Strengthening the relationship between intractable plantar keratosis and human papillomavirus.

The aim of the study was to determine the presence of human papillomavirus (HPV) in patients with intractable plantar keratosis (IPK) by comparing the histopathological findings of biopsies. A prospective, observational, and concordance study was carried out. Three different specimens were taken from each IPK. A first punch was sent for histopathological examination, and a second punch and a superficial skin scraping were both sent for HPV  polymerase chain reaction (PCR) and type determination. A total of 51 patients were included. From the histopathological examination, it was determined that 35 (68.6%) samples were diagnosed as warts and 16 (31.3%) as keratosis. However, the presence of HPV was confirmed by PCR in 49 (96.1%) and in 42 (82.4%) samples obtained by punch and superficial scraping, respectively. In the 49 PCR-positive samples, the most common HPV types were HPV1, HPV2, HPV27, HPV57, and HPV65, accounting for 81.6% of the samples. In conclusion, this study demonstrates that HPV infection and IPK lesions are very closely related. Although we cannot confirm that HPV is the cause of the development of IPK, the high prevalence of HPV observed in these lesions calls for a change to the procedures for managing IPK.

Fungal bioaerosol as an occupational hazard in the podiatrist's workplace.

Previous studies have reported the potential emission of nail dust to the indoor air of the podiatrist's workplace during nail drilling procedures. The main objective of this study was to analyse the fungal bioaerosol present in the indoor air of podiatry rooms, including during the nail drilling procedure. Seventeen private clinics were sampled in Madrid during spring and summer. The most prevalent filamentous fungi detected were Cladosporium spp. and Penicillium spp. in both seasons. The presence of Trichophyton rubrum and Trichophyton interdigitale was reported in samples during the drilling procedures, establishing a positive association with the clinical suspicion of onychomycosis (p = 0.002) and the utilization of aspiration systems (p=0.04). The present study concludes that airborne fungal concentrations in podiatrist's clinics are consistent with national and international guidance. Occupational exposure to dermatophytes may briefly occur during definite periods across the daily activity despite the use of dust aspiration systems.

Age-based inter-subject variability in platelet and white blood cell concentrations of platelet-rich plasma prepared using a new application to blood separation system.

The benefit of autologous platelet-rich plasma (PRP) treatment is still under discussion. Variations in PRP products, consequence of the lack of a standardised protocol for the multitude of commercially available blood separation systems and the lack of knowledge of the optimal composition of PRP or its suitability for the proposed indication are some of the reasons behind clinical inconsistencies. The impact of inter-subject variability in PRP has received less attention in comparison. The purpose of this study was to determine the inter-subject variability, based on age, in the concentrates prepared by a new blood concentration system. Twenty-six healthy volunteers of both genders (29-93 years) were enrolled. Whole blood (WB) was collected from each participant to prepare PRP using the Easy PRP kit. Platelets and white blood cells (WBC) from WB and PRP were analysed after split population by age; patients younger than 65 years (n = 13) and patients ≥65 years old (n = 13). Among the demographic characteristics tested, only age was significantly different between the groups. Cell capture efficiency of the system was specific for each type of blood cell and identical for both age groups. Platelets and WBC in PRP were higher than in WB (P < .001). In WB, platelets and WBC concentrations were significantly lower in older group (P ≤ .035). These differences persisted in the prepared PRP (P ≤ .004). The ageing of population has a strong influence on the haematocrit and therefore on the composition of PRP. Because the efficiency of blood separator system seems to be constant across individuals, the inter-subject haematocrit variability based on age could be used as a predictor of resulting PRP. The clinical application of PRP should be restricted to the specific cell capture capacity of the different commercial devices.

Toll-like 4 receptor inhibitor TAK-242 decreases neuroinflammation in rat brain frontal cortex after stress.

