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Biomedical subjects

C Carbon

Publications and source records attributed to C Carbon.

At least 127 records · Page 7Linked to original sources
PubMed1996

Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

Animals↗
PubMed1996

Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media.

Animals↗
PubMed1996

Efficacy of sparfloxacin and autoradiographic diffusion pattern of [14C]Sparfloxacin in experimental Staphylococcus aureus joint prosthesis infection.

Using a new rabbit model of methicillin-susceptible Staphylococcus aureus knee prosthesis infection, we compared the efficacies of sparfloxacin (50 mg/kg of body weight subcutaneously, twice a day) and pefloxacin (50 mg/kg subcutaneously, twice a day). A partial knee replacement was performed with a silicone implant fitted into the intramedullary canal of the tibia, and 5 x 10(7) CFU of methicillin-susceptible S. aureus was injected into the knee. The 7-day treatment regimen was started 15 days later. The MICs and MBCs of sparfloxacin and pefloxacin were, respectively, 0.06 and 0.25 microgram/ml (MIC) and 0.25 and 1 microgram/ml (MBC). The peak levels of sparfloxacin and pefloxacin in serum were 3.6 and 21 micrograms/ml, respectively. Three weeks after the end of treatment, animals were sacrificed and tibias were removed, pulverized, and quantitatively cultured. In contrast to pefloxacin (3.61 +/- 1.64 log10 CFU/g of bone), sparfloxacin significantly reduced the bacterial density (2.12 +/- 1.1 log10 CFU/g of bone) (P = 0.01) in comparison with the level in controls (4.59 +/- 1.21 log10 CFU/g of bone), without selection of resistant variants. Sparfloxacin was significantly more effective than pefloxacin (P = 0.025). The autoradiographic pattern of [14C]sparfloxacin diffusion was studied in noninfected animals with prostheses and in infected animals 15 days after inoculation. Sixty minutes after completion of infusion of 250 microCi of [14C]sparfloxacin, in infected animals the highest levels of radioactivity were detected around the prosthesis, in femoral cartilage, and in articular ligaments. Radioactivity was slightly less intense in bone marrow and muscles and was very weak in compact bone. The distribution of sparfloxacin in uninfected rabbits was similar. Thus, sparfloxacin may represent a valid alternative therapy in these infections provided that it is carefully monitored for potential side effects.

Animals↗
PubMed1996

Intestinal elimination of ofloxacin enantiomers in the rat: evidence of a carrier-mediated process.

The aim of this work was to examine the mechanism involved in intestinal elimination of the two optical isomers of ofloxacin in the rat. An intestinal segment was isolated in situ and perfused with saline, while drug solution was administered via the carotid artery. Blood samples and intestinal effluents were collected and analyzed by a high-performance liquid chromatography method. We observed saturable and stereoselective intestinal elimination of the ofloxacin enantiomers. The elimination process favored the R-(+) form of the molecule. After a parenteral dose of 20 mg of racemic ofloxacin per kg of body weight, intestinal clearances were 0.23 +/- 0.03 versus 0.30 +/- 0.03 ml/min for S-(-)- and R-(+)-ofloxacin, respectively. Ciprofloxacin and pefloxacin interfered with ofloxacin elimination and significantly reduced the intestinal clearance of S-(-)- and R-(+)-ofloxacin. With concomitant ciprofloxacin, intestinal clearances became 0.13 +/- 0.02 versus 0.17 +/- 0.03 ml/min and 0.14 +/- 0.01 versus 0.19 +/- 0.05 ml/min with pefloxacin for S-(-)- and R-(+)-ofloxacin, respectively. Those findings argue for the presence of a common transport system in the rat intestine with variable affinities for fluoroquinolones. In addition, verapamil and quinidine, two P-glycoprotein blockers, significantly reduced the intestinal elimination of both ofloxacin isomers (with concomitant verapamil, intestinal clearances were 0.12 +/- 0.02 versus 0.18 +/- 0.03 ml/min for S-(-)- and R-(+)-ofloxacin, respectively, while with concomitant quinidine, values were 0.18 +/- 0.01 versus 0.23 +/- 0.01 ml/min without modifying their areas under the concentration-time curve in serum. Similar results were found with another fluoroquinolone, ciprofloxacin, in previous work. P-glycoprotein appears to be involved in the intestinal elimination of fluoroquinolones in rats. The characterization of fluoroquinolone intestinal elimination has significant clinical relevance for the better evaluation of the influence of this secretory pathway on antibiotic efficacy and selection of resistant bacteria within the intestinal flora.

