Efficacy of mupirocin, neomycin and octenidine for nasal Staphylococcus aureus decolonisation: a retrospective cohort study.

BACKGROUND: Periprosthetic joint infection (PJI) causes significant morbidity. Methicillin sensitive Staphylococcus aureus (MSSA) is the most frequent organism, and the majority are endogenous. Decolonisation reduces PJIs but there is a paucity of evidence comparing treatments. Aims; compare 3 nasal decolonisation treatments at (1) achieving MSSA decolonisation, (2) preventing PJI. METHODS: Our hospital prospectively collected data on our MSSA decolonisation programme since 2013, including; all MSSA carriers, treatment received, MSSA status at time of surgery and all PJIs. Prior to 2017 MSSA carriers received nasal mupirocin or neomycin, from August 2017 until August 2019 nasal octenidine was used. RESULTS: During the study period 15,958 primary hip and knee replacements were performed. 3200 (20.1%) were MSSA positive at preoperative screening and received decolonisation treatment, 698 mupirocin, 1210 neomycin and 1221 octenidine. Mupirocin (89.1%) and neomycin (90.9%) were more effective at decolonisation than octenidine (50.0%, P < 0.0001). There was no difference in PJI rates (P = 0.452). CONCLUSIONS: Mupirocin and neomycin are more effective than octenidine at MSSA decolonisation. There was poor correlation between the MSSA status after treatment (on day of surgery) and PJI rates. Further research is needed to compare alternative MSSA decolonisation treatments.

Lysosomal alkalization to potentiate eradication of intra-osteoblastic Staphylococcus aureus in the bone and joint infection setting.

OBJECTIVES: Beyond intracellular penetration, acidic lysosomal pH might affect the intracellular activity of some antimicrobials. This study evaluated the ability of lysosomotropic alkalizing agents to potentiate the antimicrobial eradication of an intra-osteoblastic Staphylococcus aureus reservoir in the setting of bone and joint infection (BJI). METHODS: MICs of 16 anti-staphylococcal molecules active against methicillin-sensitive S. aureus (MSSA) were evaluated at pH 5 and pH 7. Additionally, the lysosomal alkalizing potential (spectrofluorometry) and cytotoxicity (MTT assay) of hydroxychloroquine, amantadine and ammonium chloride were assessed. The results led to further investigation of clindamycin, cotrimoxazole, daptomycin and levofloxacin-alone or in combination with hydroxychloroquine-in an in vitro model of osteoblast infection. The impact of hydroxychloroquine on autophagy was finally investigated using Western blot detection of two autophagic flux indicators, the LC3 membrane protein and the SQSTM1 cargo protein. RESULTS: Daptomycin, cotrimoxazole, clindamycin and levofloxacin alone significantly decreased the intracellular staphylococcal reservoir (5.12 log10 CFU/100 000 cells) by 0.14 (95%CI 0.01-0.34), 0.25 (95%CI 0.12-0.43), 0.16 (95%CI 0.004-0.39) and 1.18 (95%CI 1.04-1.38) log10 CFU/100 000 cells, respectively (p < 10-3). Adding hydroxychloroquine (20 mg/L) increased intralysosomal pH from 4.8 to 7, and concomitantly the inoculum of each antimicrobial was reduced by 0.50 (95%CI 0.30-0.84), 0.73 (95%CI 0.59-0.96), 0.59 (95%CI 0.46-0.78) and 1.8 (95%CI 1.66-2.1) log10 CFU/100 000 cells, respectively (p < 10-4). Cellular levels of LC3II and SQSTM1 showed that hydroxychloroquine has direct activity on the autophagic flux, fostering the eradication of intracellular S. aureus by antimicrobials. CONCLUSION: At high concentrations, hydroxychloroquine used as an adjuvant to antimicrobials improves eradication of an S. aureus intra-osteoblastic reservoir in our in vitro cell infection model. These findings advocate further in vivo evaluation of alkalization efficacy and tolerance in S. aureus BJI.

Native joint infections in Iceland 2003-2017: an increase in postarthroscopic infections.

