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Abstract Staphylococci are the main pathogens associated with hard-to-control intramammary infections in dairy cattle, and bacterial biofilms are suspected to be responsible for the antimicrobial resistance and persistence of this disease. Biofilms have the ability to resist to higher levels of antibiotics and reduce their efficacy. It is thus necessary to develop strategies targeted to bacterial biofilm infections. Chitosan is a polysaccharide with a proven broad spectrum of antimicrobial activity against fungi and bacteria. The aim of this study was assess the effect of low molecular weight (LMW) chitosan against biofilm hyperproducer Staphylococcus spp. (S. aureus and S. xylosus) strains usually involved in chronic bovine mastitis, and to test their efficacy in biofilm formation and eradication. The results obtained showed that LMW chitosan is able to inhibit S. aureus and S. xylosus planktonic growth in a dose-dependent manner and reduce bacterial viability. LMW chitosan inhibits biofilm formation, reduces biofilm viability and disrupts established biofilm. These results indicate the inhibitory effects of chitosan on biofilm formation, and these effects are observed at lower concentrations for S. xylosus. Our studies show the potential of this biopolymer to be used as an effective antibiofilm agent able to act upon staphylococcal infections. Highlights • LMW chitosan inhibits staphylococci planktonic growth in a dose-dependent manner. • The antibacterial activity of chitosan was higher against S. xylosus than S. aureus. • LMW chitosan inhibits staphylococci biofilm formation and disrupt biofilm structure. • LMW chitosan decreases the viability of planktonic and biofilm bacteria. • LMW chitosan could be an effective anti-biofilm strategy for mastitis treatment. [ABSTRACT FROM AUTHOR]

Background: Postneurosurgical ventriculitis is mainly caused by coagulase-negative staphylococci. The rate of linezolid-resistant Staphylococcus epidermidis (LRSE) is increasing worldwide.Aims: To report clinical, epidemiological and microbiological data from a series of ventriculitis cases caused by LRSE in a Spanish hospital between 2013 and 2016.Methods: Cases of LRSE ventriculitis were reviewed retrospectively in a Spanish hospital over a four-year period. Clinical/epidemiological data of the infected patients were reviewed, the isolates involved were typed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing, and the molecular bases of linezolid resistance were determined.Findings: Five cases of LRSE ventriculitis were detected. The patients suffered from cerebral haemorrhage or head trauma that required the placement of an external ventricular drain; spent a relatively long time in the intensive care unit (ICU) (10-26 days); and three out of the five patients had previously been treated with linezolid. All LRSE had the same PFGE pattern, belonged to ST2, and shared an identical mechanism of linezolid resistance. Specifically, all had the G2576T mutation in the V domain of each of the six copies of the 23S rRNA gene, together with the Q136L and M156T mutations and the 71GGR72 insertion in the L3 and L4 ribosomal proteins, respectively.Conclusion: The high ratio of linezolid consumption in the ICU (7.72-8.10 defined daily dose/100 patient-days) could have selected this resistant clone, which has probably become endemic in the ICU where it could have colonized admitted patients. Infection control and antimicrobial stewardship interventions are essential to prevent the dissemination of this difficult-to-treat pathogen, and to preserve the therapeutic efficacy of linezolid. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that the ideal therapeutic effect of linezolid cannot be achieved in critically ill patients with the recommended standard dosing regimen of 600 mg every 12 h (q12h). Moreover, the optimal strategy for successful treatment is still lacking. This study analysed factors influencing the efficacy of linezolid treatment and determined the target for successful treatment by logistic regression in 27 critically ill patients with staphylococcal infection who received linezolid 600 mg q12h. The results showed that only the 24-h area under the concentration–time curve to minimum inhibitory concentration (AUC 24 /MIC) ratio was significantly associated with staphylococcal eradication. Reaching 80% bacterial eradication required an AUC 24 /MIC of 120.5, defining the therapeutic target. Different dosing regimens were evaluated using Monte Carlo simulation to determine the optimal dosage strategy for linezolid. Although the probability of target attainment (PTA) was high (>99.9%) for the standard dosing regimen at MIC ≤ 1 mg/L, the PTA was almost 0 at MIC = 2 mg/L, thus the dosing regimen required adjustment. In addition, if the dosing regimen was adjusted to 600 mg every 8 h or 600 mg every 6 h, the major staphylococci (except for MRSA and MSSA) exhibited a cumulative fraction of response of >80%, showing a higher treatment success. These findings indicate that a strategy of high linezolid dosage may be needed to increase the probability of successful treatment at MIC > 1 mg/L. The role of therapeutic drug monitoring should be encouraged for optimising linezolid exposure in critically ill patients. [ABSTRACT FROM AUTHOR]

