Antibiotic guidelines coupled with selective reporting of antibiograms.

OBJECTIVES: We reported the impact of internal guidelines coupled with selective reporting of antibiotic susceptibility tests (srAST) on antibiotic adequacy in healthcare facilities. METHODS: This prospective study involved clinicians from three clinics with medical and surgical activities employing a full-time infectious disease (ID) specialist. Internal guidelines were updated in 2016. The clinics were working with the same laboratory, which delivered the srAST introduced in March 2017. Two weeks per month over a 6-month period, all isolated bacterial specimens, empirical antibiotic therapies (EAT) and the documented ones were analyzed. An EAT listed in the guidelines and a documented therapy mentioned in the srAST defined their adequacy. RESULTS: A total of 257 positive bacterial samples were analyzed in 199 patients, for which 106 infections were studied. Of these, 32% were urinary tract infections, 15% were primary bloodstream infections, 11% were bone infections, and 42% were other types of infection. The three main bacteria were Escherichia coli (27%), Staphylococcus aureus (24%), and Enterococcus faecalis (14%). The total number of antibiotic prescriptions was 168, with 75 (45%) EATs and 93 (55%) documented therapies. There were 35/75 (47%) adequate EATs and 86/93 (92%) adequate documented therapies. The ID specialist was not involved in 90/168 (53.5%) prescriptions, of which 43/90 (48%) were adequate, with 21/35 (60%) EATs and 22/86 (25%) documented therapies. There was a statistical correlation between compliance of the EATs with guidelines and of the documented therapy with srAST (p=0.02). CONCLUSION: Combining internal guidelines and srAST led to a high rate of antibiotic adequacy.

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.

Treponematosis in a pre-Columbian hunter-gatherer male from Antofagasta (1830 ± 20 BP, Northern Coast of Chile).

OBJECTIVE: This paper reports a new case of treponemal disease in a pre-Columbian hunter-gatherer inhabiting the desert coast of South America. MATERIALS: A well-preserved adult male skeleton from the "Vertedero Municipal" archaeological cemetery, located near the city of Antofagasta (Northern Chile). METHODS: The skeleton was radiocarbon dated, and isotopic analyses were performed to assess diet and mobility. Lytic and proliferative lesions identified were evaluated macroscopically and radiologically. RESULTS: A radiocarbon date of 1830 ± 20 BP and isotopic values indicating a marine diet and coastal residence were obtained. The cranium shows reactive changes as focal superficial cavitation, radial scarring and nodular cavitation, while the ribs, sternum, clavicles, and scapulae exhibit multiple lytic and proliferative lesions. The right femur has a node while both tibiae show mild anterior cortical thickening with a narrowed medullary cavity. CONCLUSIONS: Cranial lesions are pathognomonic for treponemal disease while postcranial changes are typical, and highly consistent with this pathology. SIGNIFICANCE: The type, morphology, and pattern of lesions make this case a good candidate for venereal syphilis. The case is relevant to the origin of venereal syphilis due to the lifestyle, temporal and ecological context of the individual. LIMITATIONS: Diagnosis of venereal syphilis is based on skeletal lesions; thus, it must be confirmed by molecular analysis. SUGGESTIONS FOR FURTHER RESEARCH: A comprehensive review of cases of pre-Columbian treponemal disease in South America as well as molecular studies are needed to confirm the presence of venereal syphilis in the New World before European contact.

Measurement uncertainty of ß-lactam antibiotics results: estimation and clinical impact on therapeutic drug monitoring.

