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C Cabellos

Publications and source records attributed to C Cabellos.

At least 19 recordsLinked to original sources
PubMed2002

Experimental study of the efficacy of vancomycin, rifampicin and dexamethasone in the therapy of pneumococcal meningitis.

The object of the study was to assess the efficacy of rifampicin and the combination of rifampicin plus vancomycin in a rabbit model of experimental penicillin-resistant pneumococcal meningitis. We also studied the effect of concomitant dexamethasone on the CSF antibiotic levels and inflammatory parameters. The rabbit model of pneumococcal meningitis was used. Groups of eight rabbits were inoculated with 106 cfu/mL of a cephalosporin-resistant pneumococcal strain (MIC of cefotaxime/ceftriaxone 2 mg/L). Eighteen hours later they were treated with rifampicin 15 mg/kg/day, vancomycin 30 mg/kg/day or both plus minus dexamethasone (0.25 mg/kg/day) for 48 h. Serial CSF samples were withdrawn to carry out bacterial counts, antibiotic concentration and inflammatory parameters. Rifampicin and vancomycin promoted a reduction of >3 log cfu/mL at 6 and 24 h, and cfu were below the level of detection at 48 h. Combination therapy with vancomycin plus rifampicin was not synergic but it had similar efficacy to either antibiotic alone and it was able to reduce bacterial concentration below the level of detection at 48 h. Concomitant use of dexamethasone decreased vancomycin levels when it was used alone (P< 0.05), but not when it was used in combination with rifampicin. Rifampicin alone at 15 mg/kg/day produced a rapid bactericidal effect in this model of penicillin-resistant pneumococcal meningitis. The combination of vancomycin and rifampicin, although not synergic, proved to be equally effective. Using this combination in the clinical setting may allow rifampicin administration without emergence of resistance, and possibly concomitant dexamethasone administration without significant interference with CSF vancomycin levels.

Animals↗
PubMed2002

Efficacy of colistin versus beta-lactams, aminoglycosides, and rifampin as monotherapy in a mouse model of pneumonia caused by multiresistant Acinetobacter baumannii.

The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. We used three strains of A. baumannii corresponding to the main clones (A, D, and E) involved in the outbreaks of our hospital, with different grades of resistance to imipenem (imipenem MICs of 1, 8, and 512 microg/ml, respectively) and to the other antibiotics. The MIC of colistin was 0.5 microg/ml for the three strains. Reduction of log(10) CFU/g in lung bacterial counts, clearance of bacteremia, and survival versus results with controls were used as parameters of efficacy. Imipenem and sulbactam (Deltalung counts: -5.38 and -4.64 log(10) CFU/ml) showed the highest level of bactericidal efficacy in infections by susceptible and even intermediate strains. Tobramycin and rifampin (-4.16 and -5.15 log(10) CFU/ml) provided good results against intermediate or moderately resistant strains, in agreement with killing curves and pharmacodynamics. On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (-2.39 log(10) CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.

Acinetobacter↗
PubMed2001

Relationship between penicillin and cephalosporin resistance of Streptococcus pneumoniae strains and its inflammatory activity in the experimental model of meningitis.

Using a rabbit model of meningitis, we sought to compare the inflammatory activity induced by three pneumococcal strains with different susceptibilities to penicillin and cephalosporins, belonging to the serotypes 3, 6B and 23F at different inoculum sizes. These serotypes are prevalent in Western Europe and are believed to produce a moderate-to-severe cerebrospinal fluid (CSF) inflammatory response. Only minor differences were observed in the inflammatory activity evoked by the three strains in the subarachnoid space, and most were probably related to differences in bacterial counts. Infection by serotype 23F caused secondary bacteremia in all challenged animals. Our findings reinforce the concept that resistant pneumococci are not more virulent, a fact that should be taken into account when evaluating the efficacy of different anti-pneumococcal therapies. However, the frequent induction of secondary bacteremia by the resistant serotype 23F requires further study.

