Javier Cobo

Outbreak of a Multiresistant Klebsiella pneumoniae Strain in an Intensive Care Unit: Antibiotic Use as Risk Factor for Colonization and Infection

An observational study was undertaken to describe a nosocomial outbreak caused by multiresistant Klebsiella pneumoniae (MRKP). Ten patients in the pediatric intensive care unit (ICU) at a hospital in Madrid were colonized by or infected with MRKP from October 1997 to April 1998. Thirty-two patients with MRKP-negative surveillance cultures who were admitted to the ICU during the outbreak period were selected as control patients. Random amplified polymorphic DNA analysis of MRKP isolates revealed patterns that were indistinguishable from each other. After identification of colonized patients by surveillance cultures and implementation of standard and contact precautions, the outbreak was controlled. An age <12 weeks (odds ratio [OR], 13.1) and previous treatment with third-generation cephalosporins and aminoglycosides (OR, 31.2) were independently associated with MRKP colonization and/or infection. Individual exposure to antibiotics, irrespective of other clinical determinants, is a risk factor for MRKP acquisition. Screening high-risk patients during outbreaks and reducing the use of third-generation cephalosporins and aminoglycosides contribute to the control of these epidemics.

High Rate of Intestinal Colonization with Extended-Spectrum-β-Lactamase-Producing Organisms in Household Contacts of Infected Community Patients

ABSTRACT Fecal carriage of extended-spectrum-β-lactamase (ESBL)-producing organisms was detected in 70% of index cases of patients (n = 40) with community-acquired infections due to ESBL producers and reached 16.7% in household contacts (n = 54). A total of 66% of ESBL-producing organisms from index cases were indistinguishable from isolates from household contacts by pulsed-field gel electrophoresis. Patients with community infections and members of their households represent a reservoir for ESBL producers, increasing dispersal of resistance in healthy people.

A Large Multicenter Study of Methicillin–Susceptible and Methicillin–Resistant Staphylococcus aureus Prosthetic Joint Infections Managed With Implant Retention

BACKGROUND Several series predicting the prognosis of staphylococcal prosthetic joint infection (PJI) managed with debridement, antibiotics, and implant retention (DAIR) have been published, but some of their conclusions are controversial. At present, little is known regarding the efficacy of the different antibiotics that are used or their ability to eliminate methicillin-resistant S. aureus (MRSA) infection. METHODS This was a retrospective, multicenter, observational study of cases of PJI by S. aureus that were managed with DAIR (2003-2010). Cases were classified as failures when infection persistence/relapse, death, need for salvage therapy, or prosthesis removal occurred. The parameters that predicted failure were analyzed with logistic and Cox regression. RESULTS Out of 345 episodes (41% men, 73 years), 81 episodes were caused by MRSA. Fifty-two were hematogenous, with poorer prognoses, and 88% were caused by methicillin-susceptible S. aureus (MSSA). Antibiotics were used for a median of 93 days, with similar use of rifampin-based combinations in MSSA- and MRSA-PJI. Failure occurred in 45% of episodes, often early after debridement. The median survival time was 1257 days. There were no overall prognostic differences between MSSA- and MRSA-PJI, but there was a higher incidence of MRSA-PJI treatment failure during the period of treatment (HR 2.34), while there was a higher incidence of MSSA-PJI treatment failure after therapy. Rifampin-based combinations exhibited an independent protective effect. Other independent predictors of outcome were polymicrobial, inflammatory, and bacteremic infections requiring more than 1 debridement, immunosuppressive therapy, and the exchange of removable components of the prosthesis. CONCLUSIONS This is the largest series of PJI by S. aureus managed with DAIR reported to date. The success rate was 55%. The use of rifampin may have contributed to homogenizing MSSA and MRSA prognoses, although the specific rifampin combinations may have had different efficacies.

Nosocomial transmission of Mycobacterium bovis resistant to 11 drugs in people with advanced HIV-1 infection

BACKGROUND Since 1990, several nosocomial outbreaks of multidrug-resistant (MDR) tuberculosis have occurred, none of which have involved Mycobacterium bovis. We describe an epidemic of nosocomial and primary MDR M bovis tuberculosis from December, 1993, to February, 1995, among HIV-1-infected patients in a district of Madrid. METHODS We undertook genetic characterisation of the M bovis strain and investigated its presence in a tuberculosis epidemic in a Madrid hospital in a case-controlled study. We assessed 19 cases diagnosed with MDR tuberculosis due to M bovis during the study period. For the control group, we randomly selected 33 patients with HIV-1 infection and isolation of a strain of M tuberculosis susceptible to isoniazid, rifampicin, or both, who were treated in Ramón y Cajal Hospital. Infection-control policies and practices were implemented. FINDINGS We detected 19 cases in HIV-1-infected patients of primary MDR tuberculosis produced by M bovis resistant to 11 antituberculosis drugs. We found phenotypic and genotypic similarities in the strains of M bovis. In the case group, the index case and two other cases had had previous contact with another hospital that had had an MDR tuberculosis outbreak. All patients died after a mean of 44 days (range 2-116), despite multidrug treatment with first-line and second-line antituberculosis drugs. The cases with M bovis MDR tuberculosis were significantly more likely than controls to have been admitted to a hospital ward at the same time as patients already infected with MDR tuberculosis during the 10 months before their diagnosis (adjusted odds ratio 94.6 [95% CI 9.4-956.3], p < 0.0001). Advanced HIV-1 immunosuppression was associated with the development of MDR tuberculosis. Implementation of control measures stopped the epidemic. INTERPRETATION An M bovis primary MDR tuberculosis epidemic that cannot be treated effectively and with high mortality has emerged in Europe and has been transmitted between hospitals.