Background Despite that measurement uncertainty data should facilitate an appropriate interpretation of measured values, there are actually few reported by clinical laboratories. We aimed to estimate the measurement uncertainty of some ß-lactam antibiotics (ß-LA), and to evaluate the impact of reporting the measurement uncertainty on clinicians' decisions while guiding antibiotic therapy. Methods Measurement uncertainty of ß-LA (aztreonam [ATM], cefepime [FEP], ceftazidime [CAZ], and piperacillin [PIP]) values, obtained by an UHPLC-MS/MS based-method, was estimated using the top-down approach called the single laboratory validation approach (EUROLAB guidelines). Main uncertainty sources considered were related to calibrators' assigned values, the intermediate precision, and the bias. As part of an institutional program, patients with osteoarticular infections are treated with ß-LA in continuous infusion and monitored to assure values at least 4 times over the minimal inhibitory concentration (4×MIC). We retrospectively evaluated the impact of two scenarios of laboratory reports on clinicians' expected decisions while monitoring the treatment: reports containing only the ß-LA values, or including the ß-LA coverage intervals (ß-LA values and their expanded measurement uncertainties). Results The relative expanded uncertainties for ATM, FEP, CAZ and PIP were lower than 26.7%, 26.4%, 28.8%, and 25.5%, respectively. Reporting the measurement uncertainty, we identified that clinicians may modify their decision especially in cases where 4×MIC values were within the ß-LA coverage intervals. Conclusions This study provides a simple method to estimate the measurement uncertainty of ß-LA values that can be easily applied in clinical laboratories. Further studies should confirm the potential impact of reporting measurement uncertainty on clinicians' decision-making while guiding antibiotic therapy.

Comparison of Musculoskeletal Infections due to Nontyphoidal Salmonella Species and Staphylococcus aureus in Immunocompetent Children.

BACKGROUND: Nontyphoidal Salmonella species (NTS) rarely cause musculoskeletal infections in healthy children. Data on NTS musculoskeletal infections in healthy children are limited. No previous studies have directly compared children with NTS musculoskeletal infections with those with Staphylococcus aureus. METHODS: This was a case-control study of children 30 days-18 years old seen at Texas Children's Hospital between 2010 and 2017 with NTS musculoskeletal infections. Controls were children with S. aureus musculoskeletal infections matched on date of infection. Patients with known predisposing conditions were excluded. Demographic and clinical risk factors between the 2 groups were compared. RESULTS: From 2010 to 2017, 27 cases of NTS musculoskeletal infections were identified, 12 (46.0%) of which occurred in healthy children. The control group had 53 patients. Predictors of NTS musculoskeletal infections included exposure to reptiles [odds ratio (OR) 8.50, 95% confidence interval (CI): 11.24-58.23] and preceding gastrointestinal symptoms (OR 5.63, 95% CI: 1.45-21.89). Children with NTS musculoskeletal infections had greater odds of pelvic and/or spinal involvement than S. aureus controls (OR 5.32, 95% CI: 1.42-20.13). Complications occurred in 16.7% of NTS cases versus 32% of S. aureus controls. CONCLUSIONS: Healthy children with NTS musculoskeletal infections more frequently report reptile exposure and preceding gastrointestinal symptoms and have pelvic and spinal involvement compared with children with musculoskeletal infections due to S. aureus. NTS should be considered as a potential cause of musculoskeletal infections in children with these risk factors. In contrast to previous case reports and case series, children with NTS musculoskeletal infections had a low rate of complications.

Clinical Use of Colistin in Biofilm-Associated Infections.

Biofilm is an adaptive bacterial strategy whereby microorganisms become encased in a complex glycoproteic matrix. The low concentration of oxygen and nutrients in this environment leads to heterogeneous phenotypic changes in the bacteria, with antimicrobial tolerance being of paramount importance. As with other antibiotics, the activity of colistin is impaired by biofilm-embedded bacteria. Therefore, the recommendation for administering high doses in combination with a second drug, indicated for planktonic infections, remains valid in this setting. Notably, colistin has activity against metabolically inactive biofilm-embedded cells located in the inner layers of the biofilm structure. This is opposite and complementary to the activity of other antimicrobials that are able to kill metabolically active cells in the outer layers of the biofilm. Several experimental models have shown a higher activity of colistin when used in combination with other agents, and have reported that this can avoid the emergence of colistin-resistant subpopulations. Most experience of colistin in biofilm-associated infections comes from patients with cystic fibrosis, where the use of nebulized colistin allows high concentrations to reach the site of the infection. However, limited clinical experience is available in other scenarios, such as osteoarticular infections or device-related central nervous system infections caused by multi-drug resistant microorganisms. In the latter scenario, the use of intraventricular or intrathecal colistin also permits high local concentrations and good clinical results. Overall, the efficacy of intravenous colistin seems to be poor, but its association with a second antimicrobial significantly increases the response rate. Given its activity against inner bioflm-embedded cells, its possible role in combination with other antibiotics, beyond last-line therapy situations, should be further explored.

