Replacement of nitrates and nitrites in meat-derived foods through the utilization of coagulase-negative staphylococci: A review.

Nitrates and nitrites, which are synthetic additives, are traditionally used as curing agents in meat-based products. These synthetic additives are employed in the preparation of fermented meat foods to improve quality characteristics and microbiological safety, develop distinct flavours and red-colour stability, and counteract lipid oxidation. Nitrites also display significant bacteriostatic and bactericidal action against spoilage microorganisms and foodborne pathogens (such as Clostridium botulinum and Listeria monocytogenes). However, meat curing is currently under scrutiny because of its links to cardiovascular diseases and colorectal cancer. Based on the current literature, this review provides recent scientific evidence on the potential utilisation of coagulase-negative staphylococci (CNS) as nitrate and nitrite substitutes in meat-based foods. Indeed, CNS are reported to reproduce the characteristic red pigmentation and maintain the typical high-quality traits of cured-meats, thanks to their arginine degradation pathway, thus providing the nitrite-related desirable attributes in cured meat. The alternative strategy, still based on the NOS pathway, consisting of supplementing meat with arginine to release nitric oxide (NO) and obtain a meat characterised by the desired pinkish-red colour, is also reviewed. Exploiting NOS-positive CNS strains seems particularly challenging because of CNS technological adaptation and the oxygen dependency of the NOS reaction; however, this exploitation could represent a turning point in replacing nitrates and nitrites in meat foods.

The effect of different antibiotic combinations in calcium sulfate cement on the growth of Cutibacterium acnes and Staphylococcus periprosthetic shoulder infection isolates.

BACKGROUND: Periprosthetic joint infections (PJI) of the shoulder are a devastating complication of shoulder arthroplasty and are commonly caused by Staphylococcus and Cutibacterium acnes. Absorbable calcium sulfate (CS) beads are sometimes used for delivering antibiotics in PJI. This study evaluates the in vitro effect of different combinations of gentamicin, vancomycin, and ertapenem in beads made from CS cement on the growth of C acnes and coagulase-negative Staphylococcus (CNS) strains. METHODS: Three strains of C acnes and 5 strains of CNS from clinically proven shoulder PJI were cultured and plated with CS beads containing combinations of vancomycin, gentamicin, and ertapenem. Plates with C acnes were incubated anaerobically while plates with Staphylococcus were incubated aerobically at 37 °C. Zones of inhibition were measured at intervals of 3 and 7 days using a modified Kirby Bauer technique, and beads were moved to plates containing freshly streaked bacteria every seventh day. This process was run in triplicate over the course of 56 days. Statistical analysis was conducted using SPSS v. 28 with repeated measures analysis of variance (ANOVA) and pairwise comparisons with Tukey correction. RESULTS: In experiments with C acnes, beads containing ertapenem + vancomycin and vancomycin alone formed the largest zones of inhibition over time (P < .001). In experiments with Staphylococcus, beads containing vancomycin alone formed the largest zones of inhibition over time for all 5 strains (P < .001). Zones of inhibition were 1.4x larger for C acnes than for Staphylococcus with beads containing vancomycin alone. For both C acnes and Staphylococcus, beads containing ertapenem had the strongest initial effect, preventing all bacterial growth in C acnes and almost all growth for Staphylococcus during the first week but dropping substantially by the second week. Beads containing gentamicin alone consistently created smaller zones of inhibition than beads containing vancomycin alone, with vancomycin producing zones 5.3x larger than gentamicin in C acnes and 1.3x larger in Staphylococcus (P < .001). DISCUSSION: These data suggest that for both C acnes and Staphylococcal species, CS beads impregnated with vancomycin were most effective at producing a robust antibiotic effect. Additionally, ertapenem may be a viable supplement in order to create a more potent initial antibiotic effect but is not as effective as vancomycin when used alone. Gentamicin alone was not effective in maintaining consistent and long-term antibiotic effects. These results indicate that amongst the antibiotics currently commercially available to be used with CS, vancomycin is consistently superior to gentamicin in the setting of C. acnes and CNS.

