[Show abstract][Hide abstract] ABSTRACT: Background. There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for
MRSA infective endocarditis and complicated bacteremia.
Methods. The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or
endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem
(1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72
hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy).
Results. The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated
bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5.
Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and
only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient
with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia
Conclusions. Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream
infections and deserves further clinical evaluation as initial therapy in these infections.
[Show abstract][Hide abstract] ABSTRACT: The present article is an update of the literature on endocarditis. A multidisciplinary group of Spanish physicians with an interest in cardiac infections selected the most important papers produced lately in the field. Two of the members of the group discussed the content of each of the selected papers, with a critical review by others members of the panel. After a review of the state of the art papers from the fields of epidemiology, new causative microorganisms (bacterial and fungal), clinical findings including those in special patients, laboratory diagnosis, prognostic factors, nosocomial endocarditis, prophylaxis, new drugs and guidelines for antibiotic treatment were discussed by the group.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Catheter-related bloodstream infection (CR-BSI) is a cause of morbidity and mortality in intensive care units, and the optimal approach for preventing these infections is not well defined. Comparison of CR-BSI rates with those provided by programs such as the National Nosocomial Infection Surveillance System (NNISS) from the USA and the Spanish National Nosocomial Infection Surveillance Study (ENVIN), enable determination of the need to implement control measures. In 2000, we found that the CR-BSI rates in UCIs of our hospital were much higher than the data reported by ENVIN. Objective: To assess the impact of implementing a protocol for proper use of intravascular catheters on CR-BSI rates in the intensive care unit (ICU) of a tertiary hospital. Methods: Prospective study of patients admitted to the ICUs of a tertiary hospital in the months of May and June, from 2000 to 2004. In 2001, a CR-BSI prevention program including aspects related to catheter insertion and maintenance in ICU patients was implemented. We calculated infection rates per 1000 days of catheter use in all the 2-month periods studied, and compared the 2000 and 2004 results by analysis of the odds ratios and confidence intervals.
[Show abstract][Hide abstract] ABSTRACT: Catheter-related bloodstream infection (CR-BSI) is a cause of morbidity and mortality in intensive care units, and the optimal approach for preventing these infections is not well defined. Comparison of CR-BSI rates with those provided by programs such as the National Nosocomial Infection Surveillance System (NNISS) from the USA and the Spanish National Nosocomial Infection Surveillance Study (ENVIN), enable determination of the need to implement control measures. In 2000, we found that the CR-BSI rates in UCIs of our hospital were much higher than the data reported by ENVIN.
To assess the impact of implementing a protocol for proper use of intravascular catheters on CR-BSI rates in the intensive care unit (ICU) of a tertiary hospital.
Prospective study of patients admitted to the ICUs of a tertiary hospital in the months of May and June, from 2000 to 2004. In 2001, a CR-BSI prevention program including aspects related to catheter insertion and maintenance in ICU patients was implemented. We calculated infection rates per 1000 days of catheter use in all the 2-month periods studied, and compared the 2000 and 2004 results by analysis of the odds ratios and confidence intervals.
A total of 923 patients were included. Mean age was 58.7 years (SD: 15.4), mean ICU stay was 11.6 days (SD: 11.4), mean SAPSII was 28.2 (SD: 15.9), and mortality was 20.5%. There was a significant reduction in CR-BSI rates from 13.3 episodes per 1000 days of catheter use in the first period to 3.21 in the last period (OR=3.53, 95% CI: 2.36-5.31).
Application of a prevention program for CR-BSI and a system for monitoring BSI rates led to a significant, sustained reduction in these infections.
[Show abstract][Hide abstract] ABSTRACT: To describe the incidence and clinical characteristics of imipenem-resistant (IR) Pseudomonas aeruginosa bacteraemia.
We performed a retrospective study including all episodes of IR P. aeruginosa bacteraemia seen from January 2003 to December 2005 in a tertiary teaching hospital.