OBJECTIVES: Nationwide study on the epidemiology, clinical characteristics and outcomes among patients with native joint infection (NJI) in Iceland, 2003-2017. METHODS: All positive synovial fluid culture results in Iceland were identified and medical records reviewed. RESULTS: A total of 299 NJI (40 children and 259 adults) were diagnosed in Iceland in 2003-2017, with a stable incidence of 6.3 cases/100 000/year, but marked gender difference among adults (33% women vs 67% men, p<0.001). The knee joint was most commonly affected, and Staphylococcus aureus was the most common isolate in both adults and children, followed by various streptococcal species in adults and Kingella kingae in children. NJI was iatrogenic in 34% of adults (88/259) but comprised 45% among 18-65 years and a stable incidence. Incidence of infections following arthroscopic procedures in adults increased significantly compared with the previous decade (9/100 000/year in 1990-2002 vs 25/100 000/year in 2003-2017, p<0.01) with no significant increase seen in risk per procedure. The proportion of postarthroscopic NJI was 0.17% overall but 0.24% for knee arthroscopy. Patients with postarthroscopic infection were more likely to undergo subsequent arthroplasty when compared with other patients with NJI (p=0.008). CONCLUSIONS: The incidence of NJI in Iceland has remained stable. The proportion of iatrogenic infections is high, especially among young adults, with an increase seen in postarthroscopic infections when compared with the previous decade. Although rare, NJI following arthroscopy can be a devastating complication, with significant morbidity and these results, therefore, emphasise the need for firm indications when arthroscopic treatment is considered.

First report of Kingella kingae diagnosed in pediatric bone and joint infections in Morocco.

BACKGROUND: The progress of diagnostic strategies and molecular methods improved the detection of Kingella kingae in bone and joint infections, and now, Kingella kingae is being increasingly recognized as the most frequent cause of bone and joint infection BJI in early childhood. The main objective of this prospective study is to report the frequency of Kingella Kingae in negative culture bone and joint pediatric infections, and to describe the clinical and biologic features of these children. METHODS: From December 2016 to June 2019, we selected all hospitalized patients with suspected BJI. When culture was negative on the fifth day, children under 10 years were subsequently included in the study, and PCR assay was performed systematically for researching K. kingae specific gene cpn60. Microbial culture and identification were made using standard bacteriological methods. The demographics, clinical, laboratory, radiographic and clinical features were reviewed from medical records. RESULTS: We enrolled 65 children with culture negative BJI, 46 of them having under 10 years old have been screened for the cpn60 gene. Thus, the gene encoding Kingella kingae was positive for 27 BJI cases (58.7%). The mean age of children was 3.02 years, 55.6% were aged 6 months-4 years and 29.6% of them were aged 5-10 years. The male to female ratio was 1.7 and 16 cases (59.26%) occurred during the fall-winter period. The most frequent BJI type was septic arthritis (77.8%) and the most affected sites were knee (51.9%) and hip (37.0%). We recorded a mild clinical picture with normal to mildly raised inflammatory markers. All patients had good clinical and functional outcomes, with no serious orthopedic sequelae.. CONCLUSION: K kingae is an important pathogen of culture-negative BJI in Moroccan children. PCR testing should be performed in culture-negative cases of children not only in the typical age range of 6 months to 4 years. When implemented in the routine clinical microbiology laboratory, a specific K. kingae PCR assay can provide a better diagnostic performance of BJI.

Adherence to oral antibiotic therapy in patients with bone and joint infection: A pilot study.

OBJECTIVES: The management of bone and joint infections (BJI) is complex and requires prolonged antimicrobial therapy. Few data exist on adherence to anti-infectious treatment other than HIV, and none on BJI, even though compliance is considered as a major determinant of clinical outcome. This work aimed at evaluating adherence to oral antimicrobial treatment in patients with BJI. PATIENTS AND METHODS: This is a prospective observational blinded pilot study evaluating adherence by a 6-item questionnaire at 6 weeks (W6) and 3 months (M3) post-surgery. The primary endpoint was the proportion of patients with high, moderate and poor adherence at W6. Secondary endpoints included change in adherence between W6 and M3, and the exploration of potential variables influencing adherence. RESULTS: Analysis was performed on 65 questionnaires obtained from 43 patients including 35 with device-associated BJI. At W6, 11 out of 34 patients were highly adherent to oral antibiotic therapy, 22 moderately adherent and 1 poorly adherent. There was no significant change in adherence to antibiotic therapy between W6 and M3. The only variable significantly associated with the level of adherence at W6 and M3 was the number of daily doses of antibiotic (P=0.04 and 0.02 at W6 and M3, respectively). CONCLUSIONS: This study provided a snapshot of patients' adherence in BJI. Adherence to antibiotic therapy appeared to be stable up to 3 months and a higher number of daily doses of antibiotic was associated with poorer adherence. These observations need to be confirmed in future large-scale studies using electronic pill monitoring systems.

Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study.

OBJECTIVES: An important clindamycin-rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration. METHODS: Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin-rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2-6 weeks, followed by an oral regimen. Liquid chromatography-mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route. RESULTS: Comparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p < 0.001) and its median AUC0-8h was 12 times higher after oral intake (37.7 versus 3.1 mg.h/L, p < 0.001). Riv, Rpo and Rf were 2.68, 18.8 and 7.0 respectively. CONCLUSION: The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion.

Role of asymptomatic bacteriuria on early periprosthetic joint infection after hip hemiarthroplasty. BARIFER randomized clinical trial.

PURPOSE: To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture. METHODS: Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. PRIMARY OUTCOME: early-PJI after HHA. RESULTS: Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33-3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15-7.10]). CONCLUSIONS: Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47.

Bone and joint infections caused by Clostridium perfringens: a case series.

The objective of this study was to evaluate antimicrobial therapy outcomes of bone and joint infections (BJI) caused by Clostridium perfringens. We investigated remission of symptoms and the absence of relapse or reinfection during follow-up. Among the 8 patients with C. perfringens BJI, the type of infection was early prosthesis infection (n = 2), osteosynthetic device infection (n = 4), and chronic osteomyeletis (n = 2). Clindamycin-rifampicin combination was given in 4 cases and metronidazole in 4 cases. The overall success rate was 87.5%. Among the 7 patients who completed antibiotic treatment, the success rate was 100%. The clindamycin-rifampicin combination appeared to be effective in patients with C. perfringens BJI.

Severe adverse events during medical and surgical treatment of hip and knee prosthetic joint infections.

INTRODUCTION: The management of prosthetic joint infection requires a complex treatment procedure and can be associated with complications. However, the occurrence of severe adverse events during this intervention has been poorly evaluated. PATIENTS AND METHODS: A 5-year multicentric retrospective study including patients from 3 hospitals in the South-Western France referral center for complex bone and joint infections (Crioac GSO) and treated for hip or knee prosthetic joint infection with 1 or 2-stage implant exchanges. The objective was to describe grade≥3 adverse events, according to the CTCAE classification, occurring within 6 weeks after surgery and to identify their associated factors. RESULTS: One hundred and eighteen patients were identified. We observed 71 severe events in 50 patients (42.3%; 95% confidence interval [CI95%]: 33.8-51.4%). Sixteen severe events were an evolution of the infection. The remaining 55 others (47 grade 3 and 8 grade 4) occurred in 41 patients (34.7%; CI95%: 26.8-43.7%). They were distributed as follows: 27 (49.1%) medical complications, 21 (38.2%) surgical complications and 7 (12.7%) antibiotic-related complications. The main identified risk factor was a two-stage prosthetic exchange with OR=3.6 (CI95% [1.11-11.94], P=0.032). Obesity was limit of significance with OR=3.3 (CI95% [0.9-12.51], P=0.071). Infection with coagulase negative Staphylococcus was a protective factor with OR=0.3 (CI95% [0.12-0.99], P=0.047). CONCLUSION: Severe adverse events are frequent following prosthetic exchange for PJI (34.7%) and are related to the high frequency of comorbidities in this population and to the complex surgical procedures required. The risk factor significantly associated with these events was a two-stage exchange.

Multifocal joint infection caused by Enterococcus gallinarum.

Musculoskeletal infections caused by Enterococcus gallinarum are rare, but due to its multi-drug resistance has gained more and more attention from the scientific community. We report a case of a 81-year-old immunocompetent Caucasian female with a multifocal joint infection caused by this agent. Shoulder arthrocentesis and two different blood cultures were used to identify this vancomycin-resistant agent in a symptomatic patient. After surgical debridement and 8 weeks of antibiotherapy with ampicillin (1000 mg IV every 6 h), the clinical and laboratory findings were all remarkably improved after treatment. After 2 years follow-up, the patient had no recurrence.

Isolation of clinically significant microorganisms from prosthetic joint tissue using BacT/ALERT paediatric blood culture bottles compared with solid culture media and enrichment broth.

