Staphylococcus Aureus Infections Research Articles

Central venous catheter-related bloodstream infections: Epidemiology and risk factors for hematogenous complications

BackgroundCentral catheter-related bloodstream infections (CRBIs) can lead to severe complications, including suppurative thrombophlebitis, endocarditis, and metastatic infections. While complications due to CRBIs caused by Staphylococcus aureus (SA) are well-known, there are limited data regarding CRBIs caused by other bacteria. MethodsThis 2-year retrospective single-center study of patients with CRBIs from a tertiary care hospital examined the hematogenous complications associated with CRBIs according to patient characteristics, central venous catheter (CVC) types, and causative bacteria. ResultsAll in all, 254 patients with confirmed CRBIs were included; 285 bacteria types were isolated, mainly Enterobacteriaceae (n = 94), coagulase-negative Staphylococci (CNS, n = 82), SA (n = 45), and non-fermenting Gram-negative bacteria (NGB, n = 45). Among the patients, 35 developed at least one hematogenous complication (14 %), including suppurative thrombophlebitis (n = 15), endocarditis (n = 7) and metastatic infections (n = 16). In multivariate analysis, hemodialysis, persistent bacteremia for at least 3 days, and CRBIs caused by SA were associated with increased risk for hematogenous complications, while previous curative anticoagulant treatment was associated with reduced risk. Diabetes, CVC maintenance, and hematogenous complications were associated with increased 3-month mortality. ConclusionA thorough investigation of hematogenous complications should be envisioned in patients with persistent bacteremia, particularly those with SA infections and those on hemodialysis.

TREATMENT OF INTRACELLULAR S. AUREUS INFECTIONS IN OSTEOMYELITIS

Staphylococcus aureus (SA), the predominant pathogen in human osteomyelitis, is known to persist by forming intracellular reservoirs, including in bone cells (Schwarz et al., 2019, Yang et al., 2018, Krauss et al., 2019, Gao et al., 2020, Bosse et al., 2005), promoting decreased antibiotic susceptibility. However, there are no evidence-based treatment guidelines for intracellular SA infections in osteomyelitis. We sought to address this by systematically reviewing the literature and, testing a selection of antibiotic treatments in a clinically relevant in vitro assay.We conducted a systematic review of the literature to determine the current evidence for the efficacy of antibiotics against intracellular SA infections relevant to osteomyelitis. For the antibiotics identified as potentially useful, we determined their minimal inhibitory concentration (MIC) against 11 clinical osteomyelitis SA- isolates. We selected those for further testing reported able to reach a higher concentration in the bone than the identified MIC against the majority of strains. Thus, rifampicin, oxacillin, linezolid, levofloxacin, oritavancin and doxycycline were tested in human SaOS-2-osteocyte infection models (Gunn et al., 2021) of acute (1d) or chronic (14d) infection to clear intracellular SA. Antibiotics were tested at 1x/4x/10x the MIC for the duration of 1d or 7d in each model.A systematic review found that osteoblasts and macrophages have mostly been used to test immediate short-term activity against intracellular SA, with a high variability in methodology. However, some extant evidence supports that rifampicin, oritravancin, linezolid, moxifloxacin and oxacillin may be effective intracellular treatments. While studies are ongoing, in vitro testing in a clinically relevant model suggests that rifampicin, oxacillin and doxycycline could be effectively used to treat osteomyelitic intracellular SA infections. Importantly, these have lower MICs against multiple clinical isolates than their respective clinically-achievable bone concentrations.The combined approach of a systematic review and disease-relevant in vitro screening will potentially inform as to the best approach for treating osteomyelitis where intracellular SA infection is confirmed or suspected.