Osteomielitis Aguda: Características Clínicas, Radiológicas y de Laboratorio / Acute Osteomyelitis: Clinical, Radiological and Laboratory Characteristics

Resumen Se efectuó una revisión de la literatura sobre ésta patología incapacitante y frustrante, tanto para el paciente como el médico tratante, ya que sus manifestaciones clínicas son similares a otros cuadros infecciosos. Además, se exponen conceptos acerca de su definición, clasificación y etiología, para actualizar de manera breve el proceso infeccioso. Los estudios por imágenes proveen información adicional ante la sospecha clínica; pero ninguna técnica puede confirmar o excluir en forma absoluta la presencia de osteomielitis, especialmente cuando existen implantes u osteopatía. Se debe evaluar minuciosamente la elección de cada uno de estos métodos, teniendo en cuenta su disponibilidad y qué se pretende hacer con ellos. Nunca debe postergarse la realización de procedimientos invasivos, que en general son necesarios para arribar al diagnóstico. El principal objetivo es indagar dentro de los distintas prácticas diagnósticas, para que de ésta manera el equipo médico utilice herramientas adecuadas para determinar si se trata de ésta afección en los distintos centros de trabajo y así utilizar de manera eficaz los recurso disponibles en cada nivel de atención; brindando así un tratamiento precoz y evitar las complicaciones pertinentes a corto y a largo plazo.

Abstract Osteomylitis is a painful and incapacitating disease which is frustrating for the patient and for the doctor treating it. Its symptoms are very similar to other types of infections. The definition, classification and etiology will be briefly explained in order to provide a better understanding about this infectious disease. Medical Imaging Procedures provide aditional information when the presence of the disease is suspected. There is not a certain technique that can confirm or exclude its existence, especially when implants or osteopathy have taken place. Any choice of method must be minutely assessed, keeping in mind its availability and what you expect from it. The invasive procedures should never be postponed, due to the importance they have when getting a diagnosis. The main objective is to look into different diagnoses, so the medical team can have the appropriate tools to determine the presence of the illness in a working area. Using the tools in an efficient way and taking advantage of the resources available, can provide preventive and early treatment in order to avoid short and long term complications.

Encapsulation of green tea polyphenol by pH responsive, antibacterial, alginate microgels used for minimally invasive treatment of bone infection.

The treatment of bone infection requires drug carriers take large number of cargo, be antibacterial, promote proliferation and differentiation of osteoblasts. Herein, we proposed a strategy of preparing pH responsive, antibacterial, multistage structured microspheres encapsulated with green tea polyphenol used for minimally invasive treatment of bone infection. Tea polyphenol (TP) were encapsulated by porous silica nanospheres (SiO2 NSs). Then, sodium alginate (SA) microgel spheres (MSs) were prepared to encapsulate a lot of TP loaded SiO2 NSs. The outer layer of obtained TP@SiO2@SA microgel spheres were further wrapped by pH sensitive CaCO3. Mineral out-layer of the composite microspheres is used to neutralize the acidic environment caused by bacterial infection. At the same time, encapsulated TP is released pH sensitively to resist oxidative stress. Our results exhibited excellent drug delivery properties including drug loading efficiency (DLE) of 92.96% and drug loading content (DLC) of 19.62%. Besides, results demonstrated that TP@SiO2@SA@CaCO3 MSs can effectively kill Staphylococcus aureus and promote proliferation and differentiation of osteoblasts under stimulation of H2O2 at pH = 5.5.

