Staphylococcus Aureus Isolates Research Articles

1946. In Vitro Activity of Ceftobiprole against Staphylococcus aureus Bacteremia Isolates from the United States (2018–2020)

Abstract Background Ceftobiprole (BPR) is an advanced-generation cephalosporin approved in Europe and many non-European countries for the treatment of community-acquired pneumonia and non–ventilator-associated hospital-acquired pneumonia in adults. A Phase 3 clinical trial (NCT03138733) was recently completed with BPR for the treatment of Staphylococcus aureus (SA) bacteremia, including infective endocarditis. This study evaluated the activity of BPR and comparators against recent SA isolates causing bloodstream infections (BSI) in patients hospitalized at medical centers in the United States (US). Methods A total of 1,946 SA isolates from 32 US medical centers (2018–2020) were collected from patients with BSI. 53 isolates from endocarditis patients were included. Isolates were tested for antimicrobial susceptibility using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. MIC interpretations for BPR and comparators utilized European Committee on Antimicrobial Susceptibility Testing (EUCAST) or CLSI criteria, respectively. Multidrug-resistant (MDR) isolates were non-susceptible to ≥ 3 of the following drugs without regard to oxacillin resistance: clindamycin, daptomycin, erthryomycin, gentamicin, levofloxacin, tetracycline, and trimethoprim-sulfamethoxazole. No isolates were resistant to linezolid, tigecycline, or vancomycin. Results BPR inhibited 99.5% of all SA at ≤ 2 mg/L, which is the EUCAST susceptibility breakpoint (MIC50/90, 0.5/2 mg/L). The MIC50/90 values were stable over all 3 surveillance years and identical to previously reported values from analogous isolates collected in 2016–2017. BPR activity was maintained against the methicillin-resistant SA (MRSA) subset (41% of all SA; 98.8% susceptible). All isolates from endocarditis patients were susceptible to BPR. 10 MRSA isolates (0.5%) were resistant to BPR with MIC values of 4 mg/L. Of 288 MDR isolates, 96.9% remained susceptible to BPR, while only 78.8% of the same isolate set was susceptible to ceftaroline. Conclusion These in vitro results extend previous surveillance data that suggest that BPR represents a potential option for treating BSI and endocarditis caused by SA in US hospitals, including MRSA and MDR isolates. Disclosures Leonard R. Duncan, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds Mark E. Jones, PhD, Astellas Pharma Global Development, Inc: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support

Panton-Valentine leucocidin-producing Staphylococcus aureus: a clinical review.

Panton-Valentine leucocidin (PVL) is a virulence factor produced by certain strains of Staphylococcus aureus (SA). Through its cytolytic action on the cell membranes of human polymorphonuclear neutrophils, PVL causes a range of pathologies collectively known as PVL-SA disease. The hallmark clinical signs of PVL-SA are recurrent boils and necrotizing skin and soft tissue infections (SSTIs) in otherwise healthy patients; however, it can lead to more severe and invasive presentations, including necrotizing haemorrhagic pneumonia, necrotizing fasciitis and purpura fulminans. Young adults with minimal previous exposure to healthcare settings tend to be at highest risk for acquiring PVL-SA disease, with close physical contact playing a central role in disease transmission. The prevalence of PVL-SA varies globally; however, this is often underestimated owing to a lack of routine PVL testing. In the UK, PVL-positive SA isolates have been rising over the past decade alongside an increasing prevalence of multidrug resistance in larger cities. This review article aims to raise awareness of the PVL toxin, to aid clinicians with diagnostic pointers and to provide guidance with treatment, with an emphasis on the need for further population-based studies.

Mupirocin susceptibility of staphylococci 2022: Is it time for a change in MRSA decolonization protocols?

Nasal decolonization with mupirocin has been a common strategy for the prevention of surgical site infections (SSIs) and recurrent skin and soft tissue infections due to Staphylococcus aureus (SA). We recently noted an increase in SSIs due to SA, including a case of post-operative mupirocin-resistant methicillin-resistant SA (MRSA) infection despite attempted preoperative decolonization with mupirocin. We therefore evaluated the mupirocin susceptibility of SA at our hospital to determine the optimal regimen for decolonization. SA isolates were recovered from clinical and screening samples received in the microbiology laboratory. Mupirocin susceptibility was determined using e-tests and isolates were categorized as susceptible or resistant using a breakpoint MIC value of 4mcg/ml. 223 unique SA isolates from 218 patients were tested. Twenty-four SA isolates (10.8%) were resistant to mupirocin (20 MRSA and 4 methicillin-sensitive SA [MSSA]). MRSA strains were more likely to be resistant to mupirocin than MSSA strains (22.5% vs 3.0%, P < .001). The emergence of drug resistance makes the policy of decolonization with nasal mupirocin a suboptimal strategy for the prevention of MRSA infections. In our study, less than 80% of MRSA strains were mupirocin susceptible. In patients colonized with MRSA at high risk for infection (eg, total joint replacement), other regimens such as intranasal povidone iodine may be preferable to mupirocin for patient decolonization.