Animals↗
PubMed1996

Synergy between amoxicillin and gentamicin in combination against a highly penicillin-resistant and -tolerant strain of Streptococcus pneumoniae in a mouse pneumonia model.

In vivo synergy with beta-lactam antibiotics and aminoglycosides has been studied only with penicillin-susceptible Streptococcus pneumoniae strains. We evaluated the interaction between amoxicillin (AMX) and gentamicin (GEN) on the basis of in vitro checkerboard and time-kill curves and of findings in a mouse model of acute bacteremic pneumonia due to a highly penicillin-resistant and -tolerant S. pneumoniae strain of serotype 19 (penicillin and AMX MICs of 4 micrograms/ml; gentamicin MIC of 16 micrograms/ml). Checkerboard results at 18 h of incubation showed indifference. With regard to AMX alone, in vitro time-kill curves demonstrated synergy between AMX (1 microgram/ml) and GEN (16 micrograms/ml) at 5 and 8 h of incubation and for AMX (16 micrograms/ml) in combination with GEN (16 micrograms/ml) at 3, 5, and 8 h of incubation. In leukopenic mice, pulmonary killing curves after a single drug injection demonstrated that AMX (100 mg/kg of body weight) with GEN (16 mg/kg) was more effective than AMX alone (P = 10(-4). With repeated-dose treatment, a synergy was apparent at 8 h after four injections with AMX (100 mg/kg) in combination with GEN (8 or 16 mg/kg) (P < or = 0.05). The cumulative survival rate with AMX (100 mg/kg) every 8 h, combined with GEN (4 or 8 mg/kg) every 8, 12, or 24 h, was better than with AMX alone. Combined use of AMX and GEN may be a valuable therapeutic alternative for pneumococcal pneumonia due to highly penicillin-resistant S. pneumoniae strains.

Amoxicillin↗
PubMed1996

[Digestive sites disclosing sarcoidosis].

We report two cases of gastrointestinal sarcoidosis. One patient had a gastric involvement, the other a duodenal and ileum involvement. The two patients had the same symptoms, including diarrhea, vomiting, abdominal pain and weight loss. Endoscopic examination revealed only an erythematous gastritis in the first patient, while the colon and the small bowel were macroscopically normal in the second. Histologic findings were consistent with a gastric and salivary gland sarcoidosis granulomata for the first patient and with a lung, duodenal and small intestine involvement for the second one. Gastrointestinal involvement in sarcoidosis is rare, especially small bowel localization. A brief discussion and a literature review of gastrointestinal sarcoidosis are presented.

Adult↗
PubMed1995

[Pneumococcal septic arthritis in HIV infection].

Infections due to pneumococci are frequent in patients infected with the human immunodeficiency virus (HIV), but joint infections are rare. We observed two cases of septic arthritis due to pneumococci in two non-haemophilic HIV seropositive patients. In the first case, a 31-year old drug addict who had undergone splenectomy, developed hip joint infection during an episode of meningitis due to pneumococci. The germ was moderately sensitive to ampicillin. The second case involved the knee joint in a 29-year-old woman who developed pneumococcal pneumonia after a trip to Zaire. In both cases, joint infection developed after antibiotics had been initiated, and in the first case, after the infection appear to be under control. This would be similar to "post-infectious" arthritis described in gonococcal and meningococcal infections. In HIV positive patients, joint infections are rare compared with other types of immunodepression, but can be observed in all stages of the disease. A total of 75 cases have been reported in the literature, including 8 cases due to pneumococci. These joint infections could be another argument in favour of anti-pneumococcal vaccination in HIV positive patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Clinical relevance of intracellular and extracellular concentrations of macrolides.

The serum levels of the three macrolides--roxithromycin, clarithromycin and azithromycin--vary considerably. The prediction of the antibacterial effect against extracellular pathogens is based on circulating concentrations of free drug, peak and trough levels, the rate of killing, and the presence of a post-antibiotic effect. Intracellular activity depends on the distribution of the antibiotic and the localization of the bacteria, and is variable. Roxithromycin uptake is greater than that of erythromycin. The intracellular half-life may be long for some compounds (azithromycin > roxithromycin). The intracellular distribution is bimodal, both in the lysosomes and the cytoplasm, but the mechanisms of uptake have not yet been established. At low pH, accumulation is low and macrolides are less active in an acidic medium. Intracellular concentrations cannot readily be predicted on the basis of extracellular levels. Different models have shown that the greater the intracellular concentration, the better the clinical effect. In addition, the transport of macrolides by cells into the infected focus may play an important role in the therapeutic outcome. These factors influence the clinical indications for macrolides, their dosing regimens and breakpoints. In future, macrolides will be developed that are more selective for intracellular infections, while others, which will achieve significant serum levels, will be useful for a broader range of diseases. However, new compounds should be evaluated in different models of infection before clinical studies are instituted. The analysis of failures remains the most important approach in defining concentration/effect relationships.