The diagnosis of prosthetic joint infections and isolation of causative microorganisms has been found to be challenging in microbiology laboratories due to low sensitivity of microbiological culture. The aim of this study was to compare the use of conventional culture methods with the use of both enrichment broth and BacT/ALERT paediatric blood culture bottles, for the diagnosis of prosthetic joint infections. A total of 121 specimens from 44 patients were processed using three methods of microbiological culture: solid media, enrichment broth and paediatric bottles. The paediatric bottle method had a significantly lower (p<0.0001) time to detection than the standard solid media method, and was significantly more sensitive than solid media when used independently (93.33%, CI 83.27-98.09, vs 60.00%, CI 45.43-73.33). The combination use of solid media with paediatric bottles was found to be superior to the conventional solid media method and combination use with enrichment broth.

Rapid direct detection of pathogens for diagnosis of joint infections by MALDI-TOF MS after liquid enrichment in the BacT/Alert blood culture system.

Pathogen identification is a critical step during diagnosis of infectious diseases. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight mass spectrometry (MALDI-TOF-MS) has become the gold standard for identification of microorganisms cultured on solid media in microbiology laboratories. Direct identification of microbes from liquid specimen, circumventing the need for the additional overnight cultivation step, has been successfully established for blood culture, urine and liquor. Here, we evaluate the ability of MALDI-TOF MS for direct identification of pathogens in synovial fluid after liquid enrichment in BacT/Alert blood culture bottles. Influence of synovial specimen quality on direct species identification with the MALDI BioTyper/Sepsityper was tested with samples inoculated from pretested native synovia with concomitant inoculation of blood or pus, or highly viscous fluid. Here, we achieved >90% concordance with culture on solid medium, and only mixed-species samples posed significant problems. Performance in routine diagnostics was tested prospectively on bottles inoculated by treating physicians on ward. There, we achieved >70% concordance with culture on solid media. The major contributors to test failure were the absence of a measurable mass signal and mixed-specimen samples. The Sepsityper workflow worked well on samples derived from BacT/Alert blood culture bottles inoculated with synovial fluid, giving concordant results to identification from solid media. Host remnant material in the inoculum, such as blood or pus, had no detrimental effect on identification score values of the BioTyper system after processing with the Sepsityper workflow, and neither had the initial viscosity of the synovial sample.

Does Training Innate Immunity Confer Broad-spectrum Protection Against Bone and Joint Infection in a Mouse Model?

BACKGROUND: The innate immune system can recall previous immunologic challenges and thus respond more effectively to subsequent unrelated challenges, a phenomenon called trained immunity. Training the innate immune system before surgery might be a potential option to prevent bone and joint infection. QUESTIONS/PURPOSES: (1) Does the training process cause adverse effects such as fever or organ injury? (2) Does training the innate immune system confer broad-spectrum protection against bone and joint infection in a mouse model? (3) Does trained immunity remain effective for up to 8 weeks in this mouse model? METHODS: After randomization and group information blinding, we trained the innate immune system of C57BL/6 mice (n = 20 for each group) by intravenously injecting them with either 0.1 mg of zymosan (a toll-like receptor 2 agonist), 0.1 mg of lipopolysaccharide (a toll-like receptor 4 agonist), or normal saline (control). For assessing the host response and possible organ injury after training and infection challenge, we monitored rectal temperature, collected blood to determine leukocyte counts, and performed biochemical and proinflammatory cytokine analyses. After 2 weeks, we then assessed whether trained immunity could prevent infections in an intraarticular implant model subjected to a local or systemic challenge with a broad spectrum of bacterial species (Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Streptococcus pyogenes, or Pseudomonas aeruginosa) in terms of culture-positive rate and colony counts. The proportion of culture-positive joint samples from trained and control groups were compared after 4 weeks. Finally, we increased the interval between training and bacterial challenge up to 8 weeks to assess the durability of training efficacies. RESULTS: Training with zymosan and lipopolysaccharide caused mild and transient stress in host animals in terms of elevated rectal temperature and higher blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase levels. Trained mice had fewer culture-positive joint samples after local inoculation with S. aureus (control: 100% [20 of 20]; zymosan: 55% [11 of 20], relative risk 0.55 [95% CI 0.37 to 0.82]; p = 0.001; lipopolysaccharide: 60% [12 of 20], RR 0.60 [95% CI 0.42 to 0.86]; p = 0.003) and systemic challenge with S. aureus (control: 70% [14 of 20]; zymosan: 15% [3 of 20], RR 0.21 [95% CI 0.07 to 0.63]; p = 0.001; lipopolysaccharide: 15% [3 of 20], RR 0.21 [95% CI 0.07 to 0.63]; p = 0.001) than controls. We observed similar patterns of enhanced protection against local and systemic challenge of E. coli, E. faecalis, S. pyogenes, and P. aeruginosa. Zymosan-trained mice were more effectively protected against both local (control: 20 of 20 [100%], zymosan: 14 of 20 [70%], RR 0.70 [95% CI 0.53 to 0.93]; p = 0.02) and systemic (control: 70% [14 of 20]; zymosan: 30% [6 of 20], RR 0.43 [95% CI 0.21 to 0.89]; p = 0.03) challenge with S. aureus for up to 8 weeks than controls. CONCLUSIONS: Trained immunity confers mild stress and broad-spectrum protection against bone and joint infection in a mouse model. The protection conferred by immunity training lasted up to 8 weeks in this mouse model. The results of the current research support further study of this presurgical strategy to mitigate bone and joint infection in other large animal models. CLINICAL RELEVANCE: If large animal models substantiate the efficacy and safety of presurgical immunity training-based strategies, clinical trials would be then warranted to translate this strategy into clinical practice.

