Pivotal Role of Translation in Anti-Infective Development.

The value of model-based translation in drug discovery and development is now effectively being recognized in many disease areas and among various stakeholders. Such quantitative approaches are expected to facilitate the selection on which compound to prioritize for successful development, predict the human efficacious dose based on preclinical data with adequate precision, guide design, and de-risk later development stages. The importance of time-dependencies, which are typically species-dependent due to different turnover rates of biological processes, is, however, often neglected. For bacterial infections, the choice of dosing regimen is typically relying on preclinical pharmacokinetic (PK) and pharmacodynamic (PD) data, because the bacterial load and disease severity, and consequently the PK/PD relationship, cannot be quantified well on clinical data, given the low-information end points used. It is time to recognize the limitations of using time-collapsed approaches for translation (i.e., methods where targets are based on summary measures of exposure and response). Models describing the full time-course captures important quantitative information of drug distribution, bacterial growth, antibiotic killing, and resistance development, and can account for species-differences in the PK profiles driving the killing. Furthermore, with a model-based approach for translation, we can take a holistic approach in development of a joint model for in vitro, in vivo, and clinical data, as well as incorporating information on the contribution of the immune system. Such advancements are anticipated to facilitate rational decision making during various stages of drug development and in the optimization of treatment regimens for different groups of patients.

Vaginitis: Review on Drug Resistance.

Female genital tract infections have a high incidence among different age groups and represent an important impact on public health. Among them, vaginitis refers to inflammation of the vulva and/or vagina due to the presence of pathogens that cause trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis. Several discomforts are associated with these infections, as well as pregnancy complications and the facilitation of HIV transmission and acquisition. The increasing resistance of microorganisms to drugs used in therapy is remarkable, since women report the recurrence of these infections and associated comorbidities. Different resistant mechanisms already described for the drugs used in the therapy against Trichomonas vaginalis, Candida spp., and Gardnerella vaginalis, as well as aspects related to pathogenesis and treatment, are discussed in this review. This study aims to contribute to drug design, avoiding therapy ineffectiveness due to drug resistance. Effective alternative therapies to treat vaginitis will reduce the recurrence of infections and, consequently, the high costs generated in the health system, improving women's well-being.

Association between antimicrobial drug class for treatment and retreatment of bovine respiratory disease (BRD) and frequency of resistant BRD pathogen isolation from veterinary diagnostic laboratory samples.

Although 90% of BRD relapses are reported to receive retreatment with a different class of antimicrobial, studies examining the impact of antimicrobial selection (i.e. bactericidal or bacteriostatic) on retreatment outcomes and the emergence of antimicrobial resistance (AMR) are deficient in the published literature. This survey was conducted to determine the association between antimicrobial class selection for treatment and retreatment of BRD relapses on antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Pathogens were isolated from samples submitted to the Iowa State University Veterinary Diagnostic Laboratory from January 2013 to December 2015. A total of 781 isolates with corresponding animal case histories, including treatment protocols, were included in the analysis. Original susceptibility testing of these isolates for ceftiofur, danofloxacin, enrofloxacin, florfenicol, oxytetracycline, spectinomycin, tilmicosin, and tulathromycin was performed using Clinical and Laboratory Standards Institute guidelines. Data were analyzed using a Bayesian approach to evaluate whether retreatment with antimicrobials of different mechanistic classes (bactericidal or bacteriostatic) increased the probability of resistant BRD pathogen isolation in calves. The posterior distribution we calculated suggests that an increased number of treatments is associated with a greater probability of isolates resistant to at least one antimicrobial. Furthermore, the frequency of resistant BRD bacterial isolates was greater with retreatment using antimicrobials of different mechanistic classes than retreatment with the same class. Specifically, treatment protocols using a bacteriostatic drug first followed by retreatment with a bactericidal drug were associated with a higher frequency of resistant BRD pathogen isolation. In particular, first treatment with tulathromycin (bacteriostatic) followed by ceftiofur (bactericidal) was associated with the highest probability of resistant M. haemolytica among all antimicrobial combinations. These observations suggest that consideration should be given to antimicrobial pharmacodynamics when selecting drugs for retreatment of BRD. However, prospective studies are needed to determine the clinical relevance to antimicrobial stewardship programs in livestock production systems.