Detection of mecA positive staphylococcal species in a wastewater treatment plant in South Africa.

We investigated the prevalence of antibiotic resistant staphylococci and detection of resistant, virulence, and Spa genes in a South African wastewater treatment plant. Species identified were Staphylococcus aureus, S. lentus, S. arlettae, S. cohnii, S. haemolyticus, S. nepalensis, S. sciuri (now Mammaliicoccus sciuri), and S. xylosus. Isolates showed high resistance to methicillin (91%), ampicillin (89%), ciprofloxacin (86%), amoxycillin (80%), ceftazidime (74%), and cloxacillin (71%). Multiple antibiotic resistance (MAR) index for the isolates exceeded 0.2 (0.50-0.70). Among the isolates, 77% were mecA-positive. All S. aureus strains were positive for nuc and 7 Spa gene types. The present study highlights possibility of treated wastewaters being potential reservoir for antibiotic-resistant staphylococci. This is a cause for concern as wastewater effluents are decanted into environmental waters and these are, in many cases, used for various purposes including recreation (full contact), religious (full body submersion), and drinking water for some rural communities and water for livestock.

Prevalence of multidrug-resistant coagulase-positive staphylococci in canine and feline dermatological patients over a 10-year period: a retrospective study.

Coagulase-positive staphylococci (CPS) are common cutaneous pathogens often requiring multiple courses of antibiotics, which may facilitate selection for methicillin-resistant (MR) and/or multidrug-resistant (MDR) strains. To determine the prevalence of canine and feline MR/MDR CPS associated with skin diseases, medical records were retrospectively searched from April 2010 to April 2020. Pets with at least one positive culture for CPS were selected. Age, sex, antimicrobial sensitivity, previous history of antimicrobial/immunomodulatory medications and methicillin resistance/multidrug resistance status were recorded. Staphylococcus pseudintermedius (SP) (575/748) and Staphylococcus schleiferi (SS) (159/748) in dogs, and Staphylococcus aureus (12/22) in cats, were the most common CPS isolated. Three hundred and twenty-three out of 575 isolates were MR-SP (56.2 %), 304/575 were MDR-SP (52.8 %), 100/159 were MR-SS (62.9 %) and 71/159 were MDR-SS (44.6 %). A trend analysis showed a significant increase of resistance to oxacillin and chloramphenicol for S. pseudintermedius (r=0.86, 0.8; P=0.0007, 0.0034, respectively). Major risk factors for MDR-SP included oxacillin resistance (OR: 3; 95 % CI: 1.4-6.5; P=0.0044), positivity for PBP2a (OR: 2.3; 95 % CI: 1-5; P=0.031) and use of antibiotics in the previous year (OR: 2.8; 95 % CI: 1.3-5.8; P=0.0071). Oxacillin resistance was identified as a major risk factor for MDR-SS (OR: 8.8; 95 % CI: 3.6-21.1; P<0.0001). These results confirmed the widespread presence of MR/MDR CPS in referred dermatological patients. Judicious antibiotic use, surveillance for MR/MDR infections and consideration of alternative therapies are crucial in mitigating the development of resistant strains.

[Current practice of empiric antibiotic treatment for spondylodiscitis]. / Aktuelle Praxis der empirischen Antibiotikatherapie bei Spondylodiszitis.