Complex Clonal and Plasmid Epidemiology in the First Outbreak of Enterobacteriaceae Infection Involving VIM-1 Metallo-β-Lactamase in Spain: Toward Endemicity?

BACKGROUND We report the emergence and spread of metallo-beta-lactamases (MBLs) among enterobacterial isolates at Ramón y Cajal University Hospital (Madrid, Spain). METHODS AND RESULTS During the period from March 2005 through September 2006, 25 patients (52% of whom were in the intensive care unit) were infected and/or colonized with single or different MBL-producing Enterobacteriaceae isolates (Klebsiella pneumoniae, 14 patients; Enterobacter cloacae, 12 patients; Escherichia coli, 1 patient; and/or Klebsiella oxytoca, 1 patient). Clonal analysis (XbaI pulsed-field gel electrophoresis) revealed that all K. pneumoniae isolates belonged to the same clone, but 6 patterns were found among the E. cloacae isolates. Carbapenems were affected to different degrees (minimum inhibitory concentration, < or = 1 to > 8 microg/mL), as were aminoglycosides and ciprofloxacin. The bla(VIM-1) MBL gene was present in all isolates; in addition, the bla(SHV-12) extended-spectrum beta-lactamase gene was detected in K. pneumoniae and E. coli isolates. The bla(VIM-1) gene was detected within a 4.0-kb class 1 integron (bla(VIM-1)-aacA4-dfrII-aadA1-catB2) in K. pneumoniae and E. coli and in a 2.5-kb class 1 integron (bla(VIM-1)-aacA4-aadA1) in E. cloacae and K. oxytoca isolates. The bla(VIM-1) gene was transferable (filter-mating) in 14 of 14 K. pneumoniae isolates, 4 of 11 E. cloacae isolates, and 1 of 1 E. coli isolate. A 60-kb plasmid belonging to the IncI1 group was detected in the epidemic VIM-1-K. pneumoniae clone. Plasmids of 300- or 435-kb belonging to IncH12 group were found among E. cloacae isolates. CONCLUSIONS K. pneumoniae-MBL monoclonal epidemics coexisted with E. cloacae-MBL multiclonal epidemics in our hospital. The spread of the bla(VIM-1) gene among Enterobacteriaceae was driven by clonal spread associated with intergeneric plasmid transfer with different class I integron platforms. Such complex epidemiology might anticipate endemicity and should be considered for the design of containment epidemiology strategies.

Secular Trends of Candidemia in a Large Tertiary-Care Hospital From 1988 to 2000: Emergence of Candida parapsilosis

OBJECTIVE To analyze the secular trends of candidemia in a large tertiary-care hospital to determine the overall incidence, as well as the incidence by ward and by species, and to detect the occurrence of outbreaks. DESIGN Retrospective descriptive analysis. Secular trends were calculated using the Mantel-Haenszel test. SETTING A large tertiary-care referral center in Spain with a pediatric intensive care unit (ICU) to which more than 500 children with congenital cardiac disease are admitted annually. PATIENTS All patients with candidemia occurring from 1988 to 2000 were included. Cases were identified from laboratory records of blood cultures. RESULTS There were 331 episodes of candidemia. The overall incidence of nosocomial candidemia was 0.6 episode per 1,000 admissions and remained stable throughout the study period (P = .925). The species most frequently isolated was Candida albicans, but the incidence of C. parapsilosis candidemia increased (P = .035). In the pediatric ICU, the incidence of C. parapsilosis was 5.6 episodes per 1,000 admissions and it was the predominant species. Outbreaks occurred occasionally in the pediatric ICU, suggesting nosocomial transmission. CONCLUSIONS During this 13-year period, the incidence of candidemia remained stable in this hospital, but C. parapsilosis increased in frequency. Occasional outbreaks of candidemia suggested nosocomial transmission of Candida species.