Ultrasound frequency of sonication applied in microbiological diagnostics has a major impact on viability of bacteria causing PJI.

OBJECTIVES: Sonication of explanted prosthesis constitutes an element of microbiological diagnostics. The aim of performing this procedure is to remove biofilm and to increase sensitivity of diagnostics. Ultrasound used in medical purposes are low-frequency and low-intensity. With this wide range of frequency which can be used in sonication process it is necessary to find the golden mean between biofilm dislodging and planktonic bacteria sparing. MATERIALS AND METHODS: The aim of this study was to determine the least harming low-intensity ultrasound frequency (35 kHz, 40 kHz or 53 kHz) used during sonication process with other parameters constant. Four bacteria species were examined: S. aureus, E. faecalis, E. coli, K. pneumoniae. Number of microbiological studies (n) for each group (g) counted 40 specimens (based on scheme 1 bacteria type - 4 groups, 40 studies each). RESULTS: A detailed analysis of gathered data was conducted. Based on study findings following conclusions were drawn. Sonication has a significant and negative impact on survival of sonicated planktonic bacteria. Part of bacteria in planktonic state are damaged/killed by ultrasound, which is demonstrated by lower CFU count in sonicated samples versus control group. CONCLUSIONS: Optimal ultrasound frequencies for sonication of S. aureus, P. aeruginosa and E. coli are 35 kHz and 40 kHz. Ultrasound frequencies used in sonication process (35 kHz, 40 kHz, 53 kHz) of E. coli showed same impact on bacteria survival. It is crucial to perform further assessment of ultrasound parameters on clinical effects of sonication used in PJI diagnostics.

Multidisciplinary management of the bone and joint infection complicating treatment of an open fracture of the lower limb.

Bone and joint infections (BJI) of the lower limb can cause functional sequelae and in some cases have an impact on patient's life prognostic. One of the main objectives of multidisciplinary consultation team meetings (MTM) in the treatment of bone and joint infections is to provide an appropriate medical-surgical care, pooling skills of different organ specialists: infectious disease physicians, microbiologists, orthopedic surgeons and plastic surgeons. Treatment is based on aggressive debridement, bone stabilization, adequate antibiotic therapy, long-term coverage of the loss of skin substance and close clinical monitoring. The authors present their multidisciplinary diagnostic and therapeutic approaches to BJI complicating an open fracture at a referent center in the management of complex bone and joint infections.

Accuracy of blood-tests and synovial fluid-tests in the diagnosis of periprosthetic joint infections.

INTRODUCTION: Periprosthetic joint infection (PJI) is one of the most complex complications following total joint arthroplasty. Despite significant progress in recent years, the use of blood and synovial biomarkers to diagnose PJI remains a challenge. AREAS COVERED: A combination of serological, synovial, microbiological, histological, and radiological investigations is suggested by consensus and international guidelines. Novel biomarkers and molecular methods have shown promise in recent years. The purpose of this review is to provide an update about the biomarkers used to diagnose PJI and highlight their sensitivity and specificity. In addition, guidance on the diagnostic steps and clinical workflow will be included. EXPERT OPINION: The diagnostic algorithm developed and validated by the international consensus meeting group is still the most valuable resource to approach PJI diagnosis. The current combination of blood and synovial biomarkers yield acceptable results and good performance. However, there is a need for new biomarkers and further research to understand the limitations of current tests better, as well as explore new options such as alpha-defensin, D-dimer, interleukin-6, and leukocyte esterase.