There were 108 episodes of IR P. aeruginosa bacteraemia, which represented an incidence of 0.14 episodes per 1000 patient-days in 2003 and 0.11 episodes per 1000 patient-days in 2005. 83 of the episodes (77%) were nosocomially acquired. Most of patients had at least one underlying disease and had previously received antimicrobial treatment. The most frequent source was the urinary tract (31%), followed by unknown origin (22%). A total of 23 (21%) episodes were polymicrobial and 51 (47%) were caused by multidrug-resistant strains. The independent risk factors for mortality from IR P. aeruginosa bloodstream infection were a high-risk source of the bacteraemia (OR: 4.6; 95% CI 1.7-12.4; p=0.01), and presentation with severe sepsis (OR: 2.8; 95% CI 1-7.8; p=0.05).
Our study shows that the rates of IR P. aeruginosa bacteraemia remained stable throughout the study period. The source of bacteraemia and the clinical presentation with severe sepsis were the main determinants of the prognosis.
The Journal of infection 05/2009; 58(4):285-90. DOI:10.1016/j.jinf.2009.02.010 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and clinically important. The rise in MRSA bacteremia and endocarditis is related with the increasing use of venous catheters and other vascular procedures. Glycopeptides have been the reference drugs for treating these infections. Unfortunately their activity is not completely satisfactory, particularly against MRSA strains with MICs > 1 microg/mL. The development of new antibiotics, such as linezolid and daptomycin, and the promise of future compounds (dalvabancin, ceftobiprole and telavancin) may change the expectatives in this field.The principal aim of this consensus document was to formulate several recommendations to improve the outcome of MRSA bacteremia and endocarditis, based on the latest reported scientific evidence. This document specifically analyzes the approach for three clinical situations: venous catheter-related bacteremia, persistent bacteremia, and infective endocarditis due to MRSA.
[Show abstract][Hide abstract] ABSTRACT: El presente artículo recoge una actualización bibliográfica de patógenos bacterianos. Dado el interés científico y la importancia que tienen para la salud pública las infecciones producidas por patógenos bacterianos con nuevos mecanismos de virulencia y/o nuevos mecanismos de resistencia a los antimicrobianos, un grupo multidisciplinario de microbiólogos y clínicos españoles, con experiencia en enfermedades infecciosas, organizó una reunión en la que se revisaron los artículos más importantes en este campo, publicados en 2006.
El contenido de cada uno de los artículos seleccionados fue expuesto y discutido por uno de los miembros del grupo. Este artículo revisa algunas de las enfermedades infecciosas bacterianas que suponen hoy en día algunos de los principales retos para la salud pública e incluye las infecciones producidas por Staphylococcus aureus resistente a meticilina de adquisición comunitaria, las producidas por variantes de colonia pequeña de S. aureus, las relacionadas con estafilococos coagulasa negativa multirresistentes, la infección neumocócica, la listeriosis humana, la infección meningocócica, la tos ferina, las infecciones por Haemophilus influenzae, la diseminación de las bacterias productoras de BLEE, y las infecciones por bacilos gramnegativos no fermentadores. Tras la revisión de la situación actual, se discuten y comentan diferentes artículos relacionados con estos aspectos.