1059. In vitro Activity of Exebacase (CF-301) against Staphylococcus aureus Causing Bacteremia in the United States, Including Multidrug-resistant Subsets

1059. <i>In vitro</i> Activity of Exebacase (CF-301) against <i>Staphylococcus aureus</i> Causing Bacteremia in the United States, Including Multidrug-resistant Subsets

206. Clinical and Molecular Characteristics of Community-associated Staphylococcus aureus Bacteremia in Injection and Non-injection Drug Users at a New York City Medical Center

Abstract Background The opioid epidemic has resulted in a dramatic resurgence of bacterial infections, most notably those due to Staphylococcus aureus (SA). We compared the demographic, clinical, and molecular factors of injection drug users (IDUs) and non-IDUs with SA bacteremia. Methods Patients with SA bacteremia were identified through a query of the electronic medical record EMR from January 2018 to December 2019 at a New York City medical center. All cases of community-associated (CA) SA bacteremia among adults with a history of active injection drug use were evaluated. Patients with positive SA blood cultures ≤ 72 hours of admission were considered CA. IDUs were identified with keyword searches and were deemed active if they had a history of use in the 12 months prior to admission. A randomly selected group of non-IDUs with CA SA bacteremia was used for comparison at a 4:1 ratio. Available SA isolates underwent Illumina whole genome sequencing (WGS). Using SRST2 multilocus sequence types (MLST), antimicrobial resistance genes and putative virulence factors were extracted. Results From January 2018 to December 2019, 669 patients with SA bacteremia were identified. 29 patients were active IDUs. Compared to 112 randomly selected non-IDUs, IDUs were significantly younger and more likely to be unstably housed (Table 1). Rates of MRSA were similar in IDUs (31%) and non-IDUs (32.1%). Endocarditis (44.8% vs 11.6%) and abscesses (27.6% vs 8.9%) were diagnosed more frequently in IDUs than non-IDUs. A positive hepatitis C antibody was strongly associated with SA bacteremia in IDUs (62.1% vs 6.3%, p&amp;lt; 0.001). WGS demonstrated comparable proportions of sequence types across IDUs and non-IDUs. ST8 accounted for the majority of infections in both groups (Table 2). MRSA bacteremia due to ST8 occurred in a higher proportion of IDUs (7/29, 24.1%) than non-IDUs (14/112, 12.5%). Conclusion IDUs with CA SA bacteremia have unique demographic and clinical features that differentiate them from non-IDUs. Endocarditis rates in IDUs are of particular concern. Use of these risk factors could allow hospitals to rapidly identify IDUs and offer them necessary medical and social services. WGS revealed a majority of MRSA bacteremia was due to one sequence type in IDUs (ST8). Further analysis of virulence genes in this cohort are ongoing. Disclosures Franklin D. Lowy, MD, GlaxoSmithKline (Advisor or Review Panel member)UpToDate (Other Financial or Material Support, Topic Writer and Editor) Anne-Catrin Uhlemann, MD, PhD, Merck (Grant/Research Support)

High Prevalence of Methicillin-Resistant Staphylococcus aureus among Healthcare Facilities and Its Related Factors in Myanmar (2018-2019).

Background: Antimicrobial resistance (AMR) is a growing global health problem. Staphylococcus aureus (SA) is a common bacterium associated with a variety of community and hospital infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounts for most SA related morbidity and mortality. In this study, we determined the prevalence and factors associated with SA and MRSA in Myanmar. Methods: We collected the data retrospectively by reviewing an electronic register containing the results of bacterial culture and antibiotic susceptibility testing of biological specimens received from healthcare facilities during 2018–2019. Results: Of the 37,798 biological specimens with bacterial culture growth, 22% (8244) were Gram-positive. Among the Gram-positive bacteria, 42% (2801) were SA, of which 48% (1331) were judged as MRSA by phenotypic methods. The prevalence of MRSA was higher in the older age groups, in female patients, in urine specimens and specimens received from the intensive care unit and dermatology departments. One site (Site F) had the highest MRSA prevalence of the seven AMR sentinel sites. Most SA isolates were sensitive to vancomycin (90%) by phenotypic methods. Conclusions: The high prevalence of MRSA indicates a major public health threat. There is an urgent need to strengthen the AMR surveillance and hospital infection control program in Myanmar.