Infecciones osteoarticulares en un hospital pediátrico de alta complejidad: epidemiología y características clínicas asociadas con bacteriemia / Osteoarticular infections in a tertiary care children's hospital: Epidemiology and clinical characteristics in association with bacteremia

Introducción. Las infecciones osteoarticulares son una importante causa de morbilidad y pueden presentar bacteriemia. La epidemiología de estas infecciones se ha modificado en los últimos años. Objetivos. Describir las características epidemiológicas, clínicas y evolutivas de los niños con infecciones osteoarticulares y comparar los pacientes con bacteriemia con los que no la presentaron. Población y métodos. Cohorte retrospectiva. Se incluyeron pacientes menores de 18 años, admitidos en el Hospital Juan P. Garrahan entre el 1/1/2016 y el 31/12/2016 con sospecha de infecciones osteoarticulares en quienes se hubiese realizado artrocentesis y/o biopsia articular. Se excluyeron niños con patología previa. Se compararon las características clínicas y de laboratorio según tuvieran bacteriemia o no. Se utilizó Stata 10. Resultados. N: 62. La mediana de edad fue 59.5 meses (rango intercuartilo -RIC- 24-84). Presentaron fiebre 44 pacientes (70%). Predominaron las artritis (54 pacientes, 87%). Se identificó un agente etiológico en 29 pacientes (47%). Predominó Staphylococcus aureus (n: 20, 32%). Tuvieron bacteriemia 15 de ellos (24%). Recibieron clindamicina como tratamiento empírico 56 pacientes (90%). La mediana de tratamiento endovenoso fue 7 días (RIC 5-11) y de internación, 7 días (RIC 4-12). Los pacientes con bacteriemia tuvieron menor edad (26 meses vs. 60, p < 0,05), mayor valor de proteína C reactiva inicial (101 vs. 33 U/L, p < 0,05), menor valor de hemoglobina al ingresar (10,8 g/dl vs. 12.5 g/dl, p 0,04) y mayor frecuencia de fiebre (100% vs. 57%, p < 0,05). Conclusiones. Predominó Staphylococcus aureus. Los niños con bacteriemia tuvieron menor edad, mayor valor de proteína C reactiva, menos hemoglobina al ingresar y, más frecuentemente, fiebre.

Introduction. Osteoarticular infections are an important cause of morbidity and may present with bacteremia. The epidemiology has changed in recent years. Objectives. To describe the epidemiological, clinical, and evolutionary characteristics of children with osteoarticular infections and compare patients with and without bacteremia. Population and methods. Retrospective cohort. Patients younger than 18 years admitted between January 1st, 2016 and December 31st, 2016 suspected of osteoarticular infections who had undergone an arthrocentesis and/or joint biopsy were included. Clinical and laboratory characteristics were compared between patients with and without bacteremia. The Stata 10 software was used.Results. N: 62. Patients' median age was 59.5 months (interquartile range [IQR]: 24-84). Fever developed in 44 patients (70%). Arthritis predominated (54 patients, 87%). An etiologic agent was identified in 29 patients (47%). Staphylococcus aureus was prevalent (n: 20, 32%). Among these, 15 developed bacteremia (24%). Clindamycin was administered to 56 patients (90%) as empirical therapy. The median intravenous treatment duration was 7 days (IQR: 5-11) and the median length of stay, 7 days (IQR: 4-12). Patients with bacteremia were younger (26 months versus 60 months, p < 0.05), had a higher baseline C-reactive protein level (101 U/L versus 33 U/L, p < 0.05), a lower hemoglobin level at the time of admission (10.8 g/dL versus 12.5 g/dL, p = 0.04), and a higher frequency of fever (100% versus 57%, p < 0.05).Conclusions. Staphylococcus aureus was prevalent. Children with bacteremia were younger, had a higher C-reactive protein level, a lower hemoglobin level at the time of admission, and 100% presented fever

Association of Vancomycin MIC and Molecular Characteristics with Clinical Outcomes in Methicillin-Susceptible Staphylococcus aureus Acute Hematogenous Osteoarticular Infections in Children.

