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J Gavaldà

Publications and source records attributed to J Gavaldà.

At least 19 recordsLinked to original sources

Donor-to-host transmission of bacterial and fungal infections in lung transplantation.

The purpose of this study was to evaluate the incidence and etiology of bacterial and fungal infection or contamination in lung allograft donors and to assess donor-to-host transmission of these infections. Recipients who survived more than 24 h and their respective donors were evaluated. The overall incidence of donor infection was 52% (103 out of 197 donors). Types of donor infection included isolated contamination of preservation fluids (n = 30, 29.1%), graft colonization (n = 65, 63.1%) and bacteremia (n = 8, 7.8%). Donor-to-host transmission of bacterial or fungal infection occurred in 15 lung allograft recipients, 7.6% of lung transplants performed. Among these cases, 2 were due to donor bacteremia and 13 to colonization of the graft. Twenty-five percent of donors with bacteremia and 14.1% of colonized grafts were responsible for transmitting infection. Excluding the five cases without an effective prophylactic regimen, prophylaxis failure occurred in 11 out of 197 procedures (5.58%). Donor-to-host transmission of infection is a frequent event after lung transplantation. Fatal consequences can be avoided with an appropriate prophylactic antibiotic regimen that must be modified according to the microorganisms isolated from cultures of samples obtained from donors, grafts, preservation fluids and recipients.

Bacteria↗

Preemptive therapy with intravenous ganciclovir for the prevention of cytomegalovirus disease in lung transplant recipients.

The most effective strategy for the prevention of cytomegalovirus (CMV) disease in lung transplantation has not been conclusively established. The aim of this study was to determine the efficacy of preemptive ganciclovir therapy for this purpose. Twenty-five consecutive adult patients positive for CMV before transplantation and surviving more than 30 days after the procedure were studied. Mean follow-up was 732.2 days (range, 210-1125). All patients received intravenous (IV) ganciclovir prophylaxis for the first 21 days and subsequently underwent frequent CMV antigenemia monitoring: weekly for the first 3 months, every 15 days between 3 and 6 months, and monthly thereafter. IV ganciclovir was given when antigenemia results were greater than 10 infected cells per 100,000 polymorphonuclears. The study group was compared with a historical group of 30 consecutive patients who had received IV ganciclovir prophylaxis and continued on oral ganciclovir up to day 120 posttransplantation. Eighteen of the 25 patients (72.0%) presented episodes of CMV infection. Six of the 25 patients (24.0%) had CMV disease, including 3 viral syndromes and 3 cases of pneumonitis. Four patients debuted with CMV disease, 1 of them with pneumonitis. CMV resistance to ganciclovir was observed in 2 patients. The incidence of infection was higher than in the historical group (72.0% vs 46.7%; P < .05), but there were no significant differences in the incidence of CMV disease (24.0% vs 40.0%; P = not significant [NS]). Mean time before onset of the first episode of disease was lower in the preemptive therapy group than in the comparison patients (82.8 days; range, 42-240 vs 175 days; range, 90-243; P < .05). In conclusion, preemptive therapy for CMV disease is as effective a prevention strategy as oral ganciclovir prophylaxis. However, the early appearance of CMV disease with preemptive therapy can make this approach inadvisable.

Administration, Oral↗

Contamination of the nebulization systems used in the prophylaxis with amphotericin B nebulized in lung transplantation.