#68 Prevalence of Staphylococcus aureus bacteremia at Saint Damien Hospital, Nos Petits Frères et Sœurs January 2020-June 2021, Haiti

Abstract Background Nosocomial bacteremia is a healthcare-associated infection. It presents significant morbidity and mortality. Its prevention is based on the control of the risk factors, collection, and analysis of data to set up actions and measures aimed at educating staff, patients, and families to mitigate complications. Bacteremia is regularly monitored at Saint Damien Hospital (HSD);an increase in Staphylococcus aureus (SA) bacteremia was observed in January 2020. All SA infections were reviewed at St Damien during eighteen months to determine the prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) and the distribution by unit. Also, the frequency of nosocomial and community SA was determined. Nosocomial infections and those associated with SA remain a public health concern because of the antimicrobial resistance, the death rate, and the associated cost. Method A descriptive retrospective study was carried out over a period from January 2020 to June 2021 for all patients hospitalized in pediatrics who underwent a blood culture and whose results reported SA. Data were collected from microbiology laboratory registers and patient records. Results From January 2020 to June 2021, two thousand two hundred thirty-five (n = 2235) blood cultures were performed for a total of four thousand two hundred eighty-seven (n=4287) admissions. From these blood cultures performed, 11% of microorganisms (n=479) were isolated, of which 18.37% are SA (n=88). From these SA 68% were resistant to methicillin/MRSA (n=60), 32% sensitive to methicillin/MSSA (n=28).51% (n= 45) were associated with nosocomial infections (NI), 49% (n= 43) related to community infections. From the MRSA strains, 57% (n=34) are of nosocomial (NI) and 43% (n=26) are of community infection. These strains mainly came from emergency services 40% (n=24) followed by neonatology 22% (13) and intensive care 17% (10 ). The mortality rate for MRSA and MSSA were 32% (n=19) and 18% (n=5), respectively. 40% of MRSA isolates were multi-drug resistant (n=24). The resistance rate was 76% for penicillin (n=67) 65% for oxacillin (n=57) 35% for cefoxitin (n=31). Conclusion The frequency of isolation of Staphylococcus Aureus (SA) as well as the prevalence of SA and MRSA infections, was relatively high during this period. Its existence in a community setting and multidrug resistance to antibiotics is an alert making this bacteremia a public health priority to be monitored and brought under control.

#77 Prevalence of Staphylococcus aureus bacteremia at Saint Damien Hospital, Nos Petits Frères et Sœurs January (HSD/NPFS) 2020-June 2021, Haiti

Abstract Background Staphylococcus Aureus (SA) is one of the main agents implicated in healthcare-associated infections (HAI) [1]. These infections are associated with significant morbidity and mortality, particularly methicillin-resistant staphylococcal (MRSA) infections, and their costs are also a concern. Bacteremia is regularly monitored at Saint Damien Hospital (HSD), for the year 2020 an increase in Staphylococcus aureus (SA) bacteremia was observed in certain units of the hospital. In this context, all SA infections were reviewed during eighteen months to determine the prevalence of methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) staphylococcus aureus infections, their origins: in healthcare-associated infections (HAI), community-acquired infections (CI) and the distribution of MRSA per unit Method A Descriptive retrospective study was carried out at Saint Damien Hospital from January 2020 to June 2021. It includes all hospitalized children under fourteen years old (14) who had a positive blood culture for SA per site, only the 1st blood culture was taken into account. According to NHSN/CDC, are defined as infections associated with healthcare-associated infections occurring at ≥ 72 hours of hospitalization (HAI) and as community-acquired infectious infections occurring at = < 48 hours of hospitalization.. Data were collected from microbiology laboratory registers and patient records Results From January 2020 to June 2021, two thousand two hundred thirty five 2235 blood cultures were performed. The positivity rate was 21.43% (n=479/2235) distributed in different units. 16.49% SA strains were isolated (n=79/479), including fifty (50) strains of MRSA (63.29%) and twenty nine (29) strains of MSSA (36.70%) (n=29/79).From the strains of MRSA, 54% (n=27/50) were HAI and 46% community infections (CI) (n=23/50). The Origin of the infections (HAI/CI) was not significantly associated with MRSA and MSSA strains (p=0.6235), MRSA mainly came from emergency 48% (n=24/50) followed by neonatology 20% (n=10/50), intensive care 10% (5/50) and oncology at 10% (5/50). (n=19/79), the mortality rate attributable to MRSA and MSSA was 28% (n=14/50) and 17.24% (n=5/29), respectively. 46% of MRSA were resistant to more than 3 families of antibiotics (n = 23/50). SA strains were resistant to gentamycin at 30.37% (n=24/79) to 54.34% to sulfametoxazole (n=43/79) and 18.98% and to vancomycin (n=15/79 Conclusion The frequency of SA infections, specifically MRSA, is of great concern. Its existence in the community and its multiresistance, in particular to vancomycin, is an alert making this bacteremia a priority at Saint Damien Hospital, the standard precautions measures, the proper use of antibiotics by clinicians and epidemiological surveillance local would be needed to help control its spread.

