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J Liñares

Publications and source records attributed to J Liñares.

At least 19 recordsLinked to original sources

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

Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin.

The in vitro antibacterial activity of FK-037, a new parenteral cephalosporin structurally related to cefpirome and cefepime, was compared with that of cefotaxime, ceftazidime, aztreonam, cefpirome, cefepime, imipenem and meropenem against 1,837 clinical isolates obtained from three Spanish hospitals. FK-037 inhibited 90% of Enterobacteriaceae isolates at < or = 0.25 microgram/ml, with the exception of Enterobacter aerogenes (MIC90 1 microgram/ml), Enterobacter cloacae and Citrobacter freundii (MIC90 8 micrograms/ml). In cefotaxime- and ceftazidime-resistant Klebsiella pneumoniae strains producing SHV-2 and SHV-6 beta-lactamases, the activity of FK-037, cefpirome and cefepime was similar (MIC range 0.25-32 micrograms/ml). In Enterobacteriaceae strains hyper-producing chromosomally inducible beta-lactamases, FK-037 (MIC90 range, 0.25-8 micrograms/ml) was 8- to 16-fold more active than cefotaxime and ceftazidime but two- to eightfold less active than cefpirome and cefepime. FK-037 and cefpirome were twofold more active than ceftazidime and cefepime against Pseudomonas aeruginosa isolates, with MIC90 values of 16 micrograms/ml. The activity of FK-037, cefpirome and cefepime was two- to eightfold lower in ceftazidime-resistant derepressed Pseudomonas aeruginosa mutants. FK-037 (MIC range, 0.12-2 micrograms/ml) and the other beta-lactam agents tested were active against methicillin-susceptible staphylococci; however, only cefpirome and, particularly, FK-037 (MIC90 of 32 micrograms/ml) displayed some activity against methicillin-resistant strains. In penicillin-susceptible, -intermediate and -resistant Streptococcus pneumoniae isolates, the MIC90s of FK-037 were 0.03, 0.5 and 1 microgram/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aztreonam

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

[Thoracic actinomycosis].

BACKGROUND: Thoracic actinomycosis is an rare disease in our medium. This fact, together with the variability of its forms of presentation and the difficulty in isolating its etiologic agent, make its diagnosis, particularly difficult. METHODS: A series of 8 cases diagnosed in the years 1988, 1989 and 1990 in two centers (Hospital de Bellvitge-Prínceps d'Espanya and Hospital de l'Esperança) is described with evaluation of the clinical and analytical data and the therapy applied. RESULTS: Species were only identified in 3 cases with Actinomyces israelii in two and Actinomyces odontolyticus in the third. The proven association with Mycobacterium tuberculosis, the presence of distant septic metastasis and eosinophilic pleuritis as forms of presentation are of note. Medical treatment was penicillin or derivatives in all the cases except one which was treated with diagnostic/therapeutic segmentectomy. CONCLUSIONS: It is concluded that when any subacute involvement of the thoracic and/or pleuropulmonary wall specific cultures should be carried out to discard eventual thoracic actinomycosis.

Actinomyces

In vitro activity of azithromycin and tetracycline against 358 clinical isolates of Brucella melitensis.

The in vitro activity of azithromycin against human pathogenic strains of Brucella melitensis was tested at three centres and compared to that of tetracycline, the standard antibiotic currently used for the treatment of human brucellosis. MIC determination was carried out. Tested concentration ranges for both azithromycin and tetracycline were between 0.03 and 16 micrograms/ml. Brucella melitensis biotype 1, strain M16 was employed as a control microorganism. A total of 358 Brucella melitensis strains from human blood cultures were tested. MIC90 (micrograms/ml) values ranged from 0.5 to 1.00 for azithromycin and were 0.25 for tetracycline. It was concluded that there was little difference in the sensitivity of pathogenic Brucella melitensis to azithromycin and tetracycline isolated from three different regions in Spain. These results encourage further investigations on the possible therapeutic role of azithromycin in brucellosis.

Azithromycin

Trends in antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in Bellvitge Hospital, Barcelona, Spain (1979-1990).