The contamination of nebulizer may be the origin of respiratory infections. The aim of this study was to determine the incidence of contamination in nebulizers used to nebulize amphotericin B in lung transplant (LT) patients and the relationship with bacterial isolation in sputum culture. A prospective, cross-sectional study was conducted with 41 LT patients who were administered amphotericin B with a jet nebulizer. Samples were taken from the nebulizers (prior to nebulization). Sputum culture was carried out and patients were asked whether or not they followed a cleaning and disinfection protocol (washing and brushing with soap and water followed by subsequent disinfection with the Milton method after each nebulization). Contamination was defined as such when potentially pathogenic bacteria were isolated in the nebulizer. Seventeen of the 41 nebulizers (41.4%) were contaminated. In 7 of the 17 cases (41.1%) contamination was polymicrobial. The most common microorganism was Pseudomonas aeruginosa. Fourteen of the 41 patients (34.1%) presented positive sputum cultures, most common was P aeruginosa. In 10 patients (24.3%) pathogenic bacteria was isolated both in the nebulizer and in the sputum. In four of these patients (9.7%) the species was the same. The cleaning and disinfection protocol was carried out by 16 of the 41 patients (39.0%). In 2 of the 16 patients (12.5%) who were following the protocol the nebulizer was contaminated, compared to 15 of 25 patients (60.0%) whose nebulizer was not contaminated (P < .05). Two of the 16 patients (12.%) who were following the protocol presented positive sputum culture compared to 12 of 25 (48.0%) who did not (P < .05). In conclusion, the contamination of the nebulizing systems is frequent when no strict cleaning and disinfection protocol is followed. Patients who did not follow the protocol presented a greater isolation of pathogenic bacteria in the sputum.

Amphotericin B↗

Efficacy of high loading doses of liposomal amphotericin B in the treatment of experimental invasive pulmonary aspergillosis.

This study aimed to investigate whether initial treatment of experimental pulmonary aspergillosis with high loading doses can be used as an alternative to standard therapeutic regimens. Steroid-immunosuppressed rats, infected intratracheally with Aspergillus fumigatus, received either amphotericin B deoxycholate (d-AmB) 1 mg/kg/day, liposomal amphotericin B (L-AmB) 5 mg/kg/day, or underwent a 3-day course of L-AmB 10 mg/kg, or 10 mg/kg for the first 3 or 4 days of treatment, followed by 3 mg/kg until the end of treatment. Therapy started 24 h after fungal challenge and lasted for 7 days. Compared to controls, survival was improved significantly in animals receiving any L-AmB regimen (p <or= 0.003), but not d-AmB. Compared with d-AmB, L-AmB at initial doses of 10 mg/kg followed by 3 mg/kg/day was consistently more effective, but only when measured in terms of survival, lung weight and glucosamine levels, and not log CFU. Despite the absence of significant differences between any of the L-AmB regimens, a trend towards better response rates with the higher loading dose was observed.

Amphotericin B↗

Management of catheter-related Staphylococcus aureus bacteremia: when may sonographic study be unnecessary?

This study reviews the outcome of patients with uncomplicated catheter-related Staphylococcus aureus bacteremia diagnosed in our hospital from January 1997 to December 1999 and treated with short-course antibiotic therapy. Our aim was to assess the effectiveness of this regimen for minimizing complications (relapses, endocarditis and metastatic foci). A total of 213 episodes of bacteremia were registered and 167 (78.4%) were nosocomial. Among these, 87 (52.1%) were catheter-related Staphylococcus aureus bacteremia and 20 were primary nosocomial bacteremia. Endocarditis was diagnosed during the acute episode in 7/107 of these patients (2 by persistent fever after catheter removal and 5 by metastatic foci; 3 of them also had cardiac risk factors) and confirmed with transesophageal echocardiography. Among the 84/87 catheter-related Staphylococcus aureus bacteremia and 16/20 primary nosocomial bacteremia patients who did not develop endocarditis, 31 patients died during the acute episode (16 due to sepsis despite initiation of antibiotic treatment and 15 due to the underlying disease) and five had osteoarticular foci. The remaining 64 episodes were considered to be uncomplicated bacteremia (no cardiac risk factors, persistent fever, metastatic foci, or clinical signs of endocarditis) and were treated with 10-14 days of high-dose antistaphylococcal antibiotics. Echocardiography was not mandatory in these patients. Of the 64 uncomplicated episodes, 62 were followed for at least 3 months and none relapsed or developed endocarditis. Even though some of the patients might have had subclinical endocarditis, short-course therapy with high doses of antistaphylococcal antibiotics was effective for treating uncomplicated catheter-related Staphylococcus aureus bacteremia. Transesophageal echocardiography may not be necessary in these cases.