Strains of methicillin-resistant Staphylococcus aureus (MRSA), particularly those belonging to the USA300 pulsotype, have been well described to cause severe osteoarticular infections (OAIs). A vancomycin MIC of ≥1.5 µg/ml has been demonstrated to contribute to disease severity in adults with MRSA and even methicillin-susceptible S. aureus (MSSA) bacteremia. Little data exist describing the outcomes of MSSA OAIs in terms of molecular characteristics and vancomycin MIC. All patients/isolates were chosen from a surveillance study at Texas Children's Hospital (TCH). S. aureus OAI isolates were identified from 2011 to 2016 and subjected to vancomycin Etests, pulsed-field gel electrophoresis (PFGE), and PCR to determine Panton-Valentine leucocidin (PVL) production and agr group. Two hundred fifty-two cases of S. aureus OAI were identified; 183 cases were MSSA (72.6%). During the study period, a decrease in the proportion of cases secondary to MRSA was observed, declining from 37.8% to 15.9% (P = 0.02). Of the MSSA isolates, 26.2% and 23.5% were USA300 and PVL positive, respectively. An increase in the proportion of MSSA isolates with a vancomycin MIC of ≥1.5 µg/ml occurred in the study period (P = 0.004). In MSSA, an elevated vancomycin MIC was associated with multiple surgical procedures and venous thromboses, even when adjusting for empirical ß-lactam use. An increase in vancomycin MIC was noted among isolates belonging to agr group 4 during the study period. Methicillin resistance is declining among S. aureus OAI isolates at TCH. Simultaneously, vancomycin Etest MICs are increasing among MSSA isolates. Vancomycin MICs of ≥2 µg/ml are associated with adverse clinical outcomes in MSSA irrespective of antibiotic choice, suggesting that this may be a surrogate for organism virulence.

Osteoarticular infections in a tertiary care children's hospital: Epidemiology and clinical characteristics in association with bacteremia. / Infecciones osteoarticulares en un hospital pediátrico de alta complejidad: epidemiología y características clínicas asociadas con bacteriemia.

INTRODUCTION: Osteoarticular infections are an important cause of morbidity and may present with bacteremia. The epidemiology has changed in recent years. OBJECTIVES: To describe the epidemiological, clinical, and evolutionary characteristics of children with osteoarticular infections and compare patients with and without bacteremia. POPULATION AND METHODS: Retrospective cohort. Patients younger than 18 years admitted between January 1st, 2016 and December 31st, 2016 suspected of osteoarticular infections who had undergone an arthrocentesis and/or joint biopsy were included. Clinical and laboratory characteristics were compared between patients with and without bacteremia. The Stata 10 software was used. RESULTS: N: 62. Patients' median age was 59.5 months (interquartile range [IQR]: 24-84). Fever developed in 44 patients (70%). Arthritis predominated (54 patients, 87%). An etiologic agent was identified in 29 patients (47%). Staphylococcus aureus was prevalent (n: 20, 32%). Among these, 15 developed bacteremia (24%). Clindamycin was administered to 56 patients (90%) as empirical therapy. The median intravenous treatment duration was 7 days (IQR: 5-11) and the median length of stay, 7 days (IQR: 4-12). Patients with bacteremia were younger (26 months versus 60 months, p < 0.05), had a higher baseline C-reactive protein level (101 U/L versus 33 U/L, p < 0.05), a lower hemoglobin level at the time of admission (10.8 g/dL versus 12.5 g/dL, p = 0.04), and a higher frequency of fever (100% versus 57%, p < 0.05). CONCLUSIONS: Staphylococcus aureus was prevalent. Children with bacteremia were younger, had a higher C-reactive protein level, a lower hemoglobin level at the time of admission, and 100% presented fever.