Animals↗
PubMed1995

Amoxicillin intestinal absorption reduction by amiloride: possible role of the Na(+) -H+ exchanger.

Intestinal absorption of beta-lactam antibiotics has been shown to use the dipeptide carrier system. In vitro experiments have established that the efficiency of uptake by enterocytes depends on an inwardly directed proton gradient--dipeptides and beta-lactam antibiotics being cotransported along with hydrogen ion. This gradient is thought to result from the sodium-hydrogen (Na(+)-H+) exchanger located on the brush-border membrane. The aim of the present study was to assess the in vivo relevance of these data in humans by examining the effect of amiloride, a well-known inhibitor of the Na(+) -H+ exchanger, on the bioavailability of amoxicillin in eight healthy volunteers. The results show that amiloride reduces significantly amoxicillin absorption rate (mean time to maximum concentration increases from 1.0 to 1.6 hours, p < 0.05) and absolute bioavailability (by 27%, p < 0.01) and that amiloride-induced inhibition of the intestinal Na(+) -H+ exchange could be associated with an additional inhibitory effect on (Na/K)-ATPase activity. The present data seem to confirm the role of Na(+) -H+ exchange in the uptake of beta-lactams by the intestine and to support the indirect sodium dependence of this carrier system in vivo.

Adult↗
PubMed1995

Acute and chronic bronchitis.

Although questions persist on the precise role of infection in acute exacerbations of chronic bronchitis and on the overall benefit of antibiotic therapy of acute episodes, antibiotic therapy is considered an important part of the management of patients. It has to obey precise rules and obviously must be associated with preventive measures that can help to reduce both frequency and severity of acute exacerbations. The modifications of the susceptibility pattern to antibiotics of the two main bacteria involved deserve special attention to control the extension of the problem and define new therapeutic strategies. At present the currently recommended regimens are still valuable.

Acute Disease↗
PubMed1995

Systemic prophylaxis of experimental staphylococcal endophthalmitis: comparative efficacy of sparfloxacin, pefloxacin, imipenem, vancomycin, and amikacin.

The preventive efficacy of several antibiotics in experimental staphylococcal endophthalmitis was evaluated. Two hours before bilateral intravitreal infection with 500 cfu of Staphylococcus aureus, 18 pigmented phakic rabbits were assigned to receive a single intramuscular injection of sparfloxacin (50 mg/kg), pefloxacin (50 mg/kg), imipenem (50 mg/kg), vancomycin (30 mg/kg), amikacin (15 mg/kg), or saline and were killed 24 h after infection (6 eyes/group). Sparfloxacin, pefloxacin, and imipenem were significantly (P < .001) more effective than saline. All but 1 of the sparfloxacin-treated eyes were culture negative. To determine whether the effect persisted, an additional 24 rabbits were treated with sparfloxacin, pefloxacin, imipenem, or saline and were killed 48 h after infection (12 eyes/group). Sparfloxacin, pefloxacin, and imipenem were effective (P < .001). All sparfloxacin-treated eyes remained culture negative. These results show that systemic antibiotic administration prevents the development of experimental endophthalmitis and that further studies of sparfloxacin as a prophylactic agent are warranted.

Amikacin↗
PubMed1995

A double-blind randomized trial comparing the efficacy and safety of a 5-day course of cefotiam hexetil with that of a 10-day course of penicillin V in adult patients with pharyngitis caused by group A beta-haemolytic streptococci.

A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Activity of CI-960 alone and in combination with amoxycillin against Listeria monocytogenes, and comparison with other quinolones.

In-vitro activity of CI-960 against seven strains of Listeria monocytogenes was compared to that of other fluoroquinolones. MICs/MBCs were: ciprofloxacin and sparfloxacin: 0.5-2/1-4 mg/L;PD 131628: 0.125-0.5/0.25-2 mg/L; CI-960: 0.06-0.25/0.25-0.5 mg/L. At 4 h, CI-960 (4 x MIC) reduced the inoculum (log10 cfu) by 2.88 +/- 0.61 compared with 1.78 +/- 0.48 for ciprofloxacin, 1.5 +/- 0.46 for sparfloxacin, and 1.35 +/- 0.47 for PD 131628 (P < 0.05). At 24 h, the bactericidal effects were similar (-4 log10 cfu). The amoxycillin/CI-960 (8 x MIC) combination was bactericidal, without emergence of resistant mutants.