Reducing Staphylococcus aureus infections in the neonatal intensive care unit.

Our neonatal intensive care unit (NICU) saw an increase in Staphylococcus aureus (SA) infections-methicillin-resistant SA (MRSA) infections increased from 2.1/10,000 patient days (PD) to 5.1/10,000 PD, and methicillin-sensitive SA (MSSA) infections from 1.2/10,000 PD to 3.9/10,000 PD. This quality improvement project aimed to decrease the rates of SA infections to less than 2.0/10,000 PD, and to determine the rate of SA decolonization. Infection prevention interventions targeted patient factors (SA surveillance, patient cohorting, decolonization protocol), provider factors (provider cohorting, enhanced hand hygiene) and environmental factors (room structure, equipment optimization). The rates of MRSA and MSSA infections decreased to 0.6/10,000 PD and 0.7 infections/10,000 PD respectively. Persistent decolonization of SA was successful in 67% of colonized patients. Specific interventions targeting patient, provider, and environmental factors, including the implementation of a SA decolonization protocol, were successful in decreasing the incidence of SA infections in neonates.

Protocolo para el manejo de las infecciones graves por Staphylococcus aureus

Staphylococcus aureus (SA) infections are common and have a high morbidity and mortality. The main antibiotics for treating methicillin-sensitive SA (MSSA) are cloxacillin and cefazolin. The main drugs for treating methicillin-resistant SA (MRSA) are vancomycin and daptomycin. Other antibiotics that may be of use include linezolid, rifampicin, or fluoroquinolones. In the empirical treatment of SA infections, the risk of MRSA must be taken into account. The treatment target and its duration, in absence of bacteremia, is conditioned in large part by the source of the infection and whether it is suitably controlled or not. When bacteremia is present, the possibility of infectious endocarditis must be evaluated and follow-up blood cultures must be conducted until they are negative. For uncomplicated bacteremia, 14 days of treatment from the first negative blood culture are necessary whereas if the bacteremia is complicated, treatment must have a duration of at least 28 days.

Adaptive Metabolism of Staphylococcus aureus Revealed by Untargeted Metabolomics.

Staphylococcus aureus (SA) is an opportunistic pathogen that can cause a wide spectrum of infections, from superficial skin inflammation to severe and potentially fatal and invasive diseases. Due to the many potential routes of infection, host-derived environmental signals (oxygen availability, nutrients, etc.) are vital for host colonization and thus contribute to SA's pathogenesis. To uncover the direct effects of environmental factors on SA metabolism, we performed a series of experiments in diverse culture environments and correlated our findings of SA's metabolic adaptation to some of the pathogen's known virulence factors. Untargeted metabolomics was conducted on a Thermo Q-Exactive high-resolution mass spectrometer. We detected 260 intracellular polar metabolites from our bacteria cultured under both aerobic and anaerobic conditions and in glucose- and dextrin-supplemented cultures. These metabolites were mapped to relevant metabolic pathways to elucidate the adaptive metabolic processes of both methicillin-sensitive SA (MSSA) and methicillin-resistant SA (MRSA). We also detected an increased expression of virulence genes agr-I and sea of MRSA supplemented with both glucose and dextrin by qPCR. With the metabolic data collected that may be associated with the adaptive growth and virulence of SA, our study could set up the foundations for future work to identify metabolic inhibitors/modulators to mitigate SA infections in different growth environments.

How we deal with Staphylococcus aureus (MSSA, MRSA) central nervous system infections.