Intravenous colistin sulphomethate sodium for therapy of infections due to multidrug-resistant gram-negative bacteria

OBJECTIVE To assess the efficacy and toxicity of intravenous colistin in the treatment of infections due to multidrug-resistant gram-negative bacteria. METHODS Retrospective cohort study. RESULTS Sixty patients received colistin sulphomethate sodium (mean dose, 4.4mg/kg/day; median duration, 20days). The main infections were pneumonia or tracheobronchitis (63.3%), intra-abdominal (10%), urinary tract (8.3%), and surgical site infection (6.6%), primary bacteremia (5%), catheter infection (3.3%), meningitis (1.6%), and soft-tissue infection (1.6%). The responsible bacteria were Acinetobacter spp. (50%), P. aeruginosa (23.3%), K. pneumoniae (13.3%), Enterobacter spp. (10%), E. coli (1.6%), and S. maltophilia (1.6%). Eight patients (13%) received colistin monotherapy, and 52 (87%) received combination therapy with other antibiotics such as beta-lactams (15 cases), aminoglycosides (14), beta-lactams and aminoglycosides (15), or ciprofloxacin (8). A favourable response was observed in 43 cases (71.7%). Overall mortality was 26.7%. Despite the common use of combination therapy with aminoglycosides (48%), nephrotoxicity during colistin therapy was observed in only 10.9% of patients; most of them had previous renal failure. CONCLUSION Colistin appears to be an effective and safe drug for therapy of severe infections due to multidrug-resistant gram-negative bacteria. Despite the concomitant use of aminoglycosides in a high proportion of patients, renal toxicity was an uncommon adverse event.

Candidal Meningitis in HIV-Infected Patients: Analysis of 14 Cases

Five cases of candidal meningitis in human immunodeficiency virus (HIV)-infected patients have been diagnosed in our hospital. This article describes these cases and reviews another nine previously reported in the literature. Most patients (71%) had at least one well-known predisposing factor for candidiasis. Median CD4 cell count was 135/mm3. Headache and fever, in the absence of focal neurologic signs, were the predominant clinical features. The CSF analysis revealed mild pleocytosis and hypoglycorrachia, indistinguishable from those seen in tuberculous or cryptococcal meningitis. Twelve patients (92%) received amphotericin B for a median of 51 days, in combination with flucytosine in five cases. The overall mortality among treated patients was 31%. Although the risk of relapse of candidal meningitis is unknown, maintenance antifungal therapy was given to seven patients (63%), usually with fluconazole. Candida species must be kept in mind as a cause of chronic meningitis in HIV-infected patients who have a known predisposing factor.

Clinical study of 44 cases of Staphylococcus aureus meningitis

Abstract.In order to describe the clinical features and outcome of Staphylococcus aureus meningitis, the charts of 44 cases seen at one teaching hospital during a 20-year period were retrospectively reviewed. Staphylococcus aureus was the fifth most common cause of bacterial meningitis (10.2% of cases). There were 28 (63%) cases of postoperative meningitis and 16 (37%) of spontaneous meningitis. Patients with postoperative meningitis were younger than patients with spontaneous meningitis (mean age, 40.3 vs. 59.3 years; P=0.04) and had a lower frequency of community-acquired infection (32.1% vs. 93.8%; P<0.01), severe underlying diseases (28% vs. 87%; P<0.01) and associated staphylococcal infection (35% vs. 75%; P=0.01). The clinical presentation was similar in both groups, but patients with postoperative meningitis had a lower frequency of altered mental status (39% vs. 75%; P=0.02), meningeal signs (28% vs. 62%; P=0.02), petechial rash (0% vs. 18%; P=0.04), bacteremia (7% vs. 75%; P<0.01), and septic shock (0% vs. 44%; P<0.01). Most patients were treated with cloxacillin or vancomycin, with or without rifampicin, for a mean period of 22.5 days (range, 1–100 days). Overall mortality was 27%, and the mortality rate was higher for cases of spontaneous than postoperative meningitis (50% vs. 14%; P=0.01). Mortality correlated significantly with advanced age, spontaneous meningitis, altered mental status, and the presence of severe underlying diseases, bacteremia, and septic shock.

Trends in neurological complications of endocarditis

Neurological complications (NCs) are a major cause of morbidity and mortality in patients with infectious endocarditis (IE). The frequency of these complications has been found to remain constant since the preantibiotic era despite profound epidemiological changes and therapeutic advances. We have reviewed retrospectively all the cases of IE attended at a single institution between 1985 and 2003, aiming to study the clinical characteristics of the NCs, and to analyse possible temporal trends in their frequency. Among 550 patients with IE, 71 (13%) suffered NCs. NCs presented more frequently in native (NVE) and prosthetic (PVE) valve endocarditis (17% and 20%, respectively) than in endocarditis associated with drug addiction (IDU-NVE) or pacemeker (6% and 9%, respectively). Cerebrovascular disorders were the most frequent NCs (60% of the patients had ischemic events and 21% had haemorrhages). Meningitis and cerebral abscess occurred in 16% and 3% of patients with NCs, respectively, and diffuse encephalopathy in 13%. Staphylococus aureus infection was the only factor associated with NCs, but only in NVE. During the study period there was a trend for increasing frequency of NCs in IE patients, probably associated to several factors: a decrease in IDUNVE, an increase in more aggressive nosocomial acquired NVE, and an increase in NVE caused by S. aureus. Mortality among patients with NCs (34%) was significantly higher than in IE patients without them (11%). During the study period mortality increased in patients with NVE and NCs.