Virulence and Drug-Resistance of Staphylococcus aureus Strains Isolated from Venous Ulcers in Polish Patients

Infected chronic venous ulcers (VUs) represent a major health problem. We analysed the aerobic microbiome in the VUs, the virulence, and drug-resistance of Staphylococcus aureus (SA) strains. Swabs from 143 outpatients and inpatients Polish subjects were collected. SA strains were tested for drug sensitivity using a phenotyping method and for methicillin-resistant SA (MRSA) and macrolide-lincosamide-streptogramin B (MLSB) resistance using PCR. We analysed virulence genes, the genetic similarity of strains, and performed Staphylococcal cassette chromosome mec typing and Staphylococcal protein A typing. SA was isolated as a single one in 34.9% of cases, 31.5% paired with another pathogen, and 33.6% S. aureus combined with at least two other strains. The majority of SA isolates (68.5%) possessed the virulence lukE gene. Drug resistance was significantly common in hospitalised than in ambulatory patients (OR 3.8; 95%CI 1.8–7.91). MLSB (altogether in 19.6% isolates) were observed mostly in non-hospitalised patients (OR 9.1; 95%CI 1.17–71.02), while MRSA was detected in 11.9% of strains equally. Hospitalisation and patient’s age group (aged > 78.0 or < 54.5 years) were significant predictors of the multi-drug resistant SA (MDR-SA). Over 30% of the infected VUs were associated with multi-species biofilms and presence of potentially highly pathogenic microorganisms. Elderly hospitalised patients with chronic venous ulcers are prone to be infected with a MDR-SA.

Evaluation of the role of staphylococci in the pathomechanism of conjunctivitis

PurposeDetermination of the association between ica genes and phenotypic biofilm formation in staphylococcal isolates involved in conjunctivitis, their antibiotic resistance as well as detection of selected virulence characteristics: adhesion to epithelial cells and in vitro cytotoxicity.MethodsThe study included 26 Staphylococcus aureus (SA) and 26 Staphylococcus epidermidis (SE) isolates. The presence of icaAD genes and ica operon was determined by the PCR assay. Phenotypic biofilm formation was verified using the microtitre plate assay. Antibiotic resistance was performed using the disc diffusion method. Staphylococcal ability to attach to host cells was assessed by flow cytometry. Cytotoxicity on epithelial cells was evaluated by LDH assay.ResultsThe ica genes were detected in 26.9% of SE and in 42.3% of SA isolates. Only 15.3% of isolates (SE) were positive for both the icaAD and the ica operon. Phenotypically, 19.2% of SE isolates were strong biofilm producers, among which three were both icaAD- and ica operon-positive. About 26.9% of SA isolates were strong biofilm producers. Methicillin resistance (MR) was detected in 34.6% of SE and 26.9% of SA isolates. About 75% of MR isolates were multidrug resistant. SA isolates adhered to host cells more extensively than SE. SA isolates released higher level of LDH than SE.ConclusionsAdherence abilities were commonly observed in staphylococci associated with conjunctivitis. However, low prevalence of isolates positive for a complete and functional ica locus and low prevalence of strong biofilm producers was detected. SA adhered to a greater extent to eukaryotic cells than SE and were more cytotoxic.

Prevalence and Genetic Characteristics of Staphylococcus aureus CC398 Isolates From Invasive Infections in Spanish Hospitals, Focusing on the Livestock-Independent CC398-MSSA Clade.