Among central nervous system (CNS) infections (e.g., meningitis, brain abscess, ventriculitis, transverse myelitis), those caused by Staphylococcus aureus (SA) are particularly challenging both in management and treatment, with poor clinical outcomes and long hospital stay. It has been estimated that SA is responsible for around 1%-7% of meningitis (up to 19% in healthcare-associated meningitis). Recent neurosurgical procedures and immunocompromisation are major risk factors for SA CNS infections. Hand hygiene, surveillance nasal swabs and perioperative prophylaxis are crucial points for effective SA infections prevention. In case of SA-CNS infections, pending microbiological results, anti-methicillin-resistant SA (MRSA) antibiotic, with good CNS penetration, should be included, with prompt de-escalation as soon as MRSA is ruled out. Consultation with an expert in antimicrobial therapy is recommended as well as prompt source control when feasible. In this narrative review, we reviewed current literature to provide practical suggestions on diagnosis, prevention, management, and treatment of SA CNS infections.

Abstract 10302: A Case for Ending Rifampicin Use in Endocarditis

Background: Rifampicin has been employed in various endocarditis antibiotic regimens, particularly in prosthetic, staphylococcus aureus (SA) and culture-negative cases. However, this practice is not without controversy. Purpose: To perform a meta-analysis aimed at ascertaining the efficacy and safety of adjunctive rifampicin use in endocarditis. Methods: We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar, from inception to June 1st, 2021, for studies comparing rifampicin-containing antibiotic regimens with those comprising no rifamycin derivatives, in the setting of endocarditis. The primary endpoint was all-cause death, while relapse, bail-out valvular surgery, microbiological failure (lasting positivity of blood cultures) and hepatotoxicity (fivefold or higher increase in transaminase levels) were secondary outcomes. SA infections were investigated separately, with respect to the primary endpoint. Mantel-Haenszel odds ratios (ORs) were pooled using traditional meta-analytic techniques, under a random-effects model. Results: 2 randomized, 1 non-randomized prospective and 6 retrospective studies, featuring 886 patients (of whom 322 allocated to rifampicin), were included. While 8 studies addressed staphylococcal endocarditis (with 3 of them dealing exclusively with SA infections), prosthetic and culture-negative cases were only focused on 1 study each. There were 96 deaths (from 7 studies), 32 relapses (from 6 studies), 35 bail-out valvular surgeries (from 4 studies), 14 microbiological failures (from 2 studies) and 32 hepatotoxicity cases (from 5 studies). Rifampicin use was associated with a tendency towards higher all-cause mortality (OR 1.63, 95% CI 0.85-3.12, P 0.14, i 2 12%), which held true for SA infections (OR 1.63, 95% CI 0.67-3.92, P 0.28, i 2 20%), and bail-out valve surgery (OR 2.03, 95% CI 0.65-6.34, P 0.22, i 2 5%). Relapse and microbiological failures rates were similar between groups (OR 1.25, 95% CI 0.59-2.65, P 0.56, i 2 0% and OR 1.3, 95% CI 0.24-6.90, P 0.76, i 2 41%, respectively). Hepatotoxicity odds were greater in the rifampicin arm (OR 3.24, 95% CI 1.35-7.77, P 0.008, i 2 0%). Conclusion: Currently available evidence does not support rifampicin use in endocarditis.

Development of stable co‐culture of P. aeruginosa and S. aureus in Artificial Sputum Medium

Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) are both opportunistic pathogens that are known to cause severe respiratory infections in humans. While these pathogens don't commonly cause infections in healthy individuals, they are often found in patients with chronic lung diseases, such as Cystic Fibrosis (CF). Data from people with CF disease indicates that CF lungs are predominantly infected with SA at a younger age with PA appearing later (<10 years) when it then outcompetes SA. There is, however, significant overlap where both pathogens co-exist in the patient's lungs. While clinical data on prevalence is abundant, little data exists on mechanisms of competition of two pathogens in CF lungs. Artificial sputum medium (ASM) is a culture medium that was designed to mimic sputum from CF patients. It contains components of CF sputum, such as amino acids, mucin and DNA. It was shown that PA growth in the ASM is similar to the growth in the lungs of CF patients. We hypothesised that the ASM model could be adapted to study the interaction between SA and PA in a controlled environment that is relevant to the in vivo environment of CF lungs. SA (ATCC29213) and PA (H174) were grown in the artificial sputum media (ASM). Approximately 3x105 bacteria were added to 15 mL ASM and grown at 37oC with constant shaking. Conditioned media was prepared by growing SA in ASM for 24 hours and then removing SA. SA appeared to adapt quicker to the nutrient-poor environment of ASM than PA and enters logarithmic growth immediately upon incubation, as opposed to PA, which exhibited an 8-hour lag period. When both pathogens are added simultaneously to the ASM, SA outcompeted PA and dominated the culture restricting the growth of PA. To better mimic in vivo conditions, ASM was conditioned by adding SA for 24 hours. This allowed creation of an environment that is similar to that found in the CF lungs with established SA infections. When both pathogens were added into the conditioned media, PA did not exhibit the lag phase and outcompeted SA, suppressing its growth. This effect remained even if SA outnumbered PA 10 000-fold. In an attempt to create media that is most similar to that of CF sputum, ASM was mixed 50:50 with conditioned media, which represents the constant renewal of secreted products and nutrients seen in the lungs. When both pathogens were added to the media, rapid growth was observed in both pathogens for 24 hours. After 24 hours the population of SA decreased from 1x109 CFU/ml to 3x106 CFU/ml, while the PA population remained stable at 1x108 CFU/ml. After 48 hours, the population of both pathogens remained constant. By modifying ASM with conditioned ASM, we have created a stable in vitro co-culture of Staphylococcus aureus and Pseudomonas aeruginosa. Our model can be utilised to examine the competition and/or co-existence between clinical strains and other bacterial species that reside within the lungs and identify factors which suppress pathogen growth.

1349. Institutional Antibiograms Are Insufficient to Guide Clindamycin Use in Pediatric Skin and Soft Tissue Infections

BackgroundClindamycin (CLN) is a common empiric antimicrobial for pediatric skin and soft tissue infections (SSTI) despite decreasing susceptibility of Staphylococcus aureus (SA) to CLN on institutional antibiograms. This study inquired whether institutional antibiograms are an accurate representation of susceptibility for these infections. It also attempted to find patient and infection characteristics associated with being clindamycin susceptible (CLN-S).MethodsThis was a retrospective chart review of children with community-acquired (CA) SA infections in 2016 and 2017. A Staphylococcus aureus antibiogram was created based on infection type. Various patient and infection characteristics were compared between CLN-S and clindamycin-resistant (CLN-R) isolates to identify predictors of being CLN-S via binary logistic regression. Characteristics with p < 0.2 from a univariate analysis (chi-square or Fisher’s exact test) were included in the regression; p < 0.05 after the regression was considered statistically significant.Results362 SA infections were included. These were 76% CLN-S, similar to the institutional antibiogram (79% CLN-S, p = 0.168). MSSA CLN susceptibility was lower than the antibiogram (71% vs. 79% CLN-S, p = 0.042). MRSA susceptibility was similar (79% vs. 80% CLN-S, p = 0.859). Infection types assessed were abscess (n = 264, 81% CLN-S), osteomyelitis (n = 40, 75% CLN-S), lymph node (n = 16, 75% CLN-S), staphylococcal scalded skin syndrome (n = 9, 56% CLN-S), eczema superinfection (n = 17, 53% CLN-S), bullous impetigo (n = 7, 40% CLN-S), and non-bullous impetigo (n = 7, 29%). Characteristics found to be associated with being CLN-S included abscess (OR 3.883, p = 0) and high white blood cell count (OR 2.482, p = 0.001). Characteristics associated with CLN-R included contact to person with abscess (OR 0.468, p = 0.035) and hypotension during infection (OR 0.312, p = 0.005).ConclusionThe use of institutional antibiograms to guide CLN susceptibility in CA SA infections may be limited by the type of infection, patient characteristics, and the likelihood of MSSA vs. MRSA infection. In our patients, having an abscess was associated with CLN-S. Empiric therapy of CA SA infections in children should not be driven solely by institutional antibiograms.Disclosures All Authors: No reported disclosures

IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcusaureus

Allergies are considered to represent mal-directed type 2 immune responses against mostly innocuous exogenous compounds. Immunoglobulin E (IgE) antibodies are a characteristic feature of allergies and mediate hypersensitivity against allergens through activation of effector cells, particularly mast cells (MCs). Although the physiological functions of this dangerous branch of immunity have remained enigmatic, recent evidence shows that allergic immune reactions can help to protect against the toxicity of venoms. Because bacteria are a potent alternative source of toxins, we assessed the possible role of allergy-like type 2 immunity in antibacterial host defense. We discovered that the adaptive immune response against Staphylococcus aureus (SA) skin infection substantially improved systemic host defense against secondary SA infections in mice. Moreover, this acquired protection depended on IgE effector mechanisms and MCs. Importantly, our results reveal a previously unknown physiological function of allergic immune responses, IgE antibodies, and MCs in host defense against a pathogenic bacterium.

The effect of routine surveillance and decolonization on the rate of Staphylococcus aureus infections in a level IV neonatal intensive care unit.

To evaluate the impact of active surveillance cultures (ASC) for Staphylococcus aureus (SA) and decolonization on the rate of infection in neonates in a neonatal intensive care unit (NICU). Using a quasi-experimental design with control groups, rates of SA infections before and after implementing weekly ASC and topical mupirocin decolonization in a level IV NICU were compared. Comparators were the rates of gram negative bloodstream infections (BSI) and of SA BSI at an affiliated NICU where the intervention was not implemented. There was a 77% (p < 0.010) reduction in rate of NICU-wide methicillin-susceptible SA (MSSA) BSI, but no significant change in rate of methicillin-resistant SA BSI, likely due to a prevalent mupirocin-resistant clone. Rates of gram negative BSI and SA BSI at an affiliated NICU did not change significantly. Weekly ASC and decolonization were associated with a unit-wide reduction in MSSA infections in a NICU.

Assessment of invitrosynergy of daptomycin or vancomycin plus ceftaroline for daptomycin non-susceptible Staphylococcus aureus

The combination of vancomycin or daptomycin plus ceftaroline has showed synergistic results in vitro. This study aimed to investigate in vitro synergy of vancomycin or daptomycin plus ceftaroline for seven patients with daptomycin non-susceptible Staphylococcus aureus (SA) bacteremiaThirteen isolates from seven patients were evaluated: two methicillin-susceptible and five methicillin-resistant SA infections. All patients were treated with daptomycin and became non-susceptible (minimum inhibitory concentration (MIC) >1 μg/mL) with therapy or had resistant strains initially. Time kill experiments were completed with 0.25 × MIC, 0.5 × MIC, and 0.75 × MIC concentrations. No synergy was seen at 0.25 × MIC. Synergy was observed for 4 isolates with vancomycin plus ceftaroline and with daptomycin plus ceftaroline for 2 isolates at 0.5 × MIC.These results are in accordance with literature that supports synergistic combinations of daptomycin or vancomycin with ceftaroline for SA bacteremia. Daptomycin non-susceptible SA bacteremia presents a treatment challenge.

Methicillin-Resistant Staphylococcus aureus: Risk for General Infection and Endocarditis Among Athletes.

The first studies on Staphylococcus aureus (SA) infections in athletes were conducted in the 1980s, and examined athletes that perform in close physical contact, with particular attention to damaged or infected skin. Recent studies have used molecular epidemiology to shed light on the transmission of SA in professional athletes. These studies have shown that contact between athletes is prolonged and constant, and that these factors influence the appearance of infections caused by SA. These results support the need to use sanitary measures designed to prevent the appearance of SA infections. The factors triggering the establishment of SA within professional sports groups are the nasal colonization of SA, contact between athletes and sweating. Hence, there is a need to use the most modern molecular typing methods to evaluate the appearance of cutaneous SA disease. This review aims to summarize both the current SA infections known in athletes and the diagnostic methods employed for recognition, pointing to possible preventive strategies and the factors that can act as a springboard for the appearance of SA and subsequent transmission between athletes.

