Natividad Benito

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.

Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study

BackgroundData regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels.MethodsA prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.ResultsOne hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT.ConclusionsWhen using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.

Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy

Recent expert reviews recommend a conservative surgical strategy - debridement and irrigation, antibiotics and implant retention (DAIR) - for most early post-surgical prosthetic joint infections (PJI). However, differences exist in published series regarding success rates with DAIR, and the size of most series is small. In this prospective multicenter cohort study of early PJI managed by DAIR, factors associated with failure of the DAIR were analyzed. Out of 139 early PJI, 117 cases managed with DAIR were studied For 67 patients (57.3%), infection was cured and the implant was salvaged with definite antimicrobial therapy. In 35 (29.9%) DAIR failed and removal of the prosthesis was necessary during follow-up. Finally, 15 patients (12.8%) needed chronic suppressive antimicrobial therapy due to suspected or confirmed persistent infection. Infections due to methicillin-resistant S. aureus (72.7% failed; p 0.05) and those treated at one of the hospitals (80.0% failed; p <0.05) had worse outcomes, but only this last variable was associated with treatment failure following multivariate analysis. Seventy-four per cent of patients who were successfully treated by DAIR and only 32.7% of the failures were able to walk without help or with one stick at the last follow-up visit (p <0.05). In conclusion, a substantial proportion of patients with an early PJI may be successfully treated with DAIR and definite antimicrobial therapy. In more than half of these, the infection can be cured. Since identification of factors associated with failure of DAIR is not simple, we recommend offering DAIR to most patients with early PJI.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

ABSTRACT Ceftazidime-avibactam (CAZ-AVI) is a recently approved β-lactam–β-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fishers exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro. Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

The spectrum of acute bacterial meningitis in elderly patients

BackgroundWe conducted a prospective, observational study in Barcelona to determine the epidemiology, clinical features, and outcome of elderly patients with acute bacterial meningitis (ABM) compared with younger adults.MethodsDuring 1982–2010, all patients with ABM were prospectively evaluated. There were two groups: I (15–64 years) and II (≥ 65 years). All patients underwent clinical examination on admission and at discharge following a predefined protocol.ResultsWe evaluated 635 episodes of ABM. The incidence was 4.03/100,000 (Group I) and 7.40 /100,000 inhabitants/year (Group II) (RR = 1.84; 95%CI: 1.56–2.17, P < 0.0001). Elderly patients had co-morbid conditions more frequently (P < 0.0001) and more frequently lacked fever (P = 0.0625), neck stiffness (P < 0.0001) and skin rash (P < 0.0001), but had an altered level of consciousness more often (P < 0.0001). The interval admission-start of antibiotic therapy was longer for elderly patients (P < 0.0001). Meningococcal meningitis was less frequent in elderly patients (P < 0.0001), whereas listerial (P = 0.0196), gram-negative bacillary (P = 0.0065), and meningitis of unknown origin (P = 0.0076) were more frequent. Elderly patients had a higher number of neurologic (P = 0.0009) and extra-neurologic complications (P < 0.0001). The overall mortality ratio was higher in elderly patients (P < 0.0001).ConclusionsElderly people are at higher risk of having ABM than younger adults. ABM in the elderly presents with co-morbid conditions, is clinically subtler, has a longer interval admission-antibiotic therapy, and has non-meningococcal etiology. It is associated with an earlier and higher mortality rate than in younger patients.

Etiology of surgical site infections after primary total joint arthroplasties

We sought to characterize the causative pathogens of surgical site infections (SSIs) following primary total joint arthroplasties and to evaluate trends in the microbial etiology. We analyzed the etiology of SSIs following 2,632 total hip arthroplasty and knee arthroplasty procedures performed at our institution from 2004 through 2010. We calculated the annual proportion of SSIs accounted for each of the most common organisms and evaluated trends using the χ2 test for trend. SSIs were identified in 111 procedures (4.2%). The annual incidence of SSIs did not change significantly during the study period. Staphylococci were the most common cause of infection (59.6%) and most of infections were monomicrobial (82.8%). From 2004 to 2010, the annual proportion of infections due to gram‐negative bacilli (GNB) increased from 21.4% to 66.7% (p = 0.085 for trend). This increase was accompanied by a decline in the proportion of SSIs from coagulase‐negative staphylococci (p = 0.003). Additionally, we found an increase in the percentage of polymicrobial infections (from 7.1% in 2004 to 41.7% in 2010, p = 0.014). Multivariate analysis corroborated these trends. Our study reports an emergence of GNB as a cause of SSIs after primary total joint arthroplaties and an increase of polymicrobial infections.