BACKGROUND: The innate immune response is the first line of defence against invading microorganisms and it is also activated in different neurologic/neurodegenerative pathological scenarios. As a result, the family of the innate immune toll-like receptors (TLRs) and, in particular, the genetic/pharmacological manipulation of the TLR-4 signalling pathway emerges as a potential therapeutic strategy. Growing evidence relates stress exposure with altered immune responses, but the precise role of TLR-4 remains partly unknown. METHODS: The present study aimed to elucidate whether the elements of the TLR-4 signalling pathway are activated after acute stress exposure in rat brain frontal cortex and its role in the regulation of the stress-induced neuroinflammatory response, by means of its pharmacological modulation with the intravenous administration of the TLR-4 specific inhibitor TAK-242. Considering that TLR-4 responds predominantly to lipopolysaccharide from gram-negative bacteria, we checked whether increased intestinal permeability and a resultant bacterial translocation is a potential regulatory mechanism of stress-induced TLR-4 activation. RESULTS: Acute restraint stress exposure upregulates TLR-4 expression both at the mRNA and protein level. Stress-induced TLR-4 upregulation is prevented by the protocol of antibiotic intestinal decontamination made to reduce indigenous gastrointestinal microflora, suggesting a role for bacterial translocation on TLR-4 signalling pathway activation. TAK-242 pre-stress administration prevents the accumulation of potentially deleterious inflammatory and oxidative/nitrosative mediators in the brain frontal cortex of rats. CONCLUSIONS: The use of TAK-242 or other TLR-4 signalling pathway inhibitory compounds could be considered as a potential therapeutic adjuvant strategy to constrain the inflammatory process taking place after stress exposure and in stress-related neuropsychiatric diseases.

Alcohol-Based Chlorhexidine and Potassium Sorbate Rub Strengthens the Effectiveness of Traditional Hand Scrubbing and Improves Long-Lasting Effectiveness-Evaluation of Hand Preparation Protocols According to EN 12791.

Despite the advantages of surgical handrub in terms of the ease of application and effectiveness, chlorhexidine (CHG)-based hand scrubbing remains the preferred method for surgical hand preparation. However, it does not systematically meet the non-inferiority requirement of the European norm (EN) 12791 with respect to n-propanol (the reference product) and does not provide the sustained efficacy expected for these long-lasting agents. Commercially available alcohol-based products have also failed to demonstrate sustained efficacy according to EN 12791. Multi-step protocols enhance the efficacy of hand scrubbing, yet their extended disinfection duration might diminish their allure for healthcare professionals. In this study, we show that hand scrubbing with CHG 4% followed by a 1 min rubbing with the novel formulation of ethanol (Et) 70%/CHG 3% plus 0.3% potassium sorbate food additive (PS) meets the non-inferiority requirement and demonstrates sustained efficacy when tested according to EN 12791. The immediate and 3 h effect of this protocol was significantly higher than that of n-propanol and the homologous disinfection protocol without PS (CHG 4% hand scrub plus Et 70%/CHG 3% rub), demonstrating that the inclusion of PS confers a notable residual effect. We speculate that this non-volatile ingredient acts synergistically with CHG. This promising combination represents an alternative method for the development of new disinfection strategies.

3Y-TZP/Ta Biocermet as a Dental Material: An Analysis of the In Vitro Adherence of Streptococcus Oralis Biofilm and an In Vivo Pilot Study in Dogs.

The surface adhesion of bacterial cells and the in vivo biocompatibility of a new ceramic-metal composite made of zirconium dioxide and tantalum were evaluated. Within the framework of an in vitro study using the crystal violet staining and colony counting methods, a relatively similar adhesion of Streptococcus oralis to the 3Y-TZP/Ta biocermet (roughness Ra = 0.12 ± 0.04 µm) and Ti-Al6-V4 titanium alloy (Ra = 0.04 ± 0.01 µm) was found. In addition, in an in vivo preliminary study focused on the histological analysis of a series of rods implanted in the jaws of beagle dogs for a six-month period, the absence of any fibrous tissue or inflammatory reaction at the interface between the implanted 3Y-TZP/Ta biocermets and the new bone was found. Thus, it can be concluded that the developed ceramic-metal biocomposite may be a promising new material for use in dentistry.

Influence of the MBC/MIC ratio on the antibacterial activity of vancomycin versus linezolid against methicillin-resistant Staphylococcus aureus isolates in a pharmacodynamic model simulating serum and soft tissue interstitial fluid concentrations reported in diabetic patients.