INTRODUCCIÓN: Las infecciones osteoarticulares son una importante causa de morbilidad y pueden presentar bacteriemia. La epidemiología de estas infecciones se ha modificado en los últimos años. OBJETIVOS: Describir las características epidemiológicas, clínicas y evolutivas de los niños con infecciones osteoarticulares y comparar los pacientes con bacteriemia con los que no la presentaron. POBLACIÓN Y MÉTODOS: Cohorte retrospectiva. Se incluyeron pacientes menores de 18 años, admitidos en el Hospital Juan P. Garrahan entre el 1/1/2016 y el 31/12/2016 con sospecha de infecciones osteoarticulares en quienes se hubiese realizado artrocentesis y/o biopsia articular. Se excluyeron niños con patología previa. Se compararon las características clínicas y de laboratorio según tuvieran bacteriemia o no. Se utilizó Stata 10. RESULTADOS: N: 62. La mediana de edad fue 59.5 meses (rango intercuartilo -RIC- 24-84). Presentaron fiebre 44 pacientes (70%). Predominaron las artritis (54 pacientes, 87%). Se identificó un agente etiológico en 29 pacientes (47%). Predominó Staphylococcus aureus (n: 20, 32%). Tuvieron bacteriemia 15 de ellos (24%). Recibieron clindamicina como tratamiento empírico 56 pacientes (90%). La mediana de tratamiento endovenoso fue 7 días (RIC 5-11) y de internación, 7 días (RIC 4-12). Los pacientes con bacteriemia tuvieron menor edad (26 meses vs. 60, p < 0,05), mayor valor de proteína C reactiva inicial (101 vs. 33 U/L, p < 0,05), menor valor de hemoglobina al ingresar (10,8 g/dl vs. 12.5 g/dl, p 0,04) y mayor frecuencia de fiebre (100% vs. 57%, p < 0,05). CONCLUSIONES: Predominó Staphylococcus aureus. Los niños con bacteriemia tuvieron menor edad, mayor valor de proteína C reactiva, menos hemoglobina al ingresar y, más frecuentemente, fiebre.

Beta-lactams in continuous infusion for Gram-negative bacilli osteoarticular infections: an easy method for clinical use.

Continuous infusion (CI) of beta-lactams could optimize their pharmacokinetic/pharmacodynamic indices, especially in difficult-to-treat infections. PURPOSE: To validate an easy-to-use method to guide beta-lactams dosage in CI (formula). METHODS: A retrospective analysis was conducted of a prospectively collected cohort (n = 24 patients) with osteoarticular infections caused by Gram-negative bacilli (GNB) managed with beta-lactams in CI. Beta-lactams dose was calculated using a described formula (daily dose = 24 h × beta-lactam clearance × target "steady-state" concentration) to achieve concentrations above the MIC. We correlated the predicted concentration (Cpred = daily dose/24 h × beta-lactam clearance) with the patient's observed concentration (Cobs) measured by UPLC-MS/MS (Spearman's coefficient). RESULTS: The most frequent microorganism treated was P. aeruginosa (21 cases; 9 MDR). Beta-lactams in CI were ceftazidime (n = 14), aztreonam (7), and piperacillin/tazobactam (3), mainly used in combination (12 with colistin, 5 with ciprofloxacin) and administered without notable side effects. The plasma Cobs was higher overall than Cpred; the Spearman correlation between both concentrations was rho = 0.6 (IC 95%: 0.2-0.8) for all beta-lactams, and rho = 0.8 (IC 95%: 0.4-1) for those treated with ceftazidime. CONCLUSIONS: The formula may be useful in clinical practice for planning the initial dosage of beta-lactams in CI, while we await a systematic therapeutic drug monitoring. The use of beta-lactams in CI was safe.