BACKGROUND AND RESEARCH QUESTION: In pyogenic spondylodiscitis, infections with coagulase-negative staphylococci must be given increasing importance. Empirical antibiosis is particularly necessary in patients with severe or progressive neurological deficits or hemodynamic instability, as well as in the case of culture-negative spondylodiscitis. It is unclear whether uniform empirical antibiosis standards adapted to the resistance profiles exist in Germany. STUDY DESIGN AND METHODS: A survey on the empirical antibiotic therapy for pyogenic spondylodiscitis was conducted at German university and Berufsgenossenschaft clinics, each in the departments of orthopedics and trauma surgery. The survey results were applied to the resistance profiles of pathogens in 45 spondylodiscitis patients treated in our department between 2013 and 2020. Thus, the potential susceptibility and resistance rates were calculated for the indicated antibiotic therapies. RESULTS: Of the 71 clinics queried, a total of 44 (62.0%) responded. Sixteen different antibiotic therapies were reported as standard regimes. Among these, 14 different combination therapies were reported. The most commonly reported empirical antibiotics, namely amoxicillin/clavulanic acid or ampicillin/sulbactam (29.5%) and cephalosporins (18.2%) showed high potential resistance rates of 20.0% and 35.6%, respectively, in relation to the previously published resistance profile. The highest potential susceptibility rates were achieved with a combination of vancomycin + ampicillin/sulbactam (91.1% sensitive pathogens), vancomycin + piperacillin/tazobactam (91.1% sensitive pathogens), and ampicillin/sulbactam + teicoplanin (95.6% sensitive pathogens). One out of these combinations was reported as standard regime by three clinics (6.8%). CONCLUSION: The nationwide survey of empiric antibiotic treatment for pyogenic spondylodiscitis revealed a large heterogeneity in the standard of care. A combination of a broad-spectrum-ß-lactam antibiotic with an additional glycopeptide antibiotic may be justified.

The clinical significance of staphylococcus pettenkoferi: a retrospective review at a tertiary care medical center.

Staphylococcus pettenkoferi is a recently described coagulase-negative staphylococcal pathogen. We retrospectively reviewed 25 cases in which S. pettenkoferi was identified in routine cultures (12 blood, 13 other). Most were found with commensal flora and considered clinically insignificant, but its significance was uncertain in two cases from non-healing, deep foot wounds.

Isovitexin Is a Direct Inhibitor of Staphylococcus aureus Coagulase.

Staphylococcus aureus (S. aureus) is a major pathogen that causes human pneumonia, leading to significant morbidity and mortality. S. aureus coagulase (Coa) triggers the polymerization of fibrin by activating host prothrombin, which then converts fibrinogen to fibrin and contributes to S. aureus pathogenesis and persistent infection. In our research, we demonstrate that isovitexin, an active traditional Chinese medicine component, can inhibit the coagulase activity of Coa but does not interfere with the growth of S. aureus. Furthermore, we show through thermal shift and fluorescence quenching assays that isovitexin directly binds to Coa. Dynamic simulation and structure-activity relationship analyses suggest that V191 and P268 are key amino acid residues responsible for the binding of isovitexin to Coa. Taken together, these data indicate that isovitexin is a direct Coa inhibitor and a promising candidate for drug development against S. aureus infection.

Antibacterial and anti-biofilm activities of walnut pellicle extract (Juglans regia L.) against coagulase-negative staphylococci.

Juglans regia L. (common walnut) is a deciduous tree belonging to Juglandaceae family. Since ancient time, walnut was widely used in traditional medicine for its antioxidant, antidiabetic, antimicrobial, anti-inflammatory, anti-atherogenic and liver-protective effects. In this work, the antibacterial and anti-biofilm activities of walnuts pellicle extract against coagulase-negative staphylococci were evaluated. Qualitative chemical analysis was performed by the thin layer chromatography. UPLC-Ms/Ms was used to identify the chemical composition of J. regia extract. The total flavonoid and phenolic contents were determined by the Aluminium chloride and Folin-Ciocalteu methods, respectively. The extract showed antibacterial activity with MIC ranging from 3.60 to 461.75 µg/ml and MBC ranging from 461.75 to >461.75 µg/ml. Furthermore, it significantly reduced biofilm biomass and cell viability in a dose-dependent manner. Biological activities of J. regia extract may be due to its high flavonoid and phenolic contents. The obtained results are promising and they deserve further scientific investigations.

Baicalein mediates protection against Staphylococcus aureus-induced pneumonia by inhibiting the coagulase activity of vWbp.