Anti-Bacterial Agents↗

Blood cyclosporine C0 and C2 concentrations and cytomegalovirus infections following lung transplantation.

The aim of this study was to determine whether cyclosporine levels predose (C0) and at two hours postdose (C2) were higher among patients presenting with cytomegalovirus (CMV) infection or disease. Between days 40 and 365 posttransplantation serial C0 and C2 levels were measured in 15 lung transplant recipients. Nine developed 13 episodes of CMV infection or disease. Both C0 and C2 levels were higher during CMV infection or disease episodes. Eleven of the 13 CMV episodes (84%) displayed C0 >220 ng/mL and none had C0 <200 ng/mL. For C2, 11 of 13 CMV episodes (84%) showed C2 >1200 ng/mL and none had C2 <1000 ng/mL. Among determinations that did not coincide with a CMV episode, 7 of 21 (33%) showed C0 >220 and 9 of 21 (42%) showed C2 >1200, respectively (P<.05). In conclusion, cyclosporine blood levels are higher among patients presenting with CMV infection or disease.

Adult↗

Lack of antimicrobial activity of sodium heparin for treating experimental catheter-related infection due to Staphylococcus aureus using the antibiotic-lock technique.

OBJECTIVE: To elucidate the potential antimicrobial activity of sodium heparin in the treatment of catheter-infection using the antibiotic-lock technique. METHODS: We performed in vitro studies of the antibiotic susceptibility, stability and synergy of sodium heparin, vancomycin and ciprofloxacin. Efficacy studies were performed in a new animal model of Staphylococcus aureus catheter-related infection in which infection was produced via the endoluminal route. White New Zealand rabbits were surgically implanted with a sylastic catheter into the inferior cava vein. Immediately afterwards, infection was induced by filling and locking the catheters with 0.7 mL of broth culture containing 108 colony-forming units of S. aureus. Eighteen hours later the antibiotic-lock technique was started. Treatment groups were: control without treatment, sodium heparin at 2500 IU/mL, vancomycin at 2500 mg/L, ciprofloxacin at 1000 mg/L, vancomycin plus heparin and ciprofloxacin plus heparin. RESULTS: Sodium heparin showed an MIC90 higher than 6000 UI/mL against S. aureus causing catheter infection. Studies of antimicrobial synergy by the time-kill method between vancomycin and ciprofloxacin at MIC with sodium heparin at 2500 IU/mL showed no interactions. Vancomycin (2000 microg/mL) and ciprofloxacin (1000 microg/mL) in a solution containing sodium heparin (2500 IU/mL) were stable at 37 degrees C for a 72-h period. Two sets of in vivo experiments were carried out using differents strains of S. aureus. In both cases, sodium heparin showed no therapeutic efficacy when compared to control group and did not increase the antibiotic efficacy when used in combination with vancomycin or ciprofloxacin. CONCLUSION: Sodium heparin lacked antibacterial activity against S. aureus causing catheter-related infections.

Animals↗

Efficacy of teicoplanin-gentamicin given once a day on the basis of pharmacokinetics in humans for treatment of enterococcal experimental endocarditis.