Burden of Staphylococcus aureus infections after orthopedic surgery in Germany

BackgroundThis study assessed incidence, risk factors, and outcomes of Staphylococcus aureus infections (SAI) following endoprosthetic hip or knee, or spine surgeries.MethodsAdult patients with at least one of the selected surgeries from 2012 to 2015 captured in a German sickness fund database were included. SAI were identified using S. aureus-specific ICD-10 codes. Patients with certain prior surgeries and infections were excluded. Cumulative incidence and incidence density of post-surgical SAI were assessed. Risk factors, mortality, healthcare resource utilization and direct costs were compared between SAI and non-SAI groups using multivariable analyses over the 1 year follow-up.ResultsOverall, 74,327 patients who underwent a knee (28.6%), hip (39.6%), or spine surgery (31.8%) were included. The majority were female (61.58%), with a mean age of 69.59 years and a mean Charlson Comorbidity Index (CCI) of 2.3. Overall, 1.92% of observed patients (20.20 SAI per 1000 person-years (PY)) experienced a SAI within 1 year of index hospitalization. Knee surgeries were associated with lower SAI risk compared with hip surgeries (Hazard Ratio (HR) = 0.8; p = 0.024), whereas spine surgeries did not differ significantly from hip surgeries. Compared with non-SAI group, the SAI group had on average 4.4 times the number of hospitalizations (3.1 vs. 0.7) and 7.7 times the number of hospital days (53.5 vs. 6.9) excluding the index hospitalization (p < 0.001). One year post-orthopedic mortality was 22.38% in the SAI and 5.31% in the non-SAI group (p < 0.001). The total medical costs were significantly higher in the SAI group compared to non-SAI group (42,834€ vs. 13,781€; p < 0.001). Adjusting for confounders, the SAI group had nearly 2 times the all-cause direct healthcare costs (exp(b) = 1.9; p < 0.001); and 1.72 times higher risk of death (HR = 1.72; p < 0.001).ConclusionsSAI risk after orthopedic surgeries persists and is associated with significant economic burden and risk of mortality. Hence, risk reduction and prevention methods are of utmost importance.

Epidemiology, Drug Resistance, and Virulence of Staphylococcus aureus Isolated from Ocular Infections in Polish Patients.

Analysis of the epidemiology of Staphylococcus aureus (SA) ocular infections and virulence factors of the isolates with a special emphasis on their drug resistance, and the ability of biofilm formation. In a period from 2009 to 2013, 83 isolates of SA were prospectively collected and preserved in a multicenter laboratory-based study carried out in southern Poland. Epidemiological, phenotypic, and genotypic analyses were performed. The resistance and virulence genes were analyzed. Screening for the biofilm formation was provided. Among the materials derived from ocular infections from 456 patients, SA was found in 18.2% (n = 83) of cases (one SA isolate per one patient). Most infections were identified in the age group of over 65 years (OR 8.4 95%CI; 1.03-68.49). The majority of patients (73.4%) were hospitalized. Among the virulence and resistance genes, the most frequently detected were the lukE (72.2%, n = 60) and ermA (15.6%, n = 13) genes. A positive result of the CRA test (the ability of biofilm formation) was found in 66.2% (n = 55) of isolates. Among the strains under study, 6.0% (n = 5) had the methicillin-resistant Staphylococcus aureus phenotype, and 26.5% (n = 22) had the macrolide-lincosamide-streptogramin B phenotype. In 48 (57.8%) isolates the neomycin resistance was revealed. All isolates under study were sensitive to vancomycin. The population most susceptible to ocular SA infections consists of hospitalized patients aged 65 and more. The SA strains under study showed the increased ability to biofilm formation. In the strains tested, high susceptibility to chloramphenicol and fluoroquinolones was demonstrated. However, the high level of drug resistance to neomycin detected in this study among SA isolates and the blood-ocular barrier makes it difficult to treat ocular infections.

Risk factors for the appearance of secondary foci of infection in children with community-acquired Staphylococcus aureus bacteraemia. Cohort study 2010–2016