BackgroundLivestock-associated (LA)-CC398-MRSA is closely related to pigs, being unfrequently detected in human invasive infections. CC398-MSSA is emerging in human invasive infections in some countries, but genetic and epidemiological characteristics are still scarcely reported.ObjectivesTo determine the prevalence of Staphylococcus aureus (SA) CC398, both MRSA and MSSA, among blood cultures SA isolates recovered in Spanish hospitals located in regions with different pig-farming densities (PD) and characterize the recovered isolates.MethodsOne thousand twenty-two SA isolates (761 MSSA, 261 MRSA) recovered from blood cultures during 6–12 months in 17 Spanish hospitals (2018–2019) were studied. CC398 lineage identification, detection of spa-types, and antibiotic resistance, virulence and human immune evasion cluster (IEC) genes were analyzed by PCR/sequencing.ResultsForty-four CC398-MSSA isolates (4.3% of SA; 5.8% of MSSA) and 10 CC398-MRSA isolates (1% of SA; 3.8% of MRSA) were detected. Eleven spa-types were found among the CC398-MSSA isolates with t571 and t1451 the most frequent spa-types detected (75%). Most of CC398-MSSA isolates were Immune-Evasion-Cluster (IEC)-positive (88.6%), tetracycline-susceptible (95.5%) and erythromycin/clindamycin–inducible-resistant/erm(T)-positive (75%). No statistical significance was detected when the CC398-MSSA/MSSA rate was correlated to PD (pigs/km2) (p = 0.108). On the contrary, CC398-MRSA isolates were all IEC-negative, predominately spa-t011 (70%), and the CC398-MRSA/MRSA rate was significantly associated to PD (p < 0.005).ConclusionCC398-MSSA is an emerging clade in invasive infections in Spanish hospitals. CC398-MRSA (mostly t011) and CC398-MSSA (mostly t571 and t1451) show important differences, possibly suggesting divergent steps in host-adaptation evolutionary processes. While CC398-MRSA is livestock-associated (lacking IEC-system), CC398-MSSA seems to be mostly livestock-independent, carrying human-adaptation markers.

S. pseudintermedius and S. aureus lineages with transmission ability circulate as causative agents of infections in pets for years

BackgroundStaphylococcus pseudintermedius (SP) and Staphylococcus aureus (SA) are common colonizers of companion animals, but they are also considered opportunistic pathogens, causing diseases of diverse severity. This study focused on the identification and characterization of 33 coagulase-positive staphylococci isolated from diseased pets (28 dogs and five cats) during 2009–2011 in a veterinary hospital in Spain in order to stablish the circulating lineages and their antimicrobial resistance profile.ResultsTwenty-eight isolates were identified as SP and five as SA. Nine methicillin-resistant (MR) isolates (27%) carrying the mecA gene were detected (eight MRSP and one MRSA). The 55% of SP and SA isolates were multidrug-resistant (MDR). MRSP strains were typed as ST71-agrIII-SCCmecII/III-(PFGE) A (n=5), ST68-agrIV-SCCmecV-B1/B2 (n=2), and ST258-agrII-SCCmecIV-C (n=1). SP isolates showed resistance to the following antimicrobials [percentage of resistant isolates/resistance genes]: penicillin [82/blaZ], oxacillin [29/mecA] erythromycin/clindamycin [43/erm(B)], aminoglycosides [18–46/aacA-aphD, aphA3, aadE], tetracycline [71/tet(M), tet(K)], ciprofloxacin [29], chloramphenicol [29/catpC221], and trimethoprim-sulfamethoxazole [50/dfrG, dfrK]. The dfrK gene was revealed as part of the radC-integrated Tn559 in two SP isolates. Virulence genes detected among SP isolates were as follow [percentage of isolates]: siet [100], se-int [100], lukS/F-I [100], seccanine [7], and expB [7]. The single MRSA-mecA detected was typed as t011-ST398/CC398-agrI-SCCmecV and was MDR. The methicillin-susceptible SA isolates were typed as t045-ST5/CC5 (n=2), t10576-ST1660 (n=1), and t005-ST22/CC22 (n=1); the t005-ST22 feline isolate was PVL-positive and the two t045-ST45 isolates were ascribed to Immune Evasion Cluster (IEC) type F. Moreover, the t10576-ST1660 isolate, of potential equine origin, harbored the lukPQ and scneq genes. According to animal clinical history and data records, several strains seem to have been acquired from different sources of the hospital environment, while some SA strains appeared to have a human origin.ConclusionsThe frequent detection of MR and MDR isolates among clinical SP and SA strains with noticeable virulence traits is of veterinary concern, implying limited treatment options available. This is the first description of MRSA-ST398 and MRSP-ST68 in pets in Spain, as well the first report of the dfrK-carrying Tn559 in SP. This evidences that current transmissible lineages with mobilizable resistomes have been circulating as causative agents of infections among pets for years.