'Agricultural Waste to Treasure' - Biochar and eggshell to impede soil antibiotics/antibiotic resistant bacteria (genes) from accumulating in Solanum tuberosum L.

Soil contamination with antibiotics and antibiotic resistant bacteria/genes (ARB/ARGs) has becoming an emerging environmental problem. Moreover, the mixed pollutants' transfer and accumulation from soil to tuberous vegetables has posed a great threat against food security and human health. In this work, the application of two absorbing materials (maize biochar and sulfate modified eggshell) was able to reduce the poisonous effect of soil antibiotics on potato root system by stimulate the dissipation of water-soluble antibiotics in soil; and also improve food quality by increasing potato starch, protein, fat, and vitamins. Meanwhile, both amendments could effectively decrease the classes and the accumulative abundance of ARB and ARGs (sulI, sulII, catI, catII, ermA, ermB) in the edible parts of potato. The lowest abundance of ARGs was detected in the biochar application treatment, with the accumulative ARG level of 8.9 × 102 and 7.2 × 102 copies mL-1 in potato peel (sull + catI + ermA) and tuberous root (sulI), respectively. It is the first study to demonstrate the feasibility of biochar and eggshell derived from agricultural wastes as green absorbing materials to reduce soil antibiotic, ARB, and ARGs accumulation risk in tuberous vegetable.

Biophysical and biochemical characterization of Rv3405c, a tetracycline repressor protein from Mycobacterium tuberculosis.

Mycobacterium tuberculosis, the causative agent of tuberculosis disease, is one among the deadliest pathogens in the world. Due to long treatment regimen, HIV co-infection, persistence of bacilli in latent form and development of XDR and TDR strains of Mtb, tuberculosis has posed serious concerns for managing the disease, and calls for discovery of new drugs and drug targets. Using a computational pipeline involving analysis of the structural models of the Mtb proteome and an analysis of the ATPome, followed by a series of filters to identify druggable proteins, solubility and length of the protein, several candidate proteins were shortlisted. From this, Rv3405c, a tetR family of DNA binding protein involved in antibiotic resistance, was identified as one of the good drug targets. Rv3405c binds to the upstream non-coding region of Rv3406 and causes repression of Rv3406 activity there by affecting the downstream processes involved in antibiotic resistance was further characterized. The Rv3405c gene was cloned; the gene product was over-expressed in E. coli and purified by Ni NTA chromatography. DNA binding studies by EMSA showed that the recombinant Rv3405c protein binds to the DNA sequence corresponding to the promoter region of Rv3406 and upon addition of tetracycline, the DNA binding activity was lost. ß-galactosidase reporter assay in E. coli using both wild type and a DNA binding defective mutant protein indeed proved that Rv3405c acts as a repressor.

Common microbial causes of significant bacteriuria and their antibiotic resistance pattern in the Isfahan Province of Iran.

Urinary tract infections (UTIs) are considered the most common community-acquired infections worldwide, which have possible complications along with significant economic impact on national healthcare systems. The aim of this study was to identify the most common causes of significant bacteriuria and to assess their antimicrobial resistance pattern in the Isfahan province of Iran. In this cross-sectional study, 11,678 urine samples of the patients referred to Mahdieh Medical Diagnostic Centre Charity were examined over a period of 10 months (from September 2015 to June 2016). Among the cases, 6.85% were positive for bacteriuria (F/M = 11.3). Escherichia coli (62%) was the most frequently isolated bacteria, followed by Staphylococcus epidermidis (13.9%) and Staphylococcus aureus (6.8%). E. coli was more prevalent among patients with diabetes mellitus. E. coli isolates showed the highest resistance to nalidixic acid, Trimethoprim/Sulfamethoxazole and Cefixime. Our results revealed that broad-spectrum antibiotic resistance is frequent among isolated uropathogens in Isfahan, Iran.

Ciprofloxacin resistance and gonorrhea incidence rates in 17 cities, United States, 1991-2006.