The emergence and spread of multidrug-resistant Staphylococcus aureus (S. aureus) necessitate the research on therapeutic tactics which are different from classical antibiotics in overcoming resistance andtreatinginfections. In S. aureus, von Willebrand factor-binding protein (vWbp) is one of the key virulence determinants because it mediates not only the activation of thrombin to convert fibrinogen to fibrin, thereby enabling S. aureus to escape from the host immune clearance, but also the adhesion of S. aureus to host cells. Thus, vWbp is regarded as a promising druggable target to treat S. aureus-associated infections. Here we identify that baicalein, a natural compound isolated from the Chinese herb Scutellaria baicalensis, can effectively block the coagulase activity of vWbp without inhibiting the growth of the bacteria. Through thermal shift and fluorescence quenching assays, we demonstrated that baicalein directly binds to vWbp. Molecular dynamics simulations and mutagenesis assays revealed that the Asp-75 and Lys-80 residues are necessary for baicalein binding to vWbp. Importantly, we demonstrated that baicalein treatment attenuates the virulence of S. aureus and protects mice from S. aureus-induced lethal pneumonia. In addition, baicalein can improve the therapeutic effect of penicillin G by 75% in vivo. These findings indicate that baicalein might be developed as a promising therapeutic agent against drug-resistant S. aureus infections.

Clinical efficacy of teicoplanin in the treatment of bloodstream infection caused by methicillin-resistant coagulase-negative staphylococci.

Empirical combination therapy with ß-lactams and glycopeptides is recommended for patients with presumed staphylococcal bloodstream infection (BSI). While coagulase-negative staphylococci (CNS) remain susceptible to vancomycin, such isolates have become less susceptible to teicoplanin. The aim of this retrospective study was to evaluate the clinical efficacy of teicoplanin in the treatment of BSI caused by methicillin-resistant CNS according to teicoplanin susceptibility. Inclusion criteria were patients with intravascular-catheter related BSIs caused by methicillin-resistant CNS (positive for two or more specimens); teicoplanin therapy; and at least one of the signs or symptoms caused by BSI. Antimicrobial resistance was defined as minimum inhibitory concentration (MIC) ≥8 µg/mL. The primary efficacy endpoint was clinical success evaluated 2 weeks after the completion of teicoplanin therapy [test of cure (TOC)]. Resistant rate of CNS was 0% for vancomycin and 22.9% for teicoplanin, and geometric mean MICs were 1.31 µg/mL and 3.41 µg/mL, respectively (p < 0.001). The catheter was removed in all patients except one, and high early clinical response at 72 h after starting therapy was obtained irrespective of teicoplanin susceptibility. The clinical success rate at TOC was 60% in patients with BSIs caused by teicoplanin-resistant strains, while 90% in patients with BSIs caused by susceptible strains (p = 0.052). In multivariate analyses, teicoplanin resistance was significant factor for decreased clinical success at TOC (adjusted odds ratio 0.138, 95% confidence interval 0.020-0.961, p = 0.045). Because of the poor clinical efficacy of teicoplanin against teicoplanin-resistant CNS, combination therapy comprising vancomycin and ß-lactam antibiotics should be considered in presumed staphylococci BSI.

Collaboration between an antimicrobial stewardship team and the microbiology laboratory can shorten time to directed antibiotic therapy for methicillin-susceptible staphylococcal bacteremia and to discontinuation of antibiotics for coagulase-negative staphylococcal contaminants.