From January 1979 to December 1990 we studied the susceptibility of 1,492 pneumococcal strains isolated from adult patients in Bellvitge Hospital, Barcelona, Spain, to nine antimicrobial agents. Among clinically significant pneumococci, the incidence of penicillin-resistant strains increased from 4.3% in 1979 to 40% in 1990, and that of erythromycin-resistant strains also rose from 0% in 1979 to 9.4% in 1990. On the other hand, the incidence of strains resistant to tetracycline decreased from 76.1% to 37.6%, as did that of chloramphenicol-resistant strains, from 56.5% to 29.4%. The incidence of co-trimoxazole-resistant strains was about 40% throughout the study. Even more alarming was the finding that about 70% of penicillin-resistant strains showed multiple resistance to non-beta-lactam antibiotics. All pneumococci were susceptible to vancomycin, and all but six were susceptible to rifampin. We observed that isolates from cerebrospinal fluid and the respiratory tract were significantly more resistant to penicillin than were isolates from blood. The majority of strains (95%) belonged to serogroups or serotypes included in the 23-valent pneumococcal vaccine and 77.6% of penicillin-resistant strains belonged to groups 23, 6, 9, and 19.

Adult

Decreased susceptibility of penicillin-resistant pneumococci to twenty-four beta-lactam antibiotics.

The in-vitro activity of 24 beta-lactam antibiotics was compared using three groups of pneumococci and an agar dilution method comprising 100 penicillin-susceptible, 100 intermediately penicillin-resistant, and 100 highly penicillin-resistant pneumococcal strains. Our results show that intermediately penicillin-resistant and highly penicillin-resistant pneumococci had decreased sensitivity to other beta-lactam agents. According to their relative in-vitro activity, the antimicrobials were classified into three groups. The first group included drugs more active than penicillin (imipenem, meropenem, cefotaxime, ceftriaxone, and cefpirome), which could be useful for the treatment of infections due to penicillin-resistant strains. The second group showed slightly lesser activity than did penicillin, and included: ampicillin, cefdinir, cefuroxime, cefoperazone, azlocillin, mezlocillin, piperacillin, cephalothin, and cefamandole. The remaining antibiotics (oxacillin, cefixime, ceftizoxime, cefetamet, cefaclor, ceftazidime, cefoxitin, cefonicid, and latamoxef) showed poor activity against penicillin-resistant strains, precluding their use for empirical treatment in areas with a high prevalence of penicillin-resistant strains.

Anti-Bacterial Agents

Aztreonam vs. cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients.

Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis. Patients were randomized into two therapeutic groups of similar characteristics. Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period. Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms. Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group. In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure. Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment. The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS). Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment. Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group. We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection. Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population.

Adult

Evaluation of vancomycin for therapy of adult pneumococcal meningitis.

The emergence of pneumococci resistant to penicillin and other agents prompted us to evaluate intravenous vancomycin for the therapy of pneumococcal meningitis, which has an overall mortality of 30%. Eleven consecutive adult patients with cerebrospinal fluid (CSF)-culture-proven pneumococcal meningitis and positive initial CSF Gram stain were given intravenous vancomycin (usual dosage, 7.5 mg/kg every 6 h for 10 days). The MBCs of vancomycin ranged from 0.25 to 0.5 micrograms/ml. Early adjunctive therapy with intravenous dexamethasone, mannitol, and sodium phenytoin was also instituted. After 48 h of therapy, all 11 patients showed a satisfactory clinical response, although the CSF culture remained positive in one case; median trough CSF and serum vancomycin levels were 2 and 5.1 micrograms/ml, respectively, and trough CSF bactericidal titers ranged from less than 1:2 to 1:16. On day 3, one patient died of acute heart failure. Four patients had clinical failure at on days 4 (two patients), 7 (one), and 8 (one) of therapy; they all immediately responded to a change in antibiotic therapy. The remaining six patients were cured after 10 days of vancomycin therapy. At this point, median peak CSF and serum vancomycin levels were 1.9 and 18.5 micrograms/ml, respectively. A transient alteration of renal function occurred in two patients, and persistent slight hypoacusia occurred in three patients. In summary, 11 adults with pneumococcal meningitis were treated with vancomycin and early adjunctive therapy including dexamethasone. All patients initially improved, and 10 were ultimately cured of the infection. However, four patients experienced a therapeutic failure, which led to a change in vancomycin therapy.

Adolescent

Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae.