Antimicrobial drug resistance can hinder gonorrhea prevention and control efforts. In this study, we analyzed historical ciprofloxacin resistance data and gonorrhea incidence data to examine the possible effect of antimicrobial drug resistance on gonorrhea incidence at the population level. We analyzed data from the Gonococcal Isolate Surveillance Project and city-level gonorrhea incidence rates from surveillance data for 17 cities during 1991-2006. We found a strong positive association between ciprofloxacin resistance and gonorrhea incidence rates at the city level during this period. Their association was consistent with predictions of mathematical models in which resistance to treatment can increase gonorrhea incidence rates through factors such as increased duration of infection. These findings highlight the possibility of future increases in gonorrhea incidence caused by emerging cephalosporin resistance.

[Serotype diversity and antimicrobial resistance of Streptococcus pneumoniae].

The pneumococcus (Streptococcus pneumoniae) is a common bacterial pathogen responsible for various infections, especially in children below 5 years of age. The severity of pneumococcal infections varies from self-limiting mucosal infections, including acute otitis media, sinusitis, and noninvasive pneumonia, to life-threatening invasive disease like bacteremia and meningitis. A high incidence of pneumococcal infections is combined with a constantly growing antibiotic resistance of this pathogen. The growing resistance is thought to be associated with misuse of antibiotics and emerging of resistant clones that may spread throughout the entire population. Pneumococcal polysaccharide conjugate vaccines (PCV) contain an assortment of pneumococcal capsular polysaccharides (from 7 to 13) that produce serotype-specific protective antibodies. Since early 2000's, the introduction of PCV into national immunization programs has been shown to substantially decrease the incidence of invasive pneumococcal disease and pneumococcal carriage associated with vaccine-type pneumococci in many countries. In 2014, PCV vaccination was included in the Russian national calendar of prophylactic vaccination. The present article reviews the current literature on serotype prevalence, antibiotic susceptibility, and PCV effect on the evolution of pneumococcus.

The antimicrobial susceptibility, biofilm formation and genotypic profiles of Staphylococcus haemolyticus from bloodstream infections.

We analysed the antimicrobial susceptibility, biofilm formation and genotypic profiles of 27 isolates of Staphylococcus haemolyticus obtained from the blood of 19 patients admitted to a hospital in Rio de Janeiro, Brazil. Our analysis revealed a clinical significance of 36.8% and a multi-resistance rate of 92.6% among these isolates. All but one isolate carried the mecA gene. The staphylococcal cassette chromosome mec type I was the most prevalent mec element detected (67%). Nevertheless, the isolates showed clonal diversity based on pulsed-field gel electrophoresis analysis. The ability to form biofilms was detected in 66% of the isolates studied. Surprisingly, no icaAD genes were found among the biofilm-producing isolates.

Patrones de resistencia de Neisseria gonorrhoeae aisladas en el área de Cuenca / Resistance patterns of Neisseria gonorrhoeae isolated in patients from the area of cuenca (Spain)

El artículo es un estudio retrospectivo para conocer la sensibilidad antibiótica de los aislados de Neisseria gonorhoeae de muestras genitales de pacientes durante los últimos 4 años en el área de Cuenca (España) para así establecer cuáles serían las mejores pautas de tratamiento para esta enfermedad en nuestra región. De un total de 26 cepas aisladas de Neisseria gonorrhoeae, la resistencia a fluorquinolonas fue del 61,54%. Todas las cepas fueron sensibles a cefotaxima, por lo que consideramos que el tratamiento empírico de elección de las infecciones gonocócicas no complicadas en nuestro medio debería ser las cefalosporinas de tercera generación (AU)

A retrospective study was conducted to determine the antibiotic susceptibility of Neisseria gonorrhoeae isolates from genital samples of patients over the last four years in Cuenca (Spain), in order to establish what would be the best treatment regimens for this disease in our region. Of a total of 26 isolates of Neisseria gonorrhoeae, fluoroquinolone resistance was 61.54%. All strains were susceptible to cefotaxime, so we believe that the choice of empirical treatment of uncomplicated gonococcal infections should be third generation cephalosporins in our region (AU)

Modelos matemáticos en el estudio de la resistencia a los antimicrobianos. Perspectivas a partir de un metaanálisis / Matematical modeling of antibiotic resistance. Perspectives from a meta-analysys