With the aim of investigating home therapy for enterococcal endocarditis, we compared the efficacy of teicoplanin combined with gentamicin given once a day or in three daily doses (t.i.d.) with the standard treatment, ampicillin plus gentamicin administered t.i.d., for treating experimental enterococcal endocarditis. The antibiotics were administered by using "human-like pharmacokinetics" (H-L), i.e, pharmacokinetics like those in humans, that simulated the profiles of these drugs in human serum. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of Enterococcus faecalis EF91 (MICs and MBCs of ampicillin, gentamicin, and teicoplanin, 0.5 and 32, 16 and 32, and 0.5 and 1 microg/ml, respectively) and were treated for 3 days with ampicillin H-L at 2 g every 4 h plus gentamicin H-L at 1 mg/kg every 8 h, or teicoplanin H-L at 10 mg/kg every 24 h, alone or combined with gentamicin, administered at dose of H-L at 1 mg/kg every 8 h or H-L at 4.5 mg/kg every 24 h. The results of therapy for experimental endocarditis due to EF91 showed that teicoplanin alone was as effective as ampicillin alone in reducing the bacterial load (P > 0.05). The combination of ampicillin or teicoplanin with gentamicin was more effective than the administration of both drugs alone in reducing the log(10)CFU/gram of aortic vegetation (P < 0.01 and P < 0.05, respectively). Teicoplanin plus gentamicin H-L at 4.5 mg/kg, both administered every 24 h, showed an efficacy equal to the "gold standard," ampicillin plus gentamicin H-L at 1 mg/kg t.i.d. (P > 0.05). Increasing the interval of administration of gentamicin to a single daily dose combined with teicoplanin resulted in a reduction of bacteria in the vegetations equivalent to that achieved with the recommended regimen of ampicillin plus thrice-daily gentamicin in the treatment of experimental endocarditis due to E. faecalis. Teicoplanin plus gentamicin, both administered once a day, may be useful home therapy for selected cases of enterococcal endocarditis.

Animals↗

Efficacy of ampicillin plus ceftriaxone in treatment of experimental endocarditis due to Enterococcus faecalis strains highly resistant to aminoglycosides.

The purpose of this work was to evaluate the in vitro possibilities of ampicillin-ceftriaxone combinations for 10 Enterococcus faecalis strains with high-level resistance to aminoglycosides (HLRAg) and to assess the efficacy of ampicillin plus ceftriaxone, both administered with humanlike pharmacokinetics, for the treatment of experimental endocarditis due to HLRAg E. faecalis. A reduction of 1 to 4 dilutions in MICs of ampicillin was obtained when ampicillin was combined with a fixed subinhibitory ceftriaxone concentration of 4 micrograms/ml. This potentiating effect was also observed by the double disk method with all 10 strains. Time-kill studies performed with 1 and 2 micrograms of ampicillin alone per ml or in combination with 5, 10, 20, 40, and 60 micrograms of ceftriaxone per ml showed a > or = 2 log10 reduction in CFU per milliliter with respect to ampicillin alone and to the initial inoculum for all 10 E. faecalis strains studied. This effect was obtained for seven strains with the combination of 2 micrograms of ampicillin per ml plus 10 micrograms of ceftriaxone per ml and for six strains with 5 micrograms of ceftriaxone per ml. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of E. faecalis V48 or 10(5) CFU of E. faecalis V45 and were treated for 3 days with humanlike pharmacokinetics of 2 g of ampicillin every 4 h, alone or combined with 2 g of ceftriaxone every 12 h. The levels in serum and the pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin or ceftriaxone in rabbits were similar to those found in humans treated with 2 g of ampicillin or ceftriaxone intravenously. Results of the therapy for experimental endocarditis caused by E. faecalis V48 or V45 showed that the residual bacterial titers in aortic valve vegetations were significantly lower in the animals treated with the combinations of ampicillin plus ceftriaxone than in those treated with ampicillin alone (P < 0.001). The combination of ampicillin and ceftriaxone showed in vitro and in vivo synergism against HLRAg E. faecalis.

Algorithms↗

Response to acyclovir in two cases of herpes zoster leukoencephalitis and review of the literature.

Herpes zoster leukoencephalitis is a rare complication of varicella-zoster virus infection. Associated with high mortality, the majority of cases have been discovered postmortem; today, however, magnetic resonance imaging is being used successfully as an aid in the diagnosis of this disease. The first two reported cases of HIV-infected patients with herpes zoster leukoencephalitis who recovered clinically and showed complete resolution of the magnetic resonance demyelination images after acyclovir treatment are described. In addition, the cases of herpes zoster leukoencephalitis reported in the literature to date are reviewed.

AIDS-Related Opportunistic Infections↗

Cytomegalovirus disease as a risk factor for graft loss and death after orthotopic liver transplantation.