Resistance to penicillin in clinical isolates of Streptococcus pneumoniae has occurred by the development of altered penicillin-binding proteins (PBPs) that have greatly decreased affinity for the antibiotic. We have investigated the origins of penicillin-resistant strains by comparing the sequences of the transpeptidase domain of PBP2B from 6 penicillin-sensitive and 14 penicillin-resistant strains. In addition we have sequenced part of the amylomaltase gene from 2 of the sensitive and 6 of the resistant strains. The sequences of the amylomaltase gene of all of the strains and of the PBP2B gene of the penicillin-sensitive strain show that S. pneumoniae is genetically very uniform. In contrast the PBP2B genes of the penicillin-resistant strains show approximately equal to 14% sequence divergence from those of the penicillin-sensitive strains and the development of penicillin resistance has involved the replacement, presumably by transformation, of the original PBP2B gene by a homologous gene from an unknown source. This genetic event has occurred on at least two occasions, involving different sources, to produce the two classes of altered PBP2B genes found in penicillin-resistant strains of S. pneumoniae. There is considerable variation among the PBP2B genes of the resistant strains that may have arisen by secondary transformation events accompanied by mismatch repair subsequent to their original introductions into S. pneumoniae.

Aminoacyltransferases

Characteristics and antibiotic therapy of adult meningitis due to penicillin-resistant pneumococci.

Of 66 episodes of pneumococcal meningitis seen in Bellvitge Hospital, Barcelona, Spain (January 1981 to June 1987), 15 (23 percent) were due to penicillin-resistant pneumococci [minimal inhibitory concentrations (MICs) of 0.1 to 4 micrograms/ml]. Fifty percent of these strains were also resistant to chloramphenicol. Most were sporadic community-acquired cases. Clinical characteristics were similar in both penicillin-resistant and penicillin-sensitive cases. Those cases with MICs of greater than 1 microgram/ml did not show a response to penicillin therapy. Of nine patients treated with cefotaxime (200 to 350 mg/kg per day) with penicillin G MICs of 0.1 to 4 micrograms/ml and cefotaxime MICs of less than or equal to 0.03 to 1 microgram/ml, seven recovered, one experienced a relapse after 14 days of therapy and the infection was cured with intravenous vancomycin, and one patient died with sterile cerebrospinal fluid. Thus, adults with meningitis due to penicillin-resistant pneumococci may be adequately treated with high doses (around 300 mg/kg per day) of intravenous cefotaxime if MICs of penicillin G are less than or equal to 4 micrograms/ml. Cases with higher resistance may require another antibiotic such as vancomycin.

Adult

Risk factors and response to antibiotic therapy in adults with bacteremic pneumonia caused by penicillin-resistant pneumococci.

We retrospectively studied 24 adults with bacteremic pneumonia (25 episodes) due to penicillin-resistant pneumococci, for which the minimal inhibitory concentrations (MICs) of penicillin G were 0.12 to 8.0 micrograms per milliliter; 79 percent of the strains showed multiple antibiotic resistance. As compared with 48 control patients with bacteremic pneumonia caused by penicillin-sensitive pneumococci, the 24 patients with penicillin-resistant pneumococci had a significantly higher incidence of use of beta-lactam antibiotics during the previous three months (65 vs. 17 percent, P = 0.0008), hospitalization during the previous three months (58 vs. 21 percent, P = 0.0038), nosocomial pneumonia (37 vs. 6 percent, P = 0.0032), episodes of pneumonia during the previous year (29 vs. 4 percent, P = 0.010), and factors on initial presentation that were associated with a poor prognosis (an initially critical condition) (67 vs. 27 percent, P = 0.0030). Their overall mortality rate was significantly higher (54 vs. 25 percent, P = 0.0298). Eleven of 19 episodes of pneumonia due to organisms for which MICs were 0.12 to 2.0 micrograms per milliliter, which were treated with penicillin G (10 episodes) or another beta-lactam agent (9 episodes), resulted in recovery (2 of 10 patients in an initially critical condition recovered, as compared with all of 9 not initially in a critical condition, P = 0.0012). Two patients who had penicillin-resistant pneumococci for which MICs were 4.0 and 8.0 micrograms per milliliter did not respond to ampicillin and ticarcillin therapy, respectively. Our study suggests that pneumonia due to penicillin-resistant pneumococci may occur more often in a population with some identifiable risk factors, and may respond to intravenous high-dose penicillin therapy if MICs are less than or equal to 2 micrograms per milliliter. Cases involving higher resistance may require an alternative antibiotic.

Anti-Bacterial Agents