Efficacy and safety of colistin plus beta-lactams for bone and joint infection caused by fluoroquinolone-resistant gram-negative bacilli: a prospective multicenter study.

OBJECTIVES: The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort. METHODS: Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate. RESULTS: Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001). CONCLUSIONS: Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.

Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study.

BACKGROUND: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). METHODS: We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. RESULTS: Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality. CONCLUSIONS: In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

How to Handle Concomitant Asymptomatic Prosthetic Joints During an Episode of Hematogenous Periprosthetic Joint Infection, a Multicenter Analysis.

BACKGROUND: Prosthetic joints are at risk of becoming infected during an episode of bacteremia, especially during Staphylocococcus aureus bacteremia. However, it is unclear how often asymptomatic periprosthetic joint infection (PJI) occurs, and whether additional diagnostics should be considered. METHODS: In this multicenter study, we retrospectively analyzed a cohort of patients with a late acute (hematogenous) PJI between 2005-2015 who had concomitant prosthetic joints in situ. Patients without at least 1 year of follow-up were excluded. RESULTS: We included 91 patients with a hematogenous PJI and 108 concomitant prosthetic joints. The incident PJI was most frequently caused by Staphylococcus aureus (43%), followed by streptococci (26%) and Gram-negative rods (18%). Of 108 concomitant prosthetic joints, 13 were symptomatic, of which 10 were subsequently diagnosed as a second PJI. Of the 95 asymptomatic prosthetic joints, 1 PJI developed during the follow-up period and was classified as a "missed" PJI at the time of bacteremia with S. aureus (1.1%). Infected prosthetic joints were younger than the noninfected ones in 67% of cases, and prosthetic knees were affected more often than prosthetic hips (78%). CONCLUSIONS: During an episode of hematogenous PJI, concomitant asymptomatic prosthetic joints have a very low risk of being infected, and additional diagnostic work-up for these joints is not necessary.

Effectiveness and safety of intravenous tocilizumab to treat COVID-19-associated hyperinflammatory syndrome: Covizumab-6 observational cohort.

Although the starting event in COVID-19 is a viral infection some patients present with an over-exuberant inflammatory response, leading to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Since IL-6 plays a critical role in the inflammatory response, we assessed the efficacy and safety of tocilizumab (TCZ) in this single-centre, observational study in all Covid-19 in-patient with a proven SARS-CoV-2 rapidly progressing infection to prevent ALI and ARDS. 104 patients with COVID-19 treated with TCZ had a lower mortality rate (5·8%) compared with the regional mortality rate (11%), hospitalized patient's mortality (10%), and slightly lower than hospitalized patients treated with our standard of care alone (6%). We found that TCZ rapidly decreased acute phase reactants, ferritin and liver release of proteins. D-Dimer decreased slowly. We did not observe specific safety concerns. Early administration of IL6-R antagonists in COVID-19 patients with impending hyperinflammatory response, may be safe and effective treatment to prevent, ICU admission and further complications.

Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: a multicentre retrospective observational cohort study.

BACKGROUND: Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality. METHODS: This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009-15. We evaluated the association between ß-lactam plus aminoglycoside or quinolone combination therapy versus ß-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy. RESULTS: Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64-1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens. CONCLUSIONS: In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections.

In recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR) Pseudomonas aeruginosa has become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options. In vitro and in vivo treatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDR P. aeruginosa infections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other "old" antimicrobials, such as certain ß-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDR P. aeruginosa strains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDR P. aeruginosa, especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.

Ceftazidime, Carbapenems, or Piperacillin-tazobactam as Single Definitive Therapy for Pseudomonas aeruginosa Bloodstream Infection: A Multisite Retrospective Study.

BACKGROUND: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although ß-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. METHODS: A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with ß-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. RESULTS: Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52-2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67-2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). CONCLUSIONS: No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection.

Characteristics and outcome of spontaneous bacterial meningitis in patients with diabetes mellitus.