[Show abstract][Hide abstract] ABSTRACT: La sepsis grave y el shock séptico son causas frecuentes de fallecimiento en las unidades de cuidados intensivos (UCI). La incidencia de sepsis se ha incrementado durante los 2 últimos decenios y se considera que lo va a seguir haciendo durante los próximos años. A pesar de que actualmente poseemos mucha más información acerca de las complejas alteraciones fisiopatológicas que tienen lugar en la sepsis grave y en el shock séptico, los pacientes con sepsis siguen presentando un elevado riesgo de muerte. Sin embargo, durante los últimos años la introducción de nuevas estrategias terapéuticas ha mejorado significativamente el pronóstico de estos pacientes. En este artículo se revisan nueve estudios de gran envergadura publicados en 2004 y 2005: en dos de ellos se abordan las tasas de incidencia, la distribución de los patógenos y las tendencias en la resistencia frente a los antibióticos en los pacientes con sepsis atendidos en la UCI; en otros dos artículos se exponen diversos aspectos seleccionados del tratamiento antibiótico, la utilidad del tratamiento de combinación en los cuadros de sepsis que presentan los pacientes inmunocompetentes y el impacto del tratamiento empírico en los cuadros de sepsis causados por Pseudomonas aeruginosa; en otras dos publicaciones se consideran la utilidad de la evaluación del riesgo en el tratamiento de la sepsis y la importancia de una evaluación clínica dinámica en los pacientes con infección y en situación clínica crítica. En los tres estudios restantes se analiza el tratamiento complementario en la sepsis grave: el efecto de un protocolo de control intensivo de la glucemia sobre la evolución de los pacientes en situación clínica crítica; la evaluación de la insuficiencia suprarrenal relativa y de la variabilidad de las concentraciones plasmáticas de cortisol durante un período de 24 horas, y el uso de drotrecogina alfa (activada) en los adultos con sepsis grave y riesgo bajo de muerte.
[Show abstract][Hide abstract] ABSTRACT: To investigate an increase in the number of Salmonella enteritidis isolates detected in a large hospital to ascertain whether it was due to a nosocomial source, to identify the mechanisms of transmission, and to institute effective control measures to prevent future episodes.
Observational study, survey of all microbiological samples positive for S. enteritidis detected in the hospital, outbreak investigation, and review of the literature.
A tertiary-care teaching hospital for adults in Barcelona, Spain.
During a 7-month period from May to November 1998, we identified 22 inpatients with S. enteritidis infection for whom nosocomial acquisition was strongly suspected. The attack rate was 0.138 per 1,000 patient-days. All affected patients were immunosuppressed and overall mortality was 41% (9 of 22). A sample of a meal cooked in the kitchen was culture positive for S. enteritidis. All isolates shared the same antibiotic susceptibility pattern and all except one shared the same pulsed-field gel electrophoresis (PFGE) pattern, but PFGE could not differentiate between outbreak-related and control strains. After compliance with kitchen hygiene procedures was emphasized and cleansing was intensified, no more cases were detected.
Apparently, sporadic cases of S. enteritidis may be part of an outbreak with a low attack rate. A small but persistent inoculum affecting only individuals with special predisposition for Salmonella infection might account for this. Suspicion should be raised in hospitals and institutions with a highly susceptible population.
Infection Control and Hospital Epidemiology 02/2004; 25(1):10-5. DOI:10.1086/502284 · 4.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An outbreak due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) was detected from May 1993 to June 1995. A total of 145 patients, particularly patients in intensive care units (ICUs) (107 patients [72%]), were colonized or infected. Infection developed in 92 (63%) patients, and primary bacteremia caused by ESBL-KP was the most frequent infection (40 of 92 patients [43%]). A single clone of ESBL-KP was identified by pulsed-field gel electrophoresis analysis throughout the whole period, and no molecular epidemiological relationship could be found between the epidemic strain and non-ESBL-KP isolates. To determine risk factors for ESBL-KP infection weekly rectal swabs were obtained in three serial incidence surveys (470 patients); the probabilities of carriage of ESBL-KP in the digestive tract were 33% (October and November 1993), 40% (May and June 1994), and 0% (October and November 1995) at 10 days of ICU admission. A logistic regression model identified prior carriage of ESBL-KP in the digestive tract (odds ratio, 3.4; 95% confidence interval 1.1 to 10.4) as an independent variable associated with ESBL-KP infection. A statistically significant correlation was observed between the restricted use of oxyimino-beta-lactams (189 defined daily doses [DDD]/ 1,000 patient-days to 24 DDD/1,000 patient-days) and the trends of ESBL-KP infection (r = 0.7; P = 0.03).