A short artificial antimicrobial peptide shows potential to prevent or treat bone infections.

Infection of bone is a severe complication due to the variety of bacteria causing it, their resistance against classical antibiotics, the formation of a biofilm and the difficulty to eradicate it. Antimicrobial peptides (AMPs) are naturally occurring peptides and promising candidates for treatment of joint infections. This study aimed to analyze the effect of short artificial peptides derived from an optimized library regarding (1) antimicrobial effect on different bacterial species, (2) efficacy on biofilms, and (3) effect on osteoblast­like cells. Culturing the AMP-modifications with Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus (including clinical isolates of MRSA and MSSA) and Staphylococcus epidermidis identified one candidate that was most effective against all bacteria. This AMP was also able to reduce biofilm as demonstrated by FISH and microcalorimetry. Osteoblast viability and differentiation were not negatively affected by the AMP. A cation concentration comparable to that physiologically occurring in blood had almost no negative effect on AMP activity and even with 10% serum bacterial growth was inhibited. Bacteria internalized into osteoblasts were reduced by the AMP. Taken together the results demonstrate a high antimicrobial activity of the AMP even against bacteria incorporated in a biofilm or internalized into cells without harming human osteoblasts.

A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects.

We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 10(7) colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B or C. Collectively, these results show that our fabricated ANDB scaffolds possess: (1) effective bactericidal activity against methicillin-resistant Staphylococcus aureus, (2) the ability to promote site-specific bone regeneration, and (3) the potential for use in the treatment of infected bone defects.

Local transplantation of bone marrow concentrated granulocytes precursors can cure without antibiotics infected nonunion of polytraumatic patients in absence of bone defect.

PURPOSE: Infected, long bone non-unions present a significant clinical challenge. New and alternative therapies are needed to address this problem. The purposes of this study were to compare the number of circulating granulocyte-macrophage colony-forming units (CFU-GM) in the peripheral blood of polytraumatic patients with infected tibial non-unions and in the peripheral blood of control patients with the hypothesis that their number was decreased in polytraumatic patients; and to treat their infection without antibiotics and with local transplantation of bone marrow concentrated granulocytes precursors. METHODS: Thirty (18 atrophic and 12 hyperthrophic ) infected tibial non-unions (without bone defect) that occurred after open fractures in polytraumatic patients were treated without antibiotics and with percutaneous injection of autologous bone marrow concentrate (BMC) containing granulocytes precursors (CFU-GM). CFU-GM progenitors were assessed in the bone marrow aspirate, peripheral blood, and fracture site of these patients. The number of these progenitors was compared with the CFU-GM progenitors of control patient samples (healthy donors matched for age and gender). Outcome measures were: timing of union, callus formation (radiographs and CT scan), and recurrence of clinical infection. RESULTS: As compared to control patients, the number of CFU GM derived colonies was lower at peripheral blood in patients with infected nonunions. The bone marrow graft injected in nonunions contained after concentration 42 621 ± 20 350 CFU-GM-derived colonies/cc. Healing and cure of infection was observed at six months for 25 patients and at one year follow up for 30 patients. At the median ten year follow-up (range: 5 to 15), only one patient had clinical recurrent infection after healing (between 6 months and last follow-up). CONCLUSION: The peripheral blood of these polytraumatic patients with infected nonunions had a remarkable decrease in CFU-GM-derived colonies as compared with normal controls. Local transplantation of concentrated CFU-GM-derived colonies aspirated from bone marrow allowed cure of infection and healing without antibiotics.

Measurement of ceftazidime concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Application to critically ill patients and patients with osteoarticular infections.