To determine whether cytomegalovirus (CMV) disease is an independent risk factor for graft loss and death after orthotopic liver transplantation, we performed a 3-year follow-up study of 143 consecutive liver transplant recipients and six patients who underwent retransplantation. Thirty-seven patients (25%) had had CMV disease and were alive after treatment. Fifty-two deaths and eight graft losses occurred. The cumulative incidence of graft failure at 1 and 3 years of follow-up were 40% and 63%, respectively, for patients with CMV disease, compared with 22% and 33%, respectively, for those without CMV disease (P < .05, logrank test). Cumulative probabilities of survival for patients with and without CMV disease were 64% and 82%, respectively, at 1 year and 46% and 69%, respectively, after 3 years (P < .05, logrank test). Multivariate analysis with use of a time-dependent Cox model showed that previous CMV disease was an independent risk factor for graft loss at 1 and 3 years of follow-up (P = .04 and P = .007) and for patient survival (P = .04 and P = .01). Our results indicate that CMV disease is a significant independent risk factor for graft loss and patient survival after liver transplantation.

Adolescent↗

Two grams daily of oral acyclovir reduces the incidence of cytomegalovirus disease in CMV-seropositive liver transplant recipients.

Our objective in this study was to determine the efficacy of 2 grams a day of oral acyclovir administered for 16 weeks after transplantation for the prevention of cytomegalovirus (CMV) infection and disease in CMV-seropositive liver transplant recipients. Seventy-three adult liver transplant recipients, seropositive for CMV, were randomized to receive either 2 grams a day of oral acyclovir for 16 weeks after transplantation or no prophylaxis. The incidence of CMV disease was significantly lower in the acyclovir group (5%) than in the control group (27%; P < 0.05). By log-rank analysis, the differences in the probability of presenting CMV disease over the first 16 weeks and over the 1st year were also significant (P < 0.05). We conclude that 2 grams a day of oral acyclovir provides effective prophylaxis against CMV disease in CMV-seropositive liver transplant recipients.

Acyclovir↗

Treatment of experimental pneumonia due to penicillin-resistant Streptococcus pneumoniae in immunocompetent rats.

A model of pneumonia due to Streptococcus pneumoniae resistant to penicillin was developed in immunocompetent Wistar rats and was used to evaluate the efficacies of different doses of penicillin, cefotaxime, cefpirome, and vancomycin. Adult Wistar rats were challenged by intratracheal inoculation with 3 x 10(9) CFU of one strain of S. pneumoniae resistant to penicillin (MICs of penicillin, cefotaxime, cefpirome, and vancomycin, 2, 1, 0.5, and 0.5 microg/ml, respectively) suspended in brain heart broth supplemented with 0.7% agar. The rats experienced a fatal pneumonia, dying within 5 days and with peak mortality (70 to 80%) occurring 48 to 72 h after infection, and the bacterial counts in the lungs persisted from 8.87 +/- 0.3 log10 CFU/g of lung at 24 h of the infection to 9.1 +/- 0.3 log10 CFU/g at 72 h. Four hours after infection the animals were randomized into the following treatment groups: (i) control without treatment, (ii) penicillin G at 100,000 IU/kg of body weight every 2 h, (iii) penicillin G at 250,000 IU/kg every 2 h, (iv) cefotaxime at 100 mg/kg every 2 h, (v) cefpirome at 200 mg/kg every 2 h, and (vi) vancomycin at 50 mg/kg every 8 h. Two different protocols were used for the therapeutic efficacy studies: four doses of beta-lactams and one dose of vancomycin or eight doses of beta-lactams and two doses of vancomycin. Results of the therapy for experimental pneumonia caused by penicillin-resistant S. pneumoniae showed that initially, all the antimicrobial agents tested had similar efficacies, but when we prolonged the treatment, higher doses of penicillin, cefotaxime, and cefpirome were more effective than penicillin at lower doses in decreasing the residual bacterial titers in the lungs. Also, when we extended the treatment, vancomycin was more efficacious than penicillin at lower doses but was less efficacious than higher doses of penicillin or cefpirome. The model that we have developed is simple and amenable for inducing pneumonia in immunocompetent rats and could be used to explore the pathophysiology and to evaluate optimal therapy of this infection in the immunocompetent host.