327. Oritavancin Activity against Staphylococcus aureus Isolates Causing Bone and Joint Infections in European Hospitals (2010–2019)

BackgroundBone and joint infections (BJI) frequently are caused by Staphylococcus aureus (SA), and since prolonged therapy courses typically are required, agents with convenient administration are preferred. Oritavancin (ORI) is a long-acting lipoglycopeptide approved as a single dose regimen for treating skin and skin structure infections. This study evaluates the activity of ORI and comparators against SA causing BJI in European (EU) hospitals.MethodsA total of 575 SA isolates from the SENTRY Antimicrobial Surveillance Program causing BJI in 15 EU countries from 2010 to 2019 were included. Bacterial identification was confirmed by MALDI-TOF MS. Broth microdilution susceptibility (S) testing and interpretation was performed following current CLSI guidelines. The activities of ORI and comparators were evaluated across the years and by EU region: western Europe (W-EU; 491 isolates) and eastern EU/Mediterranean region (E-EU; 84 isolates).ResultsMethicillin resistance (MRSA) was observed in 20.5% of SA (18.5% in W-EU and 32.1% in E-EU), ranging from 31.1% in 2011 to 14.6% in 2016. MRSA rates were slightly lower in 2016–2019 (14.6%-19.2%) than previous years (2011–2013; 24.4%-31.1%). ORI exhibited 100.0% susceptibility across the entire SA collection with yearly MIC50 and MIC90 variations within 1 doubling dilutions (MIC50 and MIC90, 0.015–0.03 and 0.03–0.06 mg/L, respectively), regardless the MRSA phenotype or EU region. Daptomycin, vancomycin, teicoplanin, and linezolid also showed complete coverage against SA. Clindamycin (CLI; >99.0%S) and levofloxacin (> 95.0%S) were active against methicillin-susceptible SA, but less active against MRSA (67.8%S and 16.1%S, respectively). E-EU MRSA isolates displayed lower S rates than W-EU MRSA isolates to ceftaroline (83.3% vs. 90.6%), CLI (44.4% vs. 74.7%) and tetracycline (66.7% vs. 89.0%), respectively.ConclusionMRSA rates among isolates causing BJI varied within regions. Although several drugs were in vitro active against MSSA, options remained limited against MRSA. ORI showed in vitro activity against the entire collection of European SA isolates and may be a consideration for treating BJI with the convenience of drug administration.Table 1 DisclosuresCecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

333. Tedizolid Activity against Gram-Positive Bacterial Isolates Causing Bone and Joint Infections in the United States (2015–2019)

BackgroundProlonged systemic antibiotic courses are frequently used to manage difficult-to-treat bone and joint infections (BJI). Tedizolid has been considered as a therapy candidate for BJI in adults and children. This study assessed the in vitro activity of tedizolid and comparator agents against a contemporary collection of Gram-positive (GP) isolates causing BJI in the US.MethodsA total of 310 Staphylococcus aureus (SA), 79 β-hemolytic streptococci (BHS), 52 coagulase-negative staphylococci (CoNS), and 37 Enterococcus faecalis isolates were included in this study. These isolates were collected from patients with BJI from 30 medical centers in the US between 2015 and 2019 as a part of the Surveillance of Tedizolid Activity and Resistance (STAR) Program. Bacterial identification was confirmed by MALDI-TOF MS. MIC results were obtained by reference CLSI broth microdilution methods and interpretations used CLSI guidelines.ResultsTedizolid (MIC50/90, 0.12/0.25 mg/L) inhibited all SA at the CLSI breakpoint (≤0.5 mg/L) including methicillin-resistant SA (MRSA; 35.8% of SA; MIC50/90, 0.12/0.25 mg/L). Linezolid, vancomycin, and daptomycin had 100% susceptibility rates against SA isolates (Table). All CoNS isolates were inhibited by tedizolid at ≤0.5 mg/L. Tedizolid was active against all BHS (100% susceptible) as follows: S. pyogenes (n=24; MIC50/90, 0.12/0.25 mg/L), S. agalactiae (n=44; MIC50/90, 0.12/0.25 mg/L), and S. dysgalactiae (n= 11; MIC50/90, 0.25/0.25 mg/L). Penicillin, linezolid, vancomycin, and daptomycin also were active against BHS (100% susceptible). Tedizolid (MIC50/90, 0.25/0.25 mg/L; 100% susceptible) was 4- to 8-fold more potent than linezolid (MIC50/90, 1/1 mg/L) and vancomycin (MIC50/90, 1/2 mg/L) against E. faecalis. GP isolates resistant to oxazolidinone were not observed.ConclusionTedizolid demonstrated potent in vitro activity against this collection of contemporary GP isolates causing BJI in US hospitals. Tedizolid and comparator agents showed high susceptibility rates against the most frequent organisms and organism groups, including MRSA. These findings support the clinical development of tedizolid as an additional option for treating BJI caused by GP pathogens.Table 1 DisclosuresCecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Loranthus acaciae: Alternative medicine for β-lactamase producer and methicillin-resistant Staphylococcus aureus.