Summary Objectives Pharmacokinetics of clindamycin in combination with rifampicin or levofloxacin were prospectively evaluated for the oral treatment of severe staphylococcal osteo articular infections. Methods Thirty-four patients (25 males, 9 females), with a mean age of 52.4 ± 17 years (range, 24–81 years), were randomly assigned either to the clindamycin-rifampicin or to the clindamycin-levofloxacin arm (control), following surgical debridement and intravenous adapted treatment. Trough and peak serum concentrations of clindamycin were measured at day-1 (D1), D15 and D30 of oral treatment. Cure was evaluated at a minimum of one year after the initiation of treatment. Results The oral treatment was interrupted in 4 cases because of adverse events. Mean trough and peak serum concentrations of clindamycin in the clindamycin-rifampicin arm were lower than in the clindamycin-levofloxacin arm during the time of oral antibiotic regimen (0.79 ± 0.3 μg/ml vs 4.7 ± 1.2 μg/ml, p < 0.001, and 3.48 ± 1.1 μg/ml vs 10.2 ± 1.8 μg/ml, p < 0.001, respectively). A consistent decrease in clindamycin serum concentration was observed at each time-point of follow-up. At a mean of 23 ± 7.8 months (range, 12–47 months), 24 patients were available for clinical evaluation. No difference could be detected in the cure rates between the groups. Conclusions Our results indicate a significant influence of rifampicin on clindamycin pharmacokinetics using the oral route. Clindamycin serum concentrations (trough and peak) were systematically below the recommended therapeutic ranges when associated with rifampicin, as opposed to the control. Considering the potential risk of selection of mutant resistant to clindamycin, we do not recommend the clindamycin-rifampicin combination in the oral treatment of severe staphylococcal osteoarticular infection, unless clindamycin serum concentration is thoroughly controlled. The study has been registered on the clinicaltrials.gov website under the number NCT 01500837 . [ABSTRACT FROM AUTHOR]

The aim of this multicentre study was to analyse the characteristics of patients with bloodstream infections due to staphylococcal strains resistant to linezolid. This was a retrospective case–case–control study of patients hospitalised in three large teaching hospitals in Italy. A linezolid-resistant (LIN-R) Staphylococcus spp. group and a linezolid-susceptible (LIN-S) Staphylococcus spp. group were compared with control patients to determine the clinical features and factors associated with isolation of LIN-R strains. All LIN-R Staphylococcus spp. strains underwent molecular typing. Compared with the LIN-S group, central venous catheters were the main source of infection in the LIN-R group. The LIN-R and LIN-S groups showed a similar incidence of severe sepsis or septic shock, and both showed a higher incidence of these compared with the control group. Overall, patients in the LIN-R group had a higher 30-day mortality rate. Multivariate analysis found previous linezolid therapy, linezolid therapy >14 days, antibiotic therapy in the previous 30 days, antibiotic therapy >14 days, previous use of at least two antibiotics and hospitalisation in the previous 90 days as independent risk factors associated with isolation of a LIN-R strain. The G2576T mutation in domain V of 23S rRNA was the principal mechanism of resistance; only one strain of Staphylococcus epidermidis carried the cfr methylase gene (A2503), together with L4 insertion ( 71 GGR 72 ) and L3 substitution (H146Q). LIN-R strains are associated with severe impairment of clinical conditions and unfavourable patient outcomes. Reinforcement of infection control measures may have an important role in preventing these infections. [ABSTRACT FROM AUTHOR]

Background There are few studies on the histologic findings in native infective endocarditis, especially regarding mimics of autoimmune valvulitis. Methods We prospectively studied 106 surgical specimens from 95 patients with a clinical diagnosis of infective endocarditis on native valves, and compared gross and histologic findings with culture results, underlying valve disease, risk factors and time interval from symptom onset to surgical intervention. Results There were 41 (39%) aortic, 33 (31%) mitral, 9 (9%) tricuspid, 1(.9%) pulmonic and 11 (10%) multiple valve replacements. Underlying valve disease was present in 26 (27%) patients (non-calcified bicuspid aortic valve, 10 (38%) cases; mitral valve prolapse, 5 (19%) cases; calcified trileaflet aortic valve, 5 (19%) cases; calcified bicuspid aortic valve, 2 (8%) cases; post-rheumatic mitral valve disease, 2 (8%) cases; hypertrophic cardiomyopathy-related mitral valve disease, 1 (4%) case, trileaflet aortic insufficiency 1 (4%) case) and associated with streptococcal infection ( p = .001). Absence of underlying valve disease was associated with intravenous drug abuse ( p = .01) and dialysis dependent renal disease ( p = .006). Intravenous drug abuse was associated with staphylococcal infection ( p = .03). Vegetations were present in 80 (75%) of cases, and on the nonflow surface of the valve in 65 (81%) of these. Gram-stain positivity and neutrophilic microabscesses were associated with staphylococcal infection ( p = .03). Epithelioid macrophages with palisading features mimicking necrobiotic granulomas were seen in 42 (40%) valves and more frequently associated with streptococcal infection ( p = .03). As expected, the presence of valve necrosis and acute inflammation decreased with an increase in time with respect to symptomatic onset. Conclusion Histologic findings that mimic autoimmune inflammation are frequent in infective endocarditis and associated with streptococcal infection. Risk factors for infective endocarditis include calcific valve disease. [ABSTRACT FROM AUTHOR]

In recent years, the fight against nosocomial infections has constituted a major public health challenge. Measures aimed at preventing the spread of multiresistant bacteria (MRB) through carriage combine the more or less systematic detection of carriers and precautions concerning isolation. In the light of published data, elements for the evaluation of a cost-efficiency ratio for measures concerning detection and isolation in intensive care are presented. The high levels of methicillin-resistant Staphylococcus aureus (MRSA) observed in hospitals constitute the principal target. Although isolation precautions appear to be effective, the value of detecting MRSA remains a subject of debate. Such detection has several objectives: the identification of carriers, assistance in the implementation of isolation precautions, the eradication of carriage and the evaluation of strategy. These different objectives are discussed. [Copyright &y& Elsevier]