Antimicrobial Agents and Chemotherapy 02/1998; 42(1):53-8. · 4.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Fifty evaluable patients (34 men and 16 women; mean age, 47 years) with severe infections were given intravenous ciprofloxacin (200 mg every 12 hours) for a mean of 14 days. Therapy was continued with oral ciprofloxacin 500 to 750 mg every 12 hours in 34 cases for a mean of 57 days. The sources of the infections were bone and joint (26 patients), respiratory tract (10 patients), urinary tract (four patients), soft tissue (four patients), abdominal (three patients), bacteremia of unknown origin (two patients), and right-sided endocarditis (one patient). Fifteen patients (30 percent) were bacteremic. Causative organisms included Pseudomonas aeruginosa (32 patients), other gram-negative bacilli (18 patients), and gram-positive cocci (nine patients). Minimal inhibitory concentrations ranged between 0.03 and 1 microgram/ml. Mean peak serum concentrations were 1.58 micrograms/ml (intravenous) and 2 micrograms/ml (oral); mean trough serum concentrations were 0.23 micrograms/ml (intravenous) and 0.32 micrograms/ml (oral). Serum bactericidal activity values achieved after intravenous and oral therapy were similar. Response to therapy was evaluated separately in patients with or without osteomyelitis. In 30 patients with infections other than osteomyelitis, clinical cure was achieved in 27 (90 percent), and therapy failure occurred in three patients. In the 20 remaining patients with osteomyelitis, 15 (75 percent) had a satisfactory response, with apparent cure after a mean follow-up of 11 months, whereas five had therapeutical failure (P. aeruginosa became resistant in four of them). Overall, no major adverse effects were encountered. Superinfection by a resistant P. aeruginosa was observed in three patients. Intravenous ciprofloxacin is an effective and safe agent for the therapy of severe infections caused by susceptible organisms.
The American Journal of Medicine 12/1989; 87(5A):221S-224S. DOI:10.1016/0002-9343(89)90063-6 · 5.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
The American Journal of Medicine 06/1988; 84(5):839-46. DOI:10.1016/0002-9343(88)90061-7 · 5.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
New England Journal of Medicine 08/1987; 317(1):18-22. DOI:10.1056/NEJM198707023170104 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the efficacy of aztreonam in the treatment of spontaneous bacterial peritonitis in patients with hepatic cirrhosis, 14 patients (7 males, 7 females) with 16 Gram-negative infective episodes (12 Escherichia coli and 4 Klebsiella pneumoniae) were treated with aztreonam infusions at doses of 1 gm per 8 hr for a planned 14-day period. Ages ranged from 40 to 75 years with a mean of 57 ± 10 years.
All organisms were highly susceptible to aztreonam (minimal inhibitory concentration ⩽ 0.06 to 0.12 μg per ml). Serum antibiotic levels were 61.9 ± 25.5 μg per ml (peak) and 27 ± 18.5 μg per ml (trough). Ascitic fluid antibiotic levels were 33.6 ± 22.5 μg per ml (peak) and 32.7 ± 16.8 μg per ml (trough).
Although the symptoms of infection were controlled within 3 days and ascitic fluid cultures became negative after 48 hr, 10 patients (62.5%) died, with hepatorenal syndrome and digestive tract hemorrhage as the principal causes of death. Three patients developed streptococcal superinfections during treatment; Streptococcus faecalis peritonitis in one case and spontaneous bacteremia due to Streptococcus equinus and Streptococcus mutans in the other two.
Aztreonam was well tolerated and clinically and bacteriologically efficacious in controlling the infection. Serum and ascitic fluid levels were considerably higher than the minimal inhibitory concentration for the causative organisms, suggesting that lower doses may achieve suitable therapeutic levels.
A negative aspect of the antibiotic therapy was the superinfections. The high mortality rate was attributable to the generally poor underlying condition of the patients.