Recently, we reported high antibacterial efficiency of Loranthus acaciae (LA) against different standard strains of bacteria including Methicillin-Resistant Staphylococcus aureus (MRSA). Therefore, this study aimed to confirm the effectiveness of LA against clinically isolated Staphylococcus aureus (SA) including β-lactamase producer (Blac) and MRSA. Forty-eight SA isolates collected from various clinical samples were used in this study. Antibiotics susceptibility profile was determined for twenty different antibiotics using automated Microscan Walkaway 96 Plus system as recommended by Clinical and Laboratory Standards Institute (CLSI) guidelines. This system also identified β-lactamase producers and MRSA. In the meantime, LA ethanolic extract was fractionated using liquid–liquid fraction method to hexane, dichloromethane DCM and methanol 80% fractions. Antimicrobial activities of LA extract and fraction were performed with agar well diffusion method for all SA isolates, MIC and MBC were also recorded. Phytochemical screening for various phyto-constituent classes of LA ethanolic extract was determined. Out of 48 SA isolates, Cefoxitin-positive MRSA represent 31 (64.6%), Blac 17 (35.4%), and 41 (85.4%) were multidrug-resistant SA, which was resistant at least to one antibiotic from three different categories. All isolates were resistant to ampicillin and penicillin. Antimicrobial activities of LA extract and fractions revealed that ethanol extract was active against all isolated SA with inhibition zone ranged from 33 ± 2.00 to 25 ± 3.05 mm. While DCM exhibited the largest inhibition zone range from 37 ± 3.00 to 33 ± 2.00 mm. This study is first of its kind conforming the high antibacterial activity of LA against SA isolated from a different source of infection. The study concluded that LA extract and fractions are active and give positive result for all isolated SA. Therefore, suitable pharmacological formulation of LA extract as a promising antibacterial agent for the treatment of SA infection should be given extreme priority.

Occurrence and characterisation of methicillin-resistant Staphylococcus aureus isolated from bovine milk in Hungary.

The last surveys on methicillin-resistant Staphylococcus aureus (MRSA) isolated from bovine milk in Hungary took place in the 2000s. To elucidate the genetic variability and to estimate the burden of the pathogen, MRSA from our strain collection and prospectively collected Staphylococcus aureus (SA) isolates originating from two milk hygiene laboratories were investigated. Between 2003 and 2018, 27 MRSA strains originating from 10 dairy farms were deposited and characterised. Most strains (n = 20) belonged to ST1-t127-SCCmecIV and were recovered from three unrelated farms. From other farms, variable genotypes were identified sporadically: ST22-t032-SCCmecIV from three farms; a newly described double locus variant of ST97, ST5982-t458-SCCmecIV from two farms; and ST398-t011-SCCmecIV and ST398-t011-SCCmecV from two respective farms. The prospective screening of 626 individual SA isolates originating from 42 dairy farms resulted in four (0.48 %) MRSA strains from three (7.14 %) farms. All MRSA isolates belonged to the clonal complex 398 and a novel spa-type t19251 was also identified. Most isolates were resistant to three or more antimicrobial classes. The occurrence and significance of MRSA of dairy origin seems to be unchanged in the past decade in Hungary. However, the low host specificity and multiresistance of the identified genotypes calls for periodic revision on the role and distribution of the pathogen in the Hungarian dairy sector.

Impact of Coexistence Phenotype Between Staphylococcus aureus and Pseudomonas aeruginosa Isolates on Clinical Outcomes Among Cystic Fibrosis Patients.