BACKGROUND: Studies on bacterial meningitis in diabetics patients versus non-diabetics are scarce. In patients with diabetes, bacterial meningitis may have a different presentation, etiology and course. We analyzed and compared the characteristics and outcome of spontaneous BM in adult patients with and without diabetes mellitus (DM). METHODS: We performed a single-center, prospective observational cohort study, conducted between 1982 and 2017, in a tertiary university hospital in Barcelona (Spain). The primary outcome measure was in-hospital mortality. RESULTS: We evaluated 715 episodes of bacterial meningitis; 106 patients (15%) had diabetes mellitus. Patients with diabetes were older (median 67 [IQR 17] vs 49 [IQR 40] years, p <  0.001) and more often had a Charlson comorbidity score of ≥3 (40% vs 15%, p <  0.001). Neck stiffness (56% vs 75%, p <  0.001), headache (41% vs 78%) p <  0.001), nausea and/or vomiting (32% vs 56% p < 0.001), and rash (12% vs 26%, p = 0.007) were less frequent in diabetics, whereas altered mental status was more common. Streptococcus pneumoniae and Listeria meningitis were the most common etiologic agents (24 and 18%, respectively). Listeria was more frequent (18% vs. 10%, p = 0.033), whereas meningococcal meningitis was less frequent (10% vs 32%, p < 0.001). Overall mortality was higher in patients with diabetes (26% vs 16%, p = 0.025) concerning non-diabetics. CONCLUSIONS: Patients with bacterial meningitis and diabetes mellitus are older, have more comorbidities, and higher mortality. S. pneumoniae and L. monocytogenes are the predominant pathogens, Listeria being more common, whereas Neisseria meningitidis is significantly less frequent than in non-diabetics.

The Not-So-Good Prognosis of Streptococcal Periprosthetic Joint Infection Managed by Implant Retention: The Results of a Large Multicenter Study.

BACKGROUND.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using ß-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with ß-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of ß-lactams are confirmed and maybe also a potential benefit from adding rifampin.

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

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-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 Fisher's 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.

Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain.

This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis-multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (n = 101) of the XDR isolates, distantly followed by ST244 (n = 16), ST253 (n = 12), ST235 (n = 8), and ST111 (n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (n = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the ß-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in ß-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.

The Effect of Preoperative Antimicrobial Prophylaxis on Intraoperative Culture Results in Patients with a Suspected or Confirmed Prosthetic Joint Infection: a Systematic Review.

Obtaining reliable cultures during revision arthroplasty is important to adequately diagnose and treat a prosthetic joint infection (PJI). The influence of antimicrobial prophylaxis on culture results remains unclear. Since withholding prophylaxis increases the risk for surgical site infections, clarification on this topic is critical. A systematic review was performed with the following research question: in patients who undergo revision surgery of a prosthetic joint, does preoperative antimicrobial prophylaxis affect the culture yield of intraoperative samples in comparison with nonpreoperative antimicrobial prophylaxis? Seven articles were included in the final analysis. In most studies, standard diagnostic culture techniques were used. In patients with a PJI, pooled analysis showed a culture yield of 88% (145/165) in the prophylaxis group versus 95% (344/362) in the nonprophylaxis group (P = 0.004). Subanalysis of patients with chronic PJIs showed positive cultures in 88% (78/89) versus 91% (52/57), respectively (P = 0.59). In patients with a suspected chronic infection, a maximum difference of 4% in culture yield between the prophylaxis and nonprophylaxis groups was observed. With the use of standard culture techniques, antimicrobial prophylaxis seems to affect cultures in a minority of patients. Along with the known risk of surgical site infections due to inadequate timing of antimicrobial prophylaxis, we discourage the postponement of prophylaxis until tissue samples are obtained in revision surgery. Future studies are necessary to conclude whether the small percentage of false-negative cultures after prophylaxis can be further reduced with the use of more-sensitive culture techniques, like sonication.

Impact of colistin plasma levels on the clinical outcome of patients with infections caused by extremely drug-resistant Pseudomonas aeruginosa.

BACKGROUND: Colistin has a narrow therapeutic window with nephrotoxicity being the major dose-limiting adverse effect. Currently, the optimal doses and therapeutic plasma levels are unknown. METHODS: Prospective observational cohort study, including patients infected by colistin-susceptible P. aeruginosa treated with intravenous colistimethate sodium (CMS). Clinical data and colistin plasma levels at steady-state (Css) were recorded. The primary and secondary end points were clinical cure and 30-day all-cause mortality. RESULTS: Ninety-one patients were included. Clinical cure was observed in 72 (79%) patients. The mean (SD) Css was 1.49 (1.4) mg/L and 2.42 (1.5) mg/L (p = 0.01) in patients who achieved clinical cure and those who not, respectively. Independent risk factors for clinical failure were male sex (OR 5.88; 95% CI 1.09-31.63), APACHE II score (OR 1.15; 95% CI 1.03-1.27) and nephrotoxicity at the EOT (OR 9.13; 95% CI 95% 2.06-40.5). The 30-day mortality rate was 30.8%. Risk factors for 30-day mortality included the APACHE II score (OR 1.98; 95% CI 1-1.20), the McCabe score (OR 2.49; 95% CI 1.14-5.43) and the presence of nephrotoxicity at the end of treatment (EOT) (OR 3.8; 95% CI 1.26-11.47). CONCLUSION: In this series of patients with infections caused by XDR P. aeruginosa infections, Css is not observed to be related to clinical outcome.