Amoxicillin↗
PubMed1995

Intestinal elimination of sparfloxacin, fleroxacin, and ciprofloxacin in rats.

The intestinal transepithelial elimination of sparfloxacin and fleroxacin was compared with that of ciprofloxacin in a rat model following a single parenteral administration of 25 mg of each of the antibiotics per kg of body weight. All three fluoroquinolones were eliminated through the small intestine. Ciprofloxacin was eliminated in the proximal jejunum at a rate of 1.97 +/- 0.70 micrograms/cm2, while the elimination rates of fleroxacin and sparfloxacin were 0.64 +/- 026 and 0.21 +/- 0.10 micrograms/cm2, respectively, over a 90-min collection period. In the ileum, the elimination rates of ciprofloxacin, fleroxacin, and sparfloxacin over the same period were 1.44 +/- 0.77, 1.00 +/- 0.33, and 0.41 +/- 0.26 micrograms/mc2, respectively. These data suggest that these fluoroquinolones undergo a transepithelial elimination process in the small intestine. This route of elimination may be important in the therapy of bacterial diarrhea.

Animals↗
PubMed1995

Critical influence of timing of administration of granulocyte colony-stimulating factor on antibacterial effect in experimental endocarditis due to Pseudomonas aeruginosa.

The effect of human recombinant granulocyte colony-stimulating factor (hrG-CSF) in rabbits with aortic endocarditis due to Pseudomonas aeruginosa was investigated. hrG-CSF significantly increased the number of polymorphonuclear neutrophils in blood and in cardiac vegetations and the expression of the adhesin molecule CD11b on the surface of polymorphonuclear neutrophils compared with those of animals that had not received hrG-CSF. When treatment was started 72 h after bacterial challenge, hrG-CSF alone had no antibacterial effect and did not enhance the efficacy of ciprofloxacin when used in combination, even with the higher dosing regimen used (50 micrograms/kg of body weight subcutaneously every 12 h for 4 days), in terms of number of positive blood cultures, bacterial counts in vegetations, and survival. In contrast, when treatment was started 30 min prior to bacterial challenge, hrG-CSF (50 micrograms/kg injected every 12 h) decreased bacterial titers in vegetations 72 h later (6.5 +/- 0.9 versus 7.9 +/- 0.9 log10 CFU/g of vegetation for hrG-CSF and controls, respectively; P = prophylactic administration of hrG-CSF did not increase the antibacterial effect of ciprofloxacin. We concluded that the antibacterial effect of hrG-CSF in experimental endocarditis was related to the timing of its administration since hrG-CSF demonstrated a significant but transient antimicrobial effect only when treatment was initiated before bacterial challenge.

Animals↗
PubMed1995

Critical influence of resistance to streptogramin B-type antibiotics on activity of RP 59500 (quinupristin-dalfopristin) in experimental endocarditis due to Staphylococcus aureus.

In order to determine the microbiological and pharmacokinetic parameters that best predicted the in vivo antistaphylococcal activity of the streptogramin RP 59500 (quinupristin-dalfopristin), we evaluated the activity in rabbit aortic endocarditis of three regimens of quinupristin-dalfopristin against five strains of Staphylococcus aureus with various streptogramin B-type antibiotic resistance phenotypes and susceptible to streptogramin A-type antibiotics. Quinupristin-dalfopristin was as active as vancomycin against three strains that were susceptible to its streptogramin B component quinupristin, including one strain that was inducibly resistant to erythromycin, but had a significantly decreased activity against two strains that were resistant to quinupristin, for all quinupristin-dalfopristin regimens tested (P < 0.05). The area under the concentration-time curve for quinupristin-dalfopristin in plasma divided by the MIC of quinupristin was the only parameter retained by multilinear regression that predicted the in vivo activity of quinupristin-dalfopristin (P = 0.0001), emphasizing the importance of determining the susceptibility to quinupristin in order to predict the in vivo activity of quinupristin-dalfopristin against S. aureus.

Animals↗
PubMed1995

Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the dexamethasone-treated rat model.

In the dexamethasone-treated rat model of cryptosporidiosis, paromomycin was effective at a dosage of 50 mg/kg/day or more for ileal infection and 200 mg/kg/day or more for cecal infection. At 1 and 3 weeks after treatment, a persistent infection was demonstrated in all rats. These results confirm the anticryptosporidial activity of paromomycin and underscore the limitations of this compound because of its potential toxicity at such high dosages and its inability to eradicate the infection.

Animals↗