Efficacy and Therapeutic Drug Monitoring of Continuous Beta-Lactam Infusion for Osteoarticular Infections Caused by Fluoroquinolone-Resistant Pseudomonas aeruginosa: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: Osteoarticular infections (OIs) caused by fluoroquinolone-resistant Pseudomonas aeruginosa, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, have poor outcomes. We evaluated the outcomes of an optimized strategy of continuous beta-lactam infusion (BL-CI) guided by therapeutic drug monitoring (TDM) for OIs caused by fluoroquinolone-resistant P. aeruginosa. METHODS: A prospective observational study of patients with P. aeruginosa OIs in a hospital-based BL-CI program (2016-2018) was carried out. TDM targeting free BL concentrations in plasma (fCss) of at least 3-4 × MIC was performed. We compared failure rates between patients with OIs caused by fluoroquinolone-resistant strains who were treated with BL-CI, with or without colistin, and patients with OIs caused by fluoroquinolone-susceptible strains who were treated with ciprofloxacin. RESULTS: Fifty-two patients were included in the study, 19 (36.5%) of whom had OIs caused by fluoroquinolone-resistant P. aeruginosa (13 (68.4%) MDR/XDR strains; 11 (57.9%) device-related infections). The median duration of BL-CI was 36 days; ten patients (52.6%) received BL-colistin combinations. Eighty-two samples were utilized in the TDM, and most patients were found to have a median fCss of 3-10 × MIC; 17 dose adjustments were performed and eight patients needed dose decreases, five of which were due to chronic kidney disease or acute kidney injury (AKI). BL-CI was well tolerated, with the most frequent adverse event being AKI. Failure occurred to 4 patients (21.1%), which was similar to the failure rate of patients with OIs caused by fluoroquinolone-susceptible P. aeruginosa treated with ciprofloxacin (5/30 [16.7%]) (p = 0.699). TDM was also used in the initial BL treatment of patients with OIs caused by susceptible strains before those patients were switched to treatment with ciprofloxacin alone (33 patients, 110 samples, 19 dose adjustments). CONCLUSIONS: BL-CI used with/without colistin and supported by TDM may be an alternative and effective treatment option for OIs caused by fluoroquinolone-resistant P. aeruginosa, where limited available therapeutic options exist, especially in the setting of multidrug resistance. Future research should elucidate whether this strategy can produce outcomes similar to those of patients treated for OIs caused by fluoroquinolone-susceptible strains.

Strain-specific joint invasion and colonization by Lyme disease spirochetes is promoted by outer surface protein C.

Lyme disease, caused by Borrelia burgdorferi, B. afzelii and B. garinii, is a chronic, multi-systemic infection and the spectrum of tissues affected can vary with the Lyme disease strain. For example, whereas B. garinii infection is associated with neurologic manifestations, B. burgdorferi infection is associated with arthritis. The basis for tissue tropism is poorly understood, but has been long hypothesized to involve strain-specific interactions with host components in the target tissue. OspC (outer surface protein C) is a highly variable outer surface protein required for infectivity, and sequence differences in OspC are associated with variation in tissue invasiveness, but whether OspC directly influences tropism is unknown. We found that OspC binds to the extracellular matrix (ECM) components fibronectin and/or dermatan sulfate in an OspC variant-dependent manner. Murine infection by isogenic B. burgdorferi strains differing only in their ospC coding region revealed that two OspC variants capable of binding dermatan sulfate promoted colonization of all tissues tested, including joints. However, an isogenic strain producing OspC from B. garinii strain PBr, which binds fibronectin but not dermatan sulfate, colonized the skin, heart and bladder, but not joints. Moreover, a strain producing an OspC altered to recognize neither fibronectin nor dermatan sulfate displayed dramatically reduced levels of tissue colonization that were indistinguishable from a strain entirely deficient in OspC. Finally, intravital microscopy revealed that this OspC mutant, in contrast to a strain producing wild type OspC, was defective in promoting joint invasion by B. burgdorferi in living mice. We conclude that OspC functions as an ECM-binding adhesin that is required for joint invasion, and that variation in OspC sequence contributes to strain-specific differences in tissue tropism displayed among Lyme disease spirochetes.

Aumento de Staphylococcus aureus resistente a meticilina y sensible a ciprofloxacino en infecciones osteoarticulares, de piel y tejidos blandos / Increase in methicillin-resistant and ciprofloxacin-susceptible Staphylococcus aureus in osteoarticular, skin and soft tissue infections

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