Executive summary of management of prosthetic joint infections. Clinical practice guidelines by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

The incidence of prosthetic joint infection (PJI) is expected to increase in the coming years. PJI has serious consequences for patients, and high costs for the health system. The complexity of these infections makes it necessary to organize the vast quantity of information published in the last several years. The indications for the choice of a given surgical strategy and the corresponding antimicrobial therapy are specifically reviewed. The authors selected clinically relevant questions and then reviewed the available literature in order to give recommendations according to a pre-determined level of scientific evidence. The more controversial aspects were debated, and the final composition was agreed at an ad hoc meeting. Before its final publication, the manuscript was made available online in order that all SEIMC members were able to read it and make comments and suggestions.

Methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia in haemodialysis patients.

BACKGROUND: The aim of the study was to determine clinical and microbiological differences between patients with methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia (CRB) undergoing or not undergoing haemodialysis, and to compare outcomes. METHODS: Prospective multicentre study conducted at 21 Spanish hospitals of patients with MRSA bacteraemia diagnosed between June 2008 and December 2009. Patients with MRSA-CRB were selected. Data of patients on haemodialysis (HD-CRB) and those not on haemodialysis (non-HD-CRB) were compared. RESULTS: Among 579 episodes of MRSA bacteraemia, 218 (37.7%) were CRB. Thirty-four (15.6%) were HD-CRB and 184 (84.4%) non-HD-CRB. All HD-CRB patients acquired the infection at dialysis centres, while in 85.3% of the non-HD-CRB group the infection was nosocomial (p < .001). There were no differences in age, gender or severity of bacteraemia (Pitt score); comorbidities (Charlson score ≥ 4) were higher in the HD-CRB group than in the non-HD-CRB group (73.5% vs. 46.2%, p = .003). Although there were no differences in VAN-MIC ≥ 1.5 mg/L according to microdilution, using the E-test a higher rate of VAN-MIC ≥ 1.5 mg/L was observed in HD-CRB than in non-HD-CRB patients (63.3% vs. 44.1%, p = .051). Vancomycin was more frequently administered in the HD-CRB group than in the non-HD-CRB group (82.3% vs. 42.4%, p = <.001) and therefore the appropriate empirical therapy was significantly higher in HD-CRB group (91.2% vs. 73.9%, p = .029). There were no differences with regard to catheter removal (79.4% vs. 84.2%, p = .555, respectively). No significant differences in mortality rate were observed between both groups (Overall mortality: 11.8% vs. 27.2%, p = .081, respectively), but there was a trend towards a higher recurrence rate in HD-CRB group (8.8% vs. 2.2%, p = .076). CONCLUSIONS: In our multicentre study, ambulatory patients in chronic haemodialysis represented a significant proportion of cases of MRSA catheter-related bacteraemia. Although haemodialysis patients with MRSA catheter-related bacteraemia had significantly more comorbidities and higher proportion of strains with reduced vancomycin susceptibility than non-haemodialysis patients, overall mortality between both groups was similar.

Appropriate Duration of Antimicrobial Treatment for Prosthetic Joint Infections: A Narrative Review.

Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.

Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT.

Infection of a native joint, commonly referred to as septic arthritis, is a medical emergency because of the risk of joint destruction and subsequent sequelae. Its diagnosis requires a high level of suspicion. These guidelines for the diagnosis and treatment of septic arthritis in children and adults are intended for use by any physician caring for patients with suspected or confirmed septic arthritis. They have been developed by a multidisciplinary panel with representatives from the Bone and Joint Infections Study Group (GEIO) belonging to the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Paediatric Infections (SEIP) and the Spanish Society of Orthopaedic Surgery and Traumatology (SECOT), and two rheumatologists. The recommendations are based on evidence derived from a systematic literature review and, failing that, on the opinion of the experts who prepared these guidelines. A detailed description of the background, methods, summary of evidence, the rationale supporting each recommendation, and gaps in knowledge can be found online in the complete document.

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.