IntroductionCommunity-acquired Staphylococcus aureus (SA) bacteraemia is a common cause of hospitalisation in children. The occurrence of secondary foci (SF) of SA infection is associated with higher morbidity and mortality. ObjectivesTo identify risk factors for SF of infection in children with community-acquired SA bacteraemia. Material and methodsProspective cohort. All children aged from 30 days to 16 years admitted to a paediatric referral hospital between January 2010 and December 2016 for community-acquired infections, with SA isolated in blood cultures, were included. Microbiological, demographic and clinical characteristics were compared, with or without SF infection after 72h of hospitalisation. ResultsA total of 283 patients were included, 65% male (n=184), with a median age of 60 months (IQR: 30–132). Seventeen per cent (n=48) had at least one underlying disease and 97% (n=275) had some clinical focus of infection, the most common being: osteoarticular 55% (n=156) and soft tissue abscesses 27% (n=79). A total of 65% (n=185) were resistant to methicillin. A SF of infection was found in 16% of patients (n=44). The SF identified were pneumonia 73% (n=32), osteoarticular 11% (n=5), soft tissue 11% (n=5) and central nervous system 5% (n=2). In the multivariate analysis, the persistence of positive blood cultures after the fifth day (OR: 2.40, 95%CI: 1.07–5.37, p<0.001) and sepsis (OR: 17.23, 95%CI 5.21–56.9, p<0.001) were predictors of SF. There was no association with methicillin sensitivity. ConclusionsIn this cohort, methicillin-resistant SA infections predominated. The occurrence of SF of infection was associated with the persistence of bacteraemia after the fifth day and sepsis on admission.

Alpha-Toxin Contributes to Biofilm Formation among Staphylococcus aureus Wound Isolates.

Biofilms complicate treatment of Staphylococcus aureus (SA) wound infections. Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and biofilm formation on epithelium and assessed the role of AT in biofilm formation. Thirty-eight wound isolates were molecularly typed by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (ST), and spa typing. We measured biofilm formation of these SA isolates in vitro and ex vivo and quantified ex vivo AT production. We also investigated the effect of an anti-AT monoclonal antibody (MEDI4893*) on ex vivo biofilm formation by methicillin-resistant SA (USA 300 LAC) and tested whether purified AT rescued the biofilm defect of hla mutant SA strains. The predominant PFGE/ST combinations were USA100/ST5 (50%) and USA300/ST8 (33%) for methicillin-resistant SA (MRSA, n = 18), and USA200/ST30 (20%) for methicillin-susceptible SA (MSSA, n = 20). Ex vivo AT production correlated significantly with ex vivo SA wound isolate biofilm formation. Anti-alpha-toxin monoclonal antibody (MEDI4893*) prevented ex vivo biofilm formation by MRSA USA300 strain LAC. Wild-type AT rescued the ex vivo biofilm defect of non-AT producing SA strains. These findings provide evidence that AT plays a role in SA biofilm formation on epithelial surfaces and suggest that neutralization of AT may be useful in preventing and treating SA infections.

Methicillin resistance in Staphylococcus aureus infections among patients colonized with methicillin-susceptible Staphylococcus aureus

ObjectivesWe have noticed that patients colonized with methicillin-susceptible Staphylococcus aureus (MSSA) rarely get methicillin-resistant S. aureus (MRSA) infections. The purpose of this study was to compare the odds of a Staphylococcus aureus (SA) infection being an MRSA infection in MSSA carriers, MRSA carriers and non-carriers of SA. MethodsHospitalizations of adult patients at the Cleveland Clinic Health System from 2008 to 2015 were screened to identify those where the patient was tested for SA colonization. The first such hospitalization was identified. Among these 90 891 patients, those who had an SA infection during the hospitalization were included. SA carrier status (MRSA, MSSA, or non-carrier), was defined based on the first nasal SA test result. The association of carrier status and MRSA infection was examined. ResultsThe mean (±standard deviation (SD)) age of the 1999 included patients was 61 (17) years, and 1160 (58%) were male. Thirty percent, 26%, and 44%, were MRSA carriers, MSSA carriers and non-carriers, respectively. Of the 601 SA infections in MRSA carriers (reference group), 552 (92%) were MRSA infections compared with 42 (8%) of 516 in MSSA carriers (odds ratio (OR) 0.008, 95% confidence interval (CI) 0.005–0.012, p <0.0001) and 430 (49%) of 882 in non-carriers (OR 0.072, 95% CI 0.051–0.100, p <0.0001), after controlling for age, sex, hospital length of stay and calendar year. ConclusionAmong patients with SA infection, the odds of the infection being an MRSA infection are 125-times lower in an MSSA carrier than in an MRSA carrier.