BACKGROUND: Rapid identification of Gram-positive cocci in clusters (GPCC) in positive blood cultures (pBC) may limit exposure to unnecessary or inappropriate antibiotics. METHODS: Inpatients with pBC showing GPCC between October 2013 and December 2017 were included. In the baseline period (BL), final ID and susceptibility results were reported in the electronic medical record (EMR) within 48 h of telephoned Gram stain report. The laboratory introduced rapid phenotypic identification and direct susceptibility testing (INT1), later replaced by PCR (INT2). In the last Intervention (INT3), Antimicrobial Stewardship Response Team (ASRT) contacted providers with PCR results and recommendations. RESULTS: Time to directed therapy (TDT) for MSSA and coagulase-negative Staphylococci (CoNS) decreased from BL to INT3 (48.5-17.9 h, 50.3-16.4 h, respectively). Time to ID from BL to INT3 for MSSA and CoNS also decreased (23.2-1.9 h, 44.7-2.8, respectively). CONCLUSIONS: TDT can be improved by modification of reporting methods with utilization of an ASRT.

Is Xpert MRSA/SA SSTI real-time PCR a reliable tool for fast detection of methicillin-resistant coagulase-negative staphylococci in periprosthetic joint infections?

Periprosthetic joint infections (PJIs) are frequently caused by methicillin-resistant coagulase-negative staphylococci (CoNS). Cultures remain the gold standard but often require a few days. Thus, a rapid test could be interesting to guide antibiotic strategy earlier. The purpose of this study was to evaluate the performances of RT-PCR Xpert® MRSA/SA technique for the detection of methicillin-resistant CoNS (MRCoNS) from deep samples in patients with PJIs. RT-PCR was tested on 72 samples. Sensitivity, specificity, positive predictive value, and negative predictive value of RT-PCR method were 0.36, 0.98, 0.90, and 0.74, respectively. Although RT-PCR may allow early microbial diagnosis of PJI due to Staphylococcus aureus (MSSA and MRSA), the low sensitivity and the high cost of this method to detect MRCoNS could limit its use in this field.

Optimizing antibiotic therapy of bacteremia and endocarditis due to staphylococci and enterococci: new insights and evidence from the literature.

Gram-positive cocci are a well-recognised major cause of nosocomial infection worldwide. Bloodstream infections due to methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative staphylococci, and multi-drug resistant enterococci are a cause of concern for physicians due to their related morbidity and mortality rates. Aim of this article is to review the current state of knowledge regarding the management of BSI caused by staphylococci and enterococci, including infective endocarditis, and to identify those factors that may help physicians to manage these infections appropriately. Moreover, we discuss the importance of an appropriate use of antimicrobial drugs, taking in consideration the in vitro activity, clinical efficacy data, pharmacokinetic/pharmacodynamic parameters, and potential side effects.

Coagulase-negative staphylococcal bloodstream infections: Does vancomycin remain appropriate empiric therapy?

OBJECTIVES: It is unknown if vancomycin minimal inhibitory concentrations (MICs) have increased in coagulase-negative staphylococci (CoNS) or whether vancomycin remains appropriate empiric therapy. METHODS: We performed a retrospective study at a single tertiary care center over 8 years. Adult inpatients with ≥2 positive blood cultures for CoNS within a 48-h period were eligible. Susceptibilities were performed by automated broth based-microdilution. Changes in antimicrobial susceptibility were analyzed using logistic regression. The clinical characteristics and outcomes of patients with bloodstream infections (BSI) were compared by MIC. RESULTS: Of 308 episodes of possible CoNS bacteremia, the vancomycin MIC was ≤1 µg/mL in 80 (26%) isolates, 2 µg/mL in 223 (72.4%) isolates and 4 µg/mL in 5 (1.6%) isolates. No isolates were resistant. We observed an 11-fold increased chance of having an isolate with a vancomycin MIC ≤1 µg/mL in 2009-2011 compared with 2004-2008 (OR 10.8, 95% CI 6.0-19.5, p < 0.05). In 152 patients with BSI, the median days of bacteremia, hospital mortality and readmissions at 30 days were similar in BSI caused by isolates with high vancomycin MICs (2-4 µg/mL) and low vancomycin MICs (≤1 µg/mL). CONCLUSIONS: We conclude vancomycin is still appropriate empiric therapy for CoNS BSIs. CoNS vancomycin MICs decreased over the study period despite widespread use of vancomycin.