Animals↗

Rhodococcus equi pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature.

Rhodococcus equi is a cause of lung infection in immunosuppressed hosts. Since the start of the HIV epidemic, 76 cases of R. equi lung infection (MEDLINE 1985-96) affecting this population have been described. We report 2 additional cases and review the clinical data, radiological findings, treatment and outcome of these 78 patients. The mean age of these patients was 33 y; 69 were male. 71 met the criteria for AIDS (CDC 1993). Fever and cough were the presenting complaints in the majority of patients (84.3%). A single cavitary lung lesion in the upper lobes was the most common radiological finding (57.7%), although multiple cavitations, alveolar infiltrates and pleural effusion were also found. Treatment usually was based on synergistic antibiotic combinations for a long period of time determined on an individual basis. Surgery was performed only in 11 patients. Death attributable directly to R. equi infection is low (15.4%), however only half of the patients (53.8%) were completely cured. We conclude that R. equi infection should be strongly considered in any HIV patient who presents with cavitary lesions in the lung, especially if mycobacteria are not identified. Treatment must be based on synergistic antibiotic combinations, and surgery relegated to cases of chronic single cavitary lesions not responding to antibiotics.

Acquired Immunodeficiency Syndrome↗

Nontuberculous mycobacterial meningitis: report of two cases and review.

Nontuberculous mycobacterial meningitis (NTMM) is still a rare disease despite the increase in the number of cases of disseminated mycobacterial infection related to the AIDS epidemic. Moreover, there are doubts as to the clinical relevance of the isolation of mycobacteria other than Mycobacterium tuberculosis from cerebrospinal fluid. After analyzing the clinical and pathological data, we classified the cases of NTMM into three groups: definitive (28 cases), probable (19), and doubtful (5). We found that Mycobacterium avium is the most commonly isolated species (60% of cases). M. avium meningitis presents as a disseminated disease, is usually related to serious underlying conditions (mainly immunosuppression), and is associated with a death rate that approaches 70%. Mycobacterium fortuitum meningitis is associated with previous neurosurgery or back trauma; the prognosis for this infection is better when the concomitant abscesses are drained. The clinical characteristics of Mycobacterium kansasii meningitis are similar to those of M. tuberculosis meningitis, but the mortality related to M. kansasii meningitis is high despite appropriate antibiotic treatment. Herein, we present two cases of NTMM that occurred at our center, and we review 50 additional cases reported in the English-language literature.

AIDS-Related Opportunistic Infections↗

Treatment of experimental endocarditis due to Enterococcus faecalis using once-daily dosing regimen of gentamicin plus simulated profiles of ampicillin in human serum.

We compared the efficacy of ampicillin, both alone and in combination with gentamicin given once a day (q.d.) or three times a day (t.i.d.), in the treatment of experimental enterococcal endocarditis. Ampicillin was administered by using humanlike pharmacokinetics that simulated the profiles of this drug in human serum. An open one-compartment mathematical model developed in this study was used to estimate the decreasing doses administered with a computer-controlled infusion pump that simulated in rabbits the human serum pharmacokinetics after intravenous administration of 2 g of ampicillin every 4 h. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of Enterococcus faecalis J4 (MICs and MBCs of ampicillin and gentamicin, 2 and 128 and 16 and 64 micrograms/ml, respectively) and were treated for 3 days with ampicillin alone or in combination with gentamicin at 2 mg/kg of body weight subcutaneously t.i.d. or at 6 mg/kg subcutaneously q.d. The serum ampicillin levels and pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin in rabbits were similar to those found in humans treated with 2 g of ampicillin intravenously. The results of therapy for experimental endocarditis caused by E. faecalis J4 showed that the residual bacterial concentration in aortic valve vegetation was significantly lower in the animals treated with combinations of ampicillin plus gentamicin given q.d. or t.i.d. than in those treated with ampicillin alone (P < 0.01). The dosing interval of gentamicin did not significantly affect (q.d. versus t.i.d.; P = 0.673) the therapeutic efficacy of the combination of ampicillin plus gentamicin.

Ampicillin↗