Animals↗
PubMed2000

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Journal Article↗
PubMed2000

Evaluation of combined ceftriaxone and dexamethasone therapy in experimental cephalosporin-resistant pneumococcal meningitis.

The treatment of meningitis caused by strains of Streptococcus pneumoniae with decreased susceptibility to third-generation cephalosporins is an increasingly frequent and difficult problem. In this study a rabbit model of meningitis was used to determine the efficacy of ceftriaxone at different dosages, and to establish the effect of the addition of dexamethasone to the chemotherapeutic regimen. Groups of eight rabbits were inoculated with 10(6) cfu/mL of a cephalosporin- resistant strain of S. pneumoniae (MIC of cefotaxime/ceftriaxone 2 mg/L). Eighteen hours after inoculation, ceftriaxone (50 or 100 mg/kg/day) with or without dexamethasone (0. 25 mg/kg/ day) was administered for a period of 48 h. The ceftriaxone dose of 50 mg/kg/day was not fully effective in this model (therapeutic failure rate 28%). With a dose of 100 mg/kg/day there were no therapeutic failures and all CSF cultures were below the level of detection at 48 h. CSF ceftriaxone concentrations, area under the time-concentration curve and time above the MIC were not significantly different with or without dexamethasone. However, concomitant use of dexamethasone resulted in higher CSF bacterial counts and a higher number of therapeutic failures (57% with the 50 mg/kg/day dose and 28% with the 100 mg/kg/day dose). Increasing doses of ceftriaxone might be an effective mode of therapy for meningitis caused by S. pneumoniae with MIC </= 2 mg/L. However, in contrast to cephalosporin-sensitive cases, in cases caused by ceftriaxone-resistant strains, concomitant use of dexamethasone was associated with a higher failure rate even when a higher dosage of ceftriaxone was used.

Animals↗
PubMed1999

Streptococcal meningitis in adult patients: current epidemiology and clinical spectrum.

Streptococci other than Streptococcus pneumoniae are a rare cause of bacterial meningitis in adults. We report 29 cases of streptococcal meningitis (1977-1997). The patients comprised 19 men and 10 women, with a mean age +/- standard deviation of 47 +/- 18 years. Nine cases were secondary to neurosurgical procedures, seven to brain abscess, five to cerebrospinal fluid pericranial fistula, and three to endocarditis. Causative microorganisms included the following: viridans group streptococci, 20 cases; anaerobic streptococci, 3; Streptococcus agalactiae, 3; Streptococcus bovis, 2; and Streptococcus pyogenes, 1. Four Streptococcus mitis strains showed decreased susceptibility to penicillin (MIC, 0.5-2 microg/mL). Five patients (17%) died. The infection is increasing in the hospital setting. Streptococci resistant to penicillin should be considered in the empirical treatment of nosocomial meningitis. In cases of community-acquired infection, anaerobic streptococci or streptococci of the Streptococcus milleri group should alert the clinician to the presence of an undiagnosed brain abscess, whereas oral streptococci of the viridans group suggest the diagnosis of bacterial endocarditis.

Adolescent↗
PubMed1998

Current usefulness of procaine penicillin in the treatment of pneumococcal pneumonia.

The aim of this study was to determine whether procaine penicillin could be used in the treatment of suspected pneumococcal pneumonia of mild to moderate severity in an area with a high prevalence of penicillin resistance. Forty-nine patients were treated with 1.2 x 10(6) U of i.m. procaine penicillin every 12 h. By intent-to-treat analysis, 40 of 49 patients were cured and no patient died. Streptococcus pneumoniae could be demonstrated in 17 patients; 5 of 17 isolates were resistant to penicillin (MICs 0.25-4 microg/ml). Fifteen of 17 patients were cured with procaine penicillin, one presented allergy, and one was a therapeutic failure. Mean penicillin serum levels were 2.39 +/- 1.16 microg/ml (peak) and 0.61 +/- 0.38 microg/ml (trough). The results suggest that procaine penicillin may still be useful in the empirical therapy of suspected pneumococcal pneumonia.