La resistencia a los antimicrobianos es uno de los principales problemas a los que se enfrenta la comunidad sanitaria internacional. El estudio de la resistencia se debe realizar desde un enfoque pluridisciplinar y en este sentido se analiza el papel que puede jugar la Modelización Matemática en este escenario. Así se realiza un análisis tanto cuantitativo como cualitativo de los trabajos que han aparecido en la literatura científica mediante una búsqueda en las principales bases de datos: MEDLINE, SCOPUS e ISI Web of Science. Tras el análisis realizado en este estudio se observa que son pocos los trabajos relacionados con la temática objeto de estudio pero han sido publicados en revistas de un alto impacto; asimismo podemos afirmar que el desarrollo de modelos matemáticos puede jugar un papel muy importante a la hora de analizar y estudiar tanto los tratamientos para prevenir la aparición de las resistencias como el establecimiento y evaluación de estrategias de control en ambientes hospitalarios y la predicción del comportamiento de las infecciones por cepas resistentes(AU)

The antibiotic resistance is one of the greatest challenges of the international health community. The study of antibiotic resistance must be a multidisciplinary task and, in this sense, the main goal of this work is to analyze the role that Mathematical Modeling can play in this scenario. A qualitative and cuantitative analysis of the works published in the scientific literature is done by means of a search in the most important databases: MEDLINE, SCOPUS and ISI Web of Science. Consequently, there are few papers related to our topic but the existing works have been published in high-quality and impact international journals. Moreover, we can state that mathematical models are a very important and useful tool to analyze and study both the treatments protocols for resistance prevention and the assesment of control strategies in hospital environtment, or the prediction of the evolution of diseases due to resistant strains(AU)

[Gastric MALT lymphoma: anatomo-clinical data and outcome of early stage H. pylori-associated gastric MALT-lymphoma resistant to treatment]. / Lymphome du MALT gastrique : Particularités anatomo-cliniques et évolutives des formes résistantes au traitement.

AIM: To describe the clinical, endoscopic and histological particularities of early stage HP associated gastric MALT lymphoma resistant to anti Hp treatment and identify predicting factors of resistance. METHODS: We retrospectively studied 12 patients with primary low grade gastric localized MALT lymphoma treated with anti HP treatment and diagnosed at La Rabta Hospital from 1999 to 2009. RESULTS: The ultrasonography was normal in 5 patients between the 6 responding patients. Perigastric lymph nodes were found in non responders (33.3%). Hp eradication was achieved in 66% of patients not responding while Hp was eradicated in 100% of responders. The two non-responding patients with failure of eradication of Hp had a strain resistant to Clarithromycin Hp. CONCLUSION: Predicting factors of failure of anti HP: HP resistance to antibiotics, the proximal head, and the presence of perigastric lymph nodes. Recently, chromosomal aberrations and immune-histochemical markers have been implicated as factors of non response to anti Hp.

The role of the laboratory in choosing antibiotics.

OBJECTIVE: Antimicrobial resistance is one of the biggest problem in medicine at the beginning of the third millennium. Antibiotic resistance is frequently associated with significant morbidity, longer hospitalization, excess costs and mortality. METHODS: In this work we discussed the role of clinical microbiology laboratory as an essential part for an effective infection control program, especially in management and treatment of "difficult infections". RESULTS: At present time, laboratory personnel have a broad range of new technologies that they can use to support and enhance the efforts of the infection control staff. In addition a network of established experts in the determination of antimicrobial breakpoints and in antimicrobial susceptibility testing has been constituted in Europe under the auspices of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC). CONCLUSION: Qualified personnel and new strategies to overcome drug resistance can contribute to solve the microbial infections problems.

Antibiotic resistance: an editorial review with recommendations.

Within a relatively short period of time after the first antimicrobial drugs were introduced, bacteria began exhibiting varying degrees of resistance. The excessive use (and abuse) of antibiotics in agriculture, and in both human and veterinary medicine, has played a critical causative role in the development of antibiotic resistance, which is now recognized as a global public health threat. Increasing concern over this issue should impact the practice of cutaneous medicine and surgery, as dermatologists can easily adopt new healthcare delivery patterns that might reduce the development of antibiotic resistance and still achieve acceptable treatment outcomes. Dermatologists should seriously consider any and all alternative therapies before committing to an extended course of antibiotic therapy for disease entities that are almost certainly not infectious. Conversely, dermatologists should carefully and closely adhere to dosage and duration recommendations when using antibiotics to treat a bona fide infectious disorder.