Staphylococcus aureus (SA) is the major colonizer of the lungs of cystic fibrosis (CF) patients during childhood and adolescence. As patients age, the prevalence of SA decreases and Pseudomonas aeruginosa (PA) becomes the major pathogen infecting adult lungs. Nonetheless, SA remains significant and patients harboring both SA and PA are frequently found in the worldwide cohort. The overall impact of co-infection remains controversial. Furthermore, co-infecting isolates may compete or coexist. The aim of this study was to analyse if co-infection and the coexistence of SA and PA could lead to worse clinical outcomes. The clinical and bacteriological data of 212 Lyon CF patients were collected retrospectively, and patients were ranked into three groups, SA only (n = 112), PA only (n = 48) or SA plus PA (n = 52). In addition, SA and PA isolates from co-infected patients were tested in vitro to define their interaction profile. Sixty five percent (n = 34) of SA/PA pairs coexist. Using univariate and multivariate analysis, we confirm that SA patients have a less severe clinical condition than others, and PA induces a poor outcome independently of the presence of SA. Regarding co-infection, no significant difference in clinical outcomes was observed between patients with coexisting pairs and patients with competitive pairs. However, when compared to SA mono-infected patients, patients with coexisting pair presented higher frequency and length of hospitalizations and more exacerbations. We suggest that coexistence between SA and PA may be an important step in the natural history of lung bacterial colonization within CF patients.

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.

1563. Population Pharmacokinetics and Pharmacodynamics of Daily and Extended Interval Dalbavancin Dosing Regimens for Salvage Therapy of Staphylococcus aureus Endocarditis: Mechanistic Modeling of Rabbit Infection Data to Support Human Dosing Regimens

BackgroundDalbavancins’ (DAL) long half-life and favorable susceptibility profile makes it an attractive option for salvage therapy for endocarditis caused by Staphylococcus aureus (SA), including those with elevated vancomycin (VAN) MIC. The aim of our study was to establish the PKPD of DAL based on a rabbit model of infection and extrapolate those results to the design of human treatment regimens.MethodsData from a rabbit endocarditis model of SA with VAN MICs of 2 and 8 mg/L were fitted using an inoculum-size dependent model and the Pmetrics software. Then, the results were linked to a human PK model to simulate regimens with or without a loading dose. Probability of target attainment (PTAs) for achieving bacterial density of <2 log CFU per gram of vegetation was compared with outcomes based on standard antibiotic therapy (SAT) at 3, 10, 21, 31, and 42 days.ResultsMean (SD) PTAs of 34.3% (10.5%), 61.3% (7.0%), 73.5% (5.4%), 79.5% (4.3%), and 83.1% (3.4%) were estimated for all regimens combined with maximum PTAs of 41.8%, 63.6%, 77.8%, 86.6%, and 88.9% for the highest weekly dose at 3, 10, 21, 31 and 42 days of therapy, respectively. While all approaches should achieve an adequate probability of clearing of the colonies by day 21, only doses near 2,000 mg/week are likely to approximate sterilization rates similar to that expected by the SAT at day 42. We observed no meaningful differences in PTAs for weekly vs. daily dosing given with a load. Also, increasing the total weekly dose over 2,000 mg seems to offer minimal additional benefit (Figure 1A–D). Trough-level accumulation is expected as total weekly doses increase, showing a median (IQR) of 62.6 (73.1,85.2) [101.8 (89.9,117.4)] mg/L and 106.5 (91.63,123.6) [135.3 (118.3,156.0)] mg/L at 42 days for the 1,000 mg and 1,500 mg weekly [in equal daily fractions] doses, respectively.ConclusionOur design suggests that these DAL dosing regimens in humans are likely to provide reasonable rates of sterilization when treating endocarditis caused by SA isolates, and administration of near 2,000 mg weekly doses may be considered to improve upon sterilizing effect, but at the cost of accumulating DAL levels. Efficacy and safety of new regimens should be confirmed in well-controlled clinical trials. Disclosures All authors: No reported disclosures.

1583. Eight Years of Sustained Potency and Activity of Oritavancin against Gram-Positive Isolates Causing Bacteremia and Endocarditis in the USA, Including Enterococcal Infections Requiring an Optimized Dosing Strategy for Daptomycin