Adolescent↗
PubMed1998

Impact of antibiotic resistance on chemotherapy for pneumococcal infections.

Over the past three decades, penicillin-resistant pneumococci have emerged worldwide. In addition, penicillin-resistant strains have also decreased susceptibility to other beta-lactams (including cephalosporins) and these strains are often resistant to other antibiotic groups, making the treatment options much more difficult. Nevertheless, the present in vitro definitions of resistance to penicillin and cephalosporins in pneumococci could not be appropriated for all types of pneumococcal infections. Thus, current levels of resistance to penicillin and cephalosporin seem to have little, if any, clinical relevance in nonmeningeal infections (e.g., pneumonia or bacteremia). On the contrary, numerous clinical failures have been reported in patients with pneumococcal meningitis caused by strains with MICs > or = 0.12 microg/ml, and penicillin should never be used in pneumococcal meningitis except when the strain is known to be fully susceptible to this drug. Today, therapy for pneumococcal meningitis should mainly be selected on the basis of susceptibility to cephalosporins, and most patients may currently be treated with high-dose cefotaxime (+/-) vancomycin, depending on the levels of resistance in the patient's geographic area. In this review, we present a practical approach, based on current levels of antibiotic resistance, for treating the most prevalent pneumococcal infections. However, it should be emphasized that the most appropriate antibiotic therapy for infections caused by resistant pneumococci remains controversial, and comparative, randomized studies are urgently needed to clarify the best antibiotic therapy for these infections.

Anti-Bacterial Agents↗
PubMed1996

High doses of cefotaxime in treatment of adult meningitis due to Streptococcus pneumoniae with decreased susceptibilities to broad-spectrum cephalosporins.

We treated nine patients (10 episodes) with meningitis caused by Streptococcus pneumoniae isolates with decreased susceptibilities to broad-spectrum cephalosporins with high doses of cefotaxime (300 mg/kg of body weight per day; maximum dose, 24 g/day). Early adjunctive therapy with dexamethasone was also administered. Cefotaxime MICs were 0.5 (three episodes), 1 (five episodes), and 2 (two episodes) micrograms/ml, and MBCs ranged from 1 to 4 micrograms/ml. Therapy was well tolerated, and all patients experienced prompt clinical improvement. One patient died 8 days after the end of therapy, the central nervous system infection had already been cured, and the remaining patients recovered without relapses.

Adult↗
PubMed1996

[In vitro bactericide activity of different antibiotic combinations to Streptococcus pneumoniae resistant to penicillin and cefotaxime].

BACKGROUND: To determinate the bactericidal activity of vancomycin, rifampicin, cefotaxime, ceftriaxone and their double and triple combinations against penicillin and third generation cephalosporin-resistant. Streptococcus pneumoniae strain. METHODS: A study of the bactericidal activity of antibiotics alone and in combination was performed by killing-curves with fixed concentration of 2 micrograms/ml, equivalent to 1 < MIC for cefotaxime and ceftriaxone, to 8 x MIC for vancomycin and to 32 < MIC for rifampin. RESULTS: Vancomycin was the only antibiotic with bactericidal effect at 6 hours. Cefotaxime had bactericidal effect at 12 hours. Rifampin had no bactericidal effect. The association of vancomycin plus third generation cephalosporins (cefotaxime and ceftriaxone) showed indifferent effect. Rifampin decreased the bactericidal activity of vancomycin at 12 hours, when both were studied in combination, and it demonstrated antagonistic effect in the double and triple combination in which rifampicin was included. CONCLUSIONS: All associations of vancomycin plus third generation cephalosporins were bactericidal effects, but they did no show synergistic effects against penicillin- and third generation cephalosporin S. pneumoniae strain 2349. All combinations with rifampin showed decreased bactericidal activity or antagonistic effects. However, these results may be interpreted with caution because the in vivo experience of an experimental meningitis model in rabbits showed that the associations of vancomycin plus rifampin and vancomycin plus cefotaxime and rifampin were effective combinations. More in vivo and in vitro comparative studies are needed to demonstrate the reliability of in vitro results.