Acquisition of high-level mupirocin resistance in CoNS following nasal decolonization with mupirocin.

OBJECTIVES: The association between mupirocin use and plasmid-based high-level resistance development mediated through mupA in CoNS has not been quantified. We determined acquisition of mupirocin resistance in Staphylococcus aureus and CoNS in surgery patients treated peri-operatively with mupirocin. PATIENTS AND METHODS: Patients admitted for surgery were treated with nasal mupirocin ointment and chlorhexidine soap for 5 days, irrespective of S. aureus carrier status. Nasal swabs were obtained before decolonization (T1) and 4 days after surgery (T2) and were inoculated onto agars containing 8 mg/L mupirocin. Staphylococci were identified by MALDI-TOF MS and mupirocin resistance was confirmed by Etest. RESULTS: Among 1578 surgical patients, 936 (59%) had nasal swabs obtained at T1 and T2; 192 (21%) patients carried mupirocin-resistant CoNS at T1 and 406 (43%) at T2 (P<0.001). Of 744 patients not colonized at T1, 277 acquired resistance (37%), corresponding to an acquisition rate of 7.4/100 patient days at risk. In all, 588 (97%) of 607 mupirocin-resistant CoNS had an MIC >256 mg/L (high level) and 381 of 383 (99.5%) were mupA positive. No acquisition of mupirocin resistance was observed in S. aureus. CONCLUSIONS: Acquisition of mupirocin resistance following decolonization was widespread in CoNS and absent in S. aureus. As almost all isolates harboured the mupA gene, monitoring resistance development in S. aureus when decolonization strategies containing mupirocin are used is recommended.

Effects of Yunnan Baiyao on the hemolytic phenomena and plasma clotting ability of Staphylococcus aureus / 国际检验医学杂志

Objective To Study the effect of Yunnan Baiyao on the hemolysis and plasma coagulation ability of Staphylococcus aureus.ToseeknewmechanismofYunnanBaiyao′sapplicationonthebasisofanti‐virulence.Methods 0.5MCFbacterialiquidof Staphylococcus aureus standard strains(ATCC29213) were prepared and cultured in blood agar plates which containing Yunnan Baiyao of different concentrations at 37 ℃ for 24 h .Then the diameter of hemolysis rings were measured and recorded .0 .1 MCF bacteria liquids treated with Yunan Baiyao of different concentrations were prepared ,and 20μL of the bacteria liquid were added in‐to 80 μL plasma ,then cultivated at 37 ℃ for 24 h to observe the phenomenon of solidification .Results There was significant differ‐ence among the effects of Yunan Baiyao of different concentrations on the Staphylococcus aureus hemolytic rings(P0 .05) .Conclusion Yunnan baiyao can inhibit the growth of Staphylococcus aureus and its hemolytic ability but has no significant effect on plasma clot‐ting enzyme .

Enterotoxin Production by Staphylococcus warneri CCRC 12929, a Coagulase-Negative strain.

Production of staphylococcal enterotoxin A (SEA) and enterotoxin D (SED) by Staphylococcus warneri was first examined in three different media including brain heart infusion (BHI) broth, NZ-amine (NZA) medium, and 3 + 3 medium containing 3% NZ-amine A plus 3% Hy-Case Amino. Results of these investigations revealed that S. warneri produced the highest amount of SEA in BHI broth. SED yields were higher when BHI broth or NZA medium was used as the culture medium. On the other hand, SEA and SED production was found to be lowest in 3 + 3 medium. Further study showed that the optimum pH, for both SEA production and SED production was 7.0. Addition of 10% (wt/vol) sodium chloride to BHI broth reduced enterotoxin production by S. warneri . SEA production was reduced and SED production was completely inhibited in the presence of 15% (wt/vol) NaCl. Supplementation of the media with 0.4 or 1.5 mM magnesium sulfate markedly reduced SED production by S. warneri . Reduced production of both SEA and SED was also observed when BHI broth was supplemented with 0.1 M glucose or glycerol.