The changing pattern of bacterial meningitis in adult patients at a large tertiary university hospital in Barcelona, Spain (1982–2010)

BACKGROUND We conducted a prospective, observational study in Barcelona (Spain) to determine changes in the spectrum of adult patients with bacterial meningitis (BM) over a 29-year period. METHODS The observation was divided into two periods: 1982-1995 (I) and 1996-2010 (II). All patients underwent clinical examination on admission and at discharge following a predefined protocol. RESULTS We evaluated 635 episodes of BM. The most frequent etiologic agents were Neisseria meningitidis and Streptococcus pneumoniae in periods I and II, respectively. Patients in period II were older (Median: 47.5 [95%CI: 23.0-64.5] vs. 58.0 [39.0-73.0] years, P<0.0001), had a longer interval from admission to therapy (Median: 2.3 [95%CI: 1.0-5.0] vs. 4.0 [2.0-12.0] hours, P<0.0001), and more frequently had co-morbid conditions (39.1% vs. 62%, P<0.0001). Meningococcal meningitis decreased by 66% (P<0.0001), whereas meningitis by Listeria monocytogenes increased by 110% (P=0.0007) in period II. There were no differences in the overall case-fatality and post-meningitic sequelae rates between both periods. CONCLUSIONS BM in adult patients has substantially changed over 29 years in terms of population affected, aetiology, and management, but not in terms of its overall mortality rate and appearance of post-meningitic sequelae.

Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome

BackgroundSpontaneous meningitis caused by gram-negative bacilli in adult patients is uncommon and poorly characterized. Our objective is to describe and compare the characteristics and the outcome of adult patients with spontaneous gram-negative bacilli meningitis (GNBM) and spontaneous meningitis due to other pathogens.MethodsProspective single hospital-based observational cohort study conducted between 1982 and 2006 in a university tertiary hospital in Barcelona (Spain). The Main Outcome Measure: In-hospital mortality.ResultsGram-negative bacilli meningitis was diagnosed in 40 (7%) of 544 episodes of spontaneous acute bacterial meningitis. The most common pathogens were Escherichia coli and Pseudomonas species. On admission, characteristics associated with spontaneous gram-negative bacilli meningitis by multivariate modeling were advanced age, history of cancer, nosocomial acquisition of infection, urinary tract infection as distant focus of infection, absence of rash, hypotension, and a high cerebrospinal fluid white-cell count. Nine (23%) episodes were acquired in the hospital and they were most commonly caused by Pseudomonas. The in-hospital mortality rate was 53%. The mortality rate was higher among patients with Gram-negative bacillary meningitis than among those with other bacterial meningitis and their risk of death was twenty times higher than among patients infected with Neisseria meningitidis (odds ratio 20.47; 95% confidence interval 4.03-103.93; p<0.001).ConclusionsGram-negative bacilli cause 9% of spontaneous bacterial meningitis of known etiology in adults. Characteristics associated with GNBM include advanced age, history of cancer, nosocomial acquisition, and urinary tract infection as distant focus of infection. The mortality rate is higher among patients with gram-negative bacillary meningitis than among those with other bacterial meningitides.

Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study

There are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2-63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made.

CTX-M-15-H30Rx-ST131 subclone is one of the main causes of healthcare-associated ESBL-producing Escherichia coli bacteraemia of urinary origin in Spain

OBJECTIVES The objective of this study was to assess the prevalence and molecular epidemiology of ESBL-producing Escherichia coli causing healthcare-associated (HCA) and community-associated (CA) bacteraemia of urinary origin (BUO) in Spain. METHODS An observational cohort study was conducted at eight hospitals from different Spanish geographical areas (2010-11). BUO episodes (n = 425) were classified as HCA (n = 215) and CA (n = 210), and one blood isolate per episode was collected. Susceptibility testing was performed, ESBLs were screened by double-disc diffusion test and ESBL and OXA-1 genes were characterized (PCR and sequencing). Population structure (phylogenetic groups, XbaI-PFGE and MLST) and ST131 subtyping (PCR) were determined. Virulence genes were detected by PCR and virulence score, profiles and extraintestinal pathogenic E. coli (ExPEC) status calculated. RESULTS ESBL-producing E. coli prevalence was 9.2% (39/425). ESBL-producing E. coli episodes were significantly associated with HCA-BUO episodes [14% (30/215) versus 4.3% (9/210); P = 0.001]. The highest non-susceptibility proportions corresponded to ciprofloxacin (97.4%), amoxicillin/clavulanate (74.4%), co-trimoxazole (69.2%) and tobramycin (61.5%). Of the 39 ESBL-producing E. coli isolates, 34 produced CTX-M enzymes (21 CTX-M-15, 11 CTX-M-14 and 2 CTX-M-1). Fifteen STs were identified, the B2-ST131 clone being the most prevalent (54%; 21/39). All ST131 isolates were ExPEC and had the highest virulence scores, but they showed less diversity in virulence profiles than other STs. The H30Rx subclone accounted for most ST131 isolates (20/21), co-produced CTX-M-15 (20/20) and OXA-1 (19/20) enzymes and was associated with HCA episodes (16/20). CONCLUSIONS The CTX-M-15-ST131-H30Rx subclone is a relevant MDR pathogen causing BUO, mainly HCA episodes. The dominance of this subclone with comparatively less diversity of virulence profiles reflects the spread of a successful and MDR ESBL ST131 lineage in Spain.