Adult↗
PubMed1995

Penetration of the blood-brain barrier: enhancement of drug delivery and imaging by bacterial glycopeptides.

The blood-brain barrier restricts the passage of many pharmacological agents into the brain parenchyma. Bacterial glycopeptides induce enhanced blood-brain barrier permeability when they are present in the subarachnoid space during meningitis. By presenting such glycopeptides intravenously, blood-brain barrier permeability in rabbits was enhanced in a reversible time- and dose-dependent manner to agents < or = 20 kD in size. Therapeutic application of this bioactivity was evident as enhanced penetration of the antibiotic penicillin and the magnetic resonance imaging contrast agent gadolinium-diethylene-triamine-pentaacetic acid into the brain parenchyma.

Animals↗
PubMed1995

Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain.

BACKGROUND: Penicillin-resistant strains of Streptococcus pneumoniae are now found worldwide, and strains with resistance to cephalosporin are being reported. The appropriate antibiotic therapy for pneumococcal pneumonia due to resistant strains remains controversial. METHODS: To examine the effect of resistance to penicillin and cephalosporin on mortality, we conducted a 10-year, prospective study in Barcelona of 504 adults with culture-proved pneumococcal pneumonia. RESULTS: Among the 504 patients, 145 (29 percent) had penicillin-resistant strains of S. pneumoniae (minimal inhibitory concentration [MIC] of penicillin G, 0.12 to 4.0 micrograms per milliliter), and 31 patients (6 percent) had cephalosporin-resistant strains (MIC of ceftriaxone or cefotaxime, 1.0 to 4.0 micrograms per milliliter). Mortality was 38 percent in patients with penicillin-resistant strains, as compared with 24 percent in patients with penicillin-sensitive strains (P = 0.001). However, after the exclusion of patients with polymicrobial pneumonia and adjustment for other predictors of mortality, the odds ratio for mortality in patients with penicillin-resistant strains was 1.0 (95 percent confidence interval, 0.5 to 1.9; P = 0.84). Among patients treated with penicillin G or ampicillin, the mortality was 25 percent in the 24 with penicillin-resistant strains and 19 percent in the 126 with penicillin-sensitive strains (P = 0.51). Among patients treated with ceftriaxone or cefotaxime, the mortality was 22 percent in the 59 with penicillin-resistant strains and 25 percent in the 127 with penicillin-sensitive strains (P = 0.64) The frequency of resistance to cephalosporin increased from 2 percent in 1984-1988 to 9 percent in 1989-1993 (P = 0.002). Mortality was 26 percent in patients with cephalosporin-resistant S. pneumoniae and 28 percent in patients with susceptible organisms (P = 0.89). Among patients treated with ceftriaxone or cefotaxime, mortality was 22 percent in the 18 with cephalosporin-resistant strains and 24 percent in the 168 with cephalosporin-sensitive organisms (P = 0.64). CONCLUSIONS: Current levels of resistance to penicillin and cephalosporin by S. pneumoniae are not associated with increased mortality in patients with pneumococcal pneumonia. Hence, these antibiotics remain the therapy of choice for this disease.

Adult↗
PubMed1995

A single daily dose of ceftriaxone for bacterial meningitis in adults: experience with 84 patients and review of the literature.