The effect of antimicrobial resistance on patient outcomes: importance of proper evaluation of appropriate therapy.

The impact of antimicrobial resistance on patient outcomes can be effectively measured only if the appropriateness of the antimicrobial therapy received is properly measured. Definition of appropriate therapy should include not only in vitro susceptibility but also the clinical adequacy of the antibiotic used, taking into account the pathogen isolated, the site of infection, known pharmacokinetic and pharmacodynamic properties of the drug, and dosing. In the absence of these data, the effect of delay or absence of appropriate therapy in patients infected with resistant bacterial pathogens is subject to confounding, and the true effect of resistance on outcomes may be obscured.

Antimicrobial therapy of salmonelloses--current state and perspectives.

Salmonellosis in humans is most often manifested as a self-limiting gastroenteritis. Antimicrobial therapy is superfluous in the milder forms of the disease and in Salmonella carriage but can be life saving for patients with septic salmonellosis and patients at risk of extraintestinal dissemination of the infection. The therapeutic approach is based on the clinical course of the disease and the patient's immune reactivity. Antimicrobial therapy is usually initiated before the in vitro susceptibility tests of the isolate become available. Currently, the drugs of choice for empiric treatment of acute infectious diarrhea, in which Salmonella spp are etiologically implicated, are fluoroquinolones in adults and third generation cephalosporins in children. Alternative treatment may use azithromycin and imipenem in life-threatening systemic Salmonella infections. Aminoglycosides are considered ineffective in gastrointestinal salmonelloses. The emerging resistance to fluoroquinolones, production of extended-spectrum beta-lactamases, and the increase of multidrug resistant Salmonella strains are major problems in the search for efficient antimicrobial therapy of Salmonella infection.

Moxifloxacin in respiratory tract infections.

Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including Gram-positive (Streptococcus pneumoniae), Gram-negative (Haemophilus influenzae, Moraxella catarrhalis), and atypical strains (Chlamydia pneumoniae, Mycoplasma pneumoniae), as well as multi-drug resistant S. pneumoniae, including strains resistant to penicillin, macrolides, tetracyclines, trimethoprim/sulfamethoxazole and some fluoroquinolones. Moxifloxacin is highly concentrated in lung tissue, and has demonstrated rapid eradication rates. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400mg/day. The ratio of the area under the concentration-time curve to MIC of moxifloxacin is the highest among the fluoroquinolones against S. pneumoniae. The clinical efficacy of moxifloxacin has been shown in controlled studies of community-acquired pneumonia (CAP), exacerbations of chronic bronchitis (CB) and acute bacterial rhinosinusitis. Moxifloxacin has demonstrated a faster resolution of symptoms in CAP and exacerbations of CB patients compared with first-line therapy. It has also demonstrated better eradication in exacerbations of CB compared with standard therapy, in particular the macrolides. Treatment guidelines should take into account the results of clinical trials with moxifloxacin in order to establish the role of this antimicrobial in the therapeutic arsenal against respiratory tract infections.

Sensibilidad microbiana de escherichia coli en bacteriurias en el área sanitaria del Bierzo en el año 2003 / Antimicrobial susceptibility of escherichia coli isolated from bacteriurias in Bierzo Health Area during 2003