Ceftazidime is an antibiotic belonging to the third generation of the cephalosporin family. It is indicated in the treatment of serious, simple or mixed bacterial infections, and its administration in continuous or intermittent infusion allows optimization of the concentration of antibiotic to keep it above the minimum inhibitory concentration. We developed and validated a chromatographic method by ultra-performance liquid chromatography-tandem mass spectrometry to measure ceftazidime concentration in human plasma. Following extraction with acetonitrile and 1,2-dichloroethane, the chromatographic separation was achieved using an Acquity ® UPLC ® BEH(TM) (2.1 × 100 mm i.d., 1.7 µm) reverse-phase C18 column, with a water-acetonitrile linear gradient containing 0.1% formic acid at a 0.4 mL/min flow rate. Ceftazidime and its internal standard (cefotaxime) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass-to-charge transitions of 547.0 → 467.9/396.1 and 456.0 → 395.8/324.1, respectively. The limit of quantification was 0.58 mg/L and linearity was observed in the range 0.58-160 mg/L. Coefficients of variation and absolute relative biases were <9.8 and 8.4%. The mean recovery for ceftazidime was 74.4 ± 8.1%. Evaluation of the matrix effect showed ion enhancement, and no carry-over was observed. The validated method could be applied to daily clinical laboratory practice to measure the concentration of ceftazidime in plasma.

Treatment principles for Candida and Cryptococcus.

The yeasts Candida and Cryptococcus spp. are important human opportunistic pathogens. Candida spp. rely on skin or mucosal breach to cause bloodstream infection, whereas Cryptococcus spp. exploit depressed cell-mediated immunity characteristic of advanced HIV infection. The treatment for both organisms relies on the administration of rapidly fungicidal agents. In candidaemia, source control is important, with removal of prosthetic material and drainage of collections, as well as hunting for and tailoring therapy to disseminated sites of infection, particularly the eyes and heart. For cryptococcal meningitis, restoration of immune function through antiretroviral therapy (ART) is key, together with careful management of the complications of raised intracranial pressure and relapsed infection, both pre- and post-ART.

[Potential utility of ceftaroline fosamil in osteoarticular infections]. / Utilidad potencial de ceftarolina fosamil en las infecciones osteoarticulares.

Osteoarticular infections (OAI) include a wide-usually complex-spectrum of clinical scenarios. The approach is usually medical-surgical. In addition to this complexity, there is a low grade of evidence in the medical literature on these infections. Nevertheless, it is possible-and necessary-to integrate microbiological, pharmacological, experimental and clinical information to achieve the best possible clinical results. The most appropriate choice of antibiotic therapy largely depends on the clinical scenario and, obviously, on the microorganisms involved. Given the protagonism of staphylococci in OAI, it is appropriate to elucidate the role that could be played by a new antistaphylococcic agent in these infections. For clinicians who manage OAI, the incorporation of ceftaroline represents the recovery of a beta-lactam to treat methicillin-resistant staphylococci. This perspective can be used to guide the potential role of this new antibiotic for the management of OAI in various scenarios and the clinical research required for its introduction in clinical practice.

Superimposed infection in mandibular osteoradionecrosis: diagnosis and outcomes.

BACKGROUND: Radiation therapy can result in osteoradionecrosis (ORN) and mucosal ulceration predisposing to infection. METHODS: Fourteen patients presenting with infectious sequelae related to mandibular ORN were retrospectively reviewed. RESULTS: In most patients, infection followed diagnosis of ORN; but in 4 patients, ORN was not diagnosed until after the time of infection and imaging. An early imaging finding of ORN was lingual cortical defects near the last molar. Pain followed by erythema, purulent drainage, and subperiosteal abscess by imaging were the most common signs of infection. In most patients, conservative management eventually failed and segmental mandibulectomies were required. CONCLUSIONS: Soft tissue infection with characteristic bone findings such as subperiosteal abscess and cortical bone erosions helps to distinguish infected ORN from recurrent tumor or sterile ORN. In patients previously treated with radiation who present with infection, pain or an avid PET scan with bone involvement, the mandible should be scrutinized.