polynuclear leukocytes. Regarding the treatment of guinea pig with legionella pneumonia, OFLX was the most effective, and NY-198 or T-3262 were more effective than EM treatment. The highest survival rate was obtained with IL-2 in infected guinea pigs. We also observed the efficacy of combined use of IL-2 and HR-8 10 (Horchst FRG) which is a newly developed cephem antibiotic.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Treatment of severe respiratory infection. Legionella pneumonia]. 261 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>