OBJETIVO: Evaluar la sensibilidad a varios antibióticos en cepas de Escherichia coli aisladas en muestras de orina de pacientes hospitalarios y extrahospitalarios. MATERIAL Y MÉTODOS: Se analizaron los urocultivos positivos para Escherichia coli obtenidos de muestras de pacientes hospitalizados y atendidos en consultas externas hospitalarias y atención primaria. Se determinó la sensibilidad de este germen a diecinueve antibióticos de uso hospitalario y/o extrahospitalario. RESULTADOS: Según el origen hospitalario, consultas externas hospitalarias y atención primaria, respectivamente, la sensibilidad in vitro ha sido la siguiente: imipenem (100%, 100% y 100%; p=NS), amikacina (100%, 100% y 99,7%; p=NS), fosfomicina (98,6%, 98,4% y 99,6%; p=NS), cefepima (96%, 96,9% y 98,3%; p=NS), piperacilina-tazobactam (96%, 95,3% y 96,6%; p=NS), aztreonam (93,5%, 94,7% y 97,7%; p<0,001), ceftazidima (93,5%, 94,3% y 97,8%; p<0,001), cefotaxima (93,1%, 95% y 97,7%; p<0,001), cefixima (92,7%, 94,6% y 96,7%; p<0,05), nitrofurantoína (92%, 94,7% y 94,7%; p=NS), cefuroxima (88,4%, 93,1% y 95%; p<0,001), amoxicilina-clavulánico (87,7%, 88,7% y 93,8%; p<0,001), tobramicina (87%, 93,7% y 93,8%; p<0,001), gentamicina (85,9%, 92,8% y 93%; p<0,001), cefazolina (84,4%, 88,7% y 91,6%; p<0,01), ciprofloxacino (63,8%, 71,4%, 78,4%; p<0,001), norfloxacino (63%, 70,8 y 78,2%; p<0,001), cotrimoxazol (65,2%, 68,6% y 74,9%; p<0,01) y ampicilina (35,5%, 42,5% y 47,8%; p<0,01). (NS= No significativo). CONCLUSIONES: El tratamiento de las infecciones del tracto urinario frecuentemente se inicia de forma empírica. Por este motivo resulta esencial conocer los patrones de sensibilidad de las bacterias potencialmente causantes del cuadro

OBJECTIVE: Sensitivity to antibiotics of Escherichia coli isolated from intrahospital and extrahospital bacteriurias is analized. MATERIAL AND METHODS: Sensitivity to nineteen antibiotics used in the clinical practise was determined in strains of Escherichia coli isolated from intrahospital and extrahospital bacteriurias. RESULTS: The prevalence of in-vitro susceptibilities to antibiotics were (hospital, state health service clinic, health center-primary-care): imipenem (100%-100%-100%; p=NS), amikacin (100%-100%-99.7%; p=NS), fosfomicyn (98.6%- 98.4%-99.6%; p=NS), cefepime (96%-96.9%-98.3%; p=NS), piperacillin-tazobactam (96%-95.3%-96.6%; p=NS), aztreonam (93.5%-94.7%-97.7%; p<0.001), ceftazidime (93.5%-94.3%-97.8%; p<0.001), cefotaxime (93.1%-95%-97.7%; p<0.001), cefixime (92.7%-94.6%-96.7%; p<0.05), nitrofurantoin (92%-94.7%-94.7%; p=NS), cefuroxime (88.4%-93.1%- 95%; p<0.001), amoxicillin-clavulanic (87.7%-88.7%-93.8%; p<0.001), tobramicyn (87%-93.7%-93.8%; p<0.001), gentamcin (85.9%-92.8%-93%; p<0.001), cefazolin (84.4%-88.7%-91.6%; p<0.01), ciprofloxacin (63.8%-71.4%-78.4%; p<0.001), norfloxacin (63%-70.8%-78.2%; p<0.001), cotrimoxazole (65.2%-68.6%-74.9%; p<0.01) and ampicillin (35.5%-42.5%-47.8%; p<0.01). (*NS= No significant differences). CONCLUSIONS: The knowledge of the sensitivity of uropathogens to antimicrobians can allow us to initiate empirical therapy of urinary tract infections

Antimicrobial activity of hydrophobic xanthones from Cudrania cochinchinensis against Bacillus subtilis and methicillin-resistant Staphylococcus aureus.

Ten xanthones with one or two isoprenoid groups and a prenylated benzophenone isolated from roots of Cudrania cochinchinensis (Moraceae) were tested for their antimicrobial activities against Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds, gerontoxanthone H exhibited considerable antibacterial activity against B. subtilis (MIC = 1.56 microg/ml). Four xanthones, gerontoxanthone I, toxyloxanthone C, cudraxanthone S, and 1,3,7-trihydroxy-2-prenylxanthone, showed weak antibacterial activity against the bacterium (MICs = 3.13-6.25 microg/ml). These compounds also exhibited similar MIC values against methicillin-sensitive S. aureus, MRSAs, and Micrococcus luteus.