Although the pharmacokinetics of ceftriaxone allows its administration in a single daily dose, this practice is not standard in the treatment of bacterial meningitis. Herein, we review our experience and that of other investigators with this mode of therapy. We used a single daily dose of ceftriaxone (50 mg/[kg.d]; maximum, 4 g/d) for the treatment of bacterial meningitis in 84 adult patients. Meningitis was due to Neisseria meningitidis in 34 cases, to Streptococcus pneumoniae in 25, to Escherichia coli in three, to Klebsiella pneumoniae in two, to Haemophilus influenzae in two, to viridans streptococci in two, and to an unknown agent in 16. Eleven patients died, for an overall mortality of 13%; therapy failed in three additional cases. The mean trough levels of ceftriaxone in cerebrospinal fluid was 3.5 micrograms/mL; the median trough bactericidal titer at this site was 1:128. Both our experience and that in the literature suggest that a single daily dose is optimal when ceftriaxone is used for the treatment of bacterial meningitis.

Adolescent↗
PubMed1995

The impact of dexamethasone on hearing loss in experimental pneumococcal meningitis.

Bacterial meningitis, particularly that resulting from Streptococcus pneumoniae, is a common cause of acquired profound sensorineural deafness in children. The pathogenesis of meningogenic hearing loss has been investigated in an experimental rabbit model. In this study significant deafness was documented within the first 15 hours of infection. Initiation of antibiotic therapy at this time diminished the severity of hearing loss in most animals. The addition of dexamethasone to antibiotic therapy prevented the development of profound deafness. These results suggest this model will be useful in developing antiinflammatory strategies to improve the outcome of bacterial meningitis.

Animals↗
PubMed1995

Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in experimental pneumococcal meningitis.

Using a rabbit model of meningitis, we sought to determine whether concomitant use of dexamethasone affects the penetration and efficacy of ceftriaxone or vancomycin in cerebrospinal fluid. Rabbits were inoculated with a penicillin-sensitive strain of Streptococcus pneumoniae and treated with ceftriaxone or vancomycin with or without dexamethasone. In the ceftriaxone-treated groups, no statistically significant differences were seen between the group treated with dexamethasone and that without dexamethasone; however, in the vancomycin-treated groups we found statistically significant lower cerebrospinal fluid vancomycin levels at 2 h in the dexamethasone-treated rabbits and differences in bacterial killing.

Animals↗
PubMed1995

Hypersensitivity hepatitis due to pyrazinamide.

Pyrazinamide hepatotoxicity is considered secondary to a direct and dose-related toxic effect. At currently used doses, pyrazinamide provides effective short-term treatment and is free from serious side effects. We report a case of pyrazinamide-induced hepatitis for which the rechallenge data strongly suggest a hypersensitivity mechanism.

Acute Disease↗
PubMed1995

[Protective effect of dexamethasone and phenytoin in the treatment of experimental pneumococcal meningitis].

BACKGROUND: Pneumococcal meningitis has a high morbidity and mortality rate despite effective antibiotherapy, probably due to an exaggerated inflammatory response of the CNS. The use of dexamethasone and phenytoin reduced mortality in adults with pneumococcal meningitis. OBJECTIVE: We sought to determine the effect of dexamethasone, phenytoin or the association of both in several inflammatory parameters in experimental bacterial meningitis. METHODS: The study was performed using a modification of the rabbit model of Dacey and Sande. New Zealand white rabbits were intracisteranly inoculated simultaneously with heat-killed S. pneumoniae R6 dexamethasone, phenytoin or both. CSF leucocytes and concentration of proteins and lactate were determined over 6 hours, as well as the presence of brain edema. RESULTS: Treatment with dexamethasone alone or in association with phenytoin reduced all inflammatory parameters. The administration of phenytoin alone did not prevent an increase of CSF leucocytes or protein concentration, but did prevent the development of brain edema. A trend to wards a protective effect on the lactate concentration was observed. CONCLUSIONS: Our results gives support to the antiinflammatory effect of dexamethasone in experimental pneumococcal meningitis, and suggest that phenytoin may have also a protective effect on brain ischemia. This protective action and the prevention of brain edema could contribute, beyond its anticonvulsivant properties, to the great reduction in the mortality rate observed in some clinical studies in patients with pneumococcal meningitis.

Animals↗