BackgroundOritavancin (ORI) is a potent lipoglycopeptide with desirable PK/PD parameters for treating serious gram-positive infections. This study assessed the activity of ORI against Staphylococcus aureus (SA), Enterococcus faecalis (EF), and E. faecium (EFM) causing bloodstream infection (BSI), including infective endocarditis (IE) and daptomycin (DAP)- susceptible dose-dependent (SDD) vancomycin-resistant (VRE) subsets. We also evaluated the longitudinal activity of ORI.MethodsA total of 5,469 SA, 1,157 EF, and 721 EFM were recovered from BSI in 35 US sites (2011–2018). Subsets of SA isolates causing IE (84) and EFM displaying DAP-SDD-VRE phenotypes (230) were included. Identification was confirmed by MALDI-TOF MS and isolates were tested for susceptibility (S) according to CLSI.ResultsOverall, ORI showed similar MIC50 (0.03 mg/L) and MIC90 results (0.06 mg/L) against MRSA and MSSA (figure) and the SA EC subset (41.7% MRSA; data not shown). Similar findings were noted for ORI tested against EF DAP-S (MIC50/90, 0.015/0.06 mg/L) and DAP-SDD (MIC50/90, 0.015/0.06 mg/L). ORI MIC values against DAP- and VAN-S EFM (MIC50/90, ≤0.008/0.015 mg/L) were at least 8-fold lower than those from DAP-SDD-VRE isolates (MIC50/90, 0.06/0.12 mg/L; 31.9% of all EFM), and all EFM were inhibited by ORI at ≤0.25 mg/L. The longitudinal analysis showed MRSA rates varying from 39.7% (2017) to 46.8% (2011), while the annual ORI MIC50 and MIC90 results were 0.015–0.06 mg/L and 0.03–0.12 mg/L, respectively, against MRSA during the 8-year period. ORI yearly MIC50 and MIC90 results were 0.015–0.03 mg/L and 0.03–0.12 mg/L against EF, respectively. MIC50 and MIC90 results of 0.008–0.03 mg/L and 0.03–0.12 mg/L, respectively, were obtained for ORI against the DAP-SDD EF subset each year. ORI MIC50 and MIC90 results of 0.03–0.06 and 0.06–0.12 mg/L were obtained annually against DAP-SDD-VRE (EFM), respectively.ConclusionORI showed a potent activity against this collection of isolates causing BSI and IE in the USA, including resistant subsets requiring higher dosage regimens when treating serious infections. In addition, ORI maintained a stable potency throughout the 8-year study period with no apparent temporal trends. Disclosures All authors: No reported disclosures.

Changing antibiotic resistance patterns for Staphylococcus aureus surgical site infections.

Beta-lactam antibiotics such as cefazolin are first-line agents for preoperative prophylaxis, whereas clindamycin is often administered to patients with a reported penicillin allergy. 1 Recent studies have reported increased resistance to clindamycin in Staphylococcus aureus (SA) isolates from both pediatric and adult populations, and these changes may have implications for surgical site infection (SSI) prophylaxis and empirical management. 2 , 3 Antibiotic resistance trends of SA isolates recovered from SSIs in adults in the United States have not been recently described.

Associations of pathogen-specific and host-specific characteristics with disease outcome in patients with Staphylococcus aureus bacteremic pneumonia.

ObjectiveTo understand the relationships of Staphylococcus aureus (SA) bacteremic pneumonia (SABP) outcome with patient‐specific and SA‐specific variables.MethodsWe analysed SA bloodstream isolates and matching sera in SABP patients by sequencing SA isolates (n = 50) and measuring in vitro AT production, haemolytic activity and expression of ClfA and ClfB. Controls were sera from gram‐negative bacteremia patients with or without pneumonia and uninfected subjects. Levels of IgGs, IgMs and neutralizing antibodies (NAbs) against SA antigens were quantified and analysed by one‐way ANOVA. Associations of patient outcomes with patient variables, antibody levels and isolate characteristics were evaluated by univariate and multivariate logistic regression analyses.ResultsSABP patients had higher levels of IgGs against eight virulence factors and anti‐alpha toxin (AT) NAbs than uninfected controls. Levels of IgG against AT and IgMs against ClfA, FnbpA and SdrC were higher in clinically cured SABP patients than in clinical failures. Anti‐LukAB NAb levels were elevated in all cohorts. Increased odds of cure correlated with higher haemolytic activity of SA strains, longer time between surgery and bacteremia (> 30 days), longer duration of antibiotic therapy, lower acute physiology and total APACHE II scores, lack of persistent fever for > 72 h and higher levels of antibodies against AT (IgG), ClfA (IgM), FnbpA (IgM) and SdrC (IgM).DiscussionLimitations included the cross‐sectional observational nature of the study, small sample size and inability to measure antibody levels against all SA virulence factors.ConclusionOur results suggest that SABP patients may benefit from immunotherapy targeting multiple SA antigens.