OBJECTIVES: To explore serum and tissue pharmacodynamics of linezolid versus vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates with different MBC/MIC ratios. METHODS: Five strains (vancomycin MIC/MBCs, mg/L) were used: TOL-1 (2/≥64), TOL-2 (1/16), LT-1 and LT-2 (1/8) and NT (1/2). The linezolid MIC/MBC for all strains was 2/≥64 mg/L. A two-compartment dynamic computerized device was used (inocula 10(7) cfu/mL). Free concentrations obtained in serum and interstitial fluid with twice-daily regimens of 1 g of vancomycin or 600 mg of linezolid were simulated over 48 h. ABBCs (differences between control growth curves and killing curves of bacteria exposed to antibiotics; log10 cfu × h/mL) and log10 reductions in initial inocula were calculated. RESULTS: In serum simulations, vancomycin (AUC0-24/MIC = 251.8 for TOL-1 and 503.6 for the remaining strains) was bacteriostatic against strains with MBC/MIC ≥8, but bactericidal against NT. In interstitial fluid simulations (AUC0-24/MIC = 54.6 for TOL-1 and 109.2 for the remaining strains), initial inocula grew in all cases. Linezolid, both in serum (AUC0-24/MIC = 87.0) and in interstitial fluid (AUC0-24/MIC = 130.6) simulations, reduced initial inocula ≥2.2 log10 for all strains (apart from LT-1 in serum simulations that showed a bacteriostatic profile). ABBCs were similar in serum and interstitial fluid with linezolid, but significantly lower in interstitial fluid simulations with vancomycin. CONCLUSIONS: From the pharmacodynamic perspective (serum concentrations), vancomycin tolerance should include MBC/MIC ≥8 since strains exhibiting this ratio showed bacteriostatic profiles similar to those obtained with isolates with MBC/MIC ratios of 16 or 32. Insufficient concentrations of vancomycin at the simulated infected site were linked to bacteriological failure. Free concentrations of linezolid at the infection site pharmacodynamically covered MRSA.

Effect on the reduction of bacterial load after surgical hand antisepsis with triclosan 0.5% compared to triclosan 0.5% followed by 70% alcoholic solution.

Triclosan 0.5% by scrubbing does not meet the UNE-EN12791 criteria to be used in the surgical hand preparation (SHP). Triclosan 0.5% by scrubbing followed by ethanol 70% hand rubbing is suitable without the additional characteristic of sustained effect. This limited effectiveness implies that triclosan should be avoided in SHP given the restrictions on its use in consumer antiseptic products. The trial was registered at ClinicalTrials.gov (ID: NCT04538365).

Endogenous cannabinoid system regulates intestinal barrier function in vivo through cannabinoid type 1 receptor activation.

The deleterious effects of stress on the gastrointestinal tract seem to be mainly mediated by the induction of intestinal barrier dysfunction and subsequent subtle mucosal inflammation. Cannabinoid 1 receptor (CB1R) is expressed in the mammalian gut under physiological circumstances. The aim of this investigation is to study the possible role of CB1R in the maintenance of mucosal homeostasis after stress exposure. CB1R knockout mice (CB1R(-/-)) and their wild-type (WT) counterparts were exposed to immobilization and acoustic (IA) stress for 2 h per day during 4 consecutive days. Colonic protein expression of the inducible forms of the nitric oxide synthase and cyclooxygenase (NOS2 and COX2), IgA production, permeability to (51)Cr-EDTA, and bacterial translocation to mesenteric lymph nodes were evaluated. Stress exposure induced greater expression of proinflammatory enzymes NOS2 and COX2 in colonic mucosa of CB1R(-/-) mice when compared with WT animals. These changes were related with a greater degree of colonic barrier dysfunction in CB1R(-/-) animals determined by 1) a significantly lower IgA secretion, 2) higher paracellular permeability to (51)Cr-EDTA, and 3) higher bacterial translocation, both under basal conditions and after IA stress exposure. Pharmacological antagonism with rimonabant reproduced stress-induced increase of proinflammatory enzymes in the colon described in CB1R(-/-) mice. In conclusion, CB1R exerts a protective role in the colon in vivo through the regulation of intestinal secretion of IgA and paracellular permeability. Pharmacological modulation of cannabinoid system within the gastrointestinal tract might be therapeutically useful in conditions on which intestinal inflammation and barrier dysfunction takes place after exposure to stress.

In vitro interference of tigecycline at subinhibitory concentrations on biofilm development by Enterococcus faecalis.

OBJECTIVES: Since biofilm formation is the hallmark of Enterococcus faecalis isolates, the aim of this study was to quantify biofilm formation in the presence of subinhibitory concentrations of tigecycline. METHODS: Interference of tigecycline on biofilm formation was spectrophotometrically quantified using 20 biofilm-producing E. faecalis isolates with tigecycline MICs of 0.12 (8 strains) or 0.25 mg/L (12 strains). Biofilm production was measured in antibiotic-free tryptic soy broth supplemented with 1% glucose and compared with biofilm production in the same medium with tigecycline at subinhibitory concentrations (0.25× or 0.5× MIC, similar to trough concentrations in serum or concentrations in the colon after a standard dose) by reading the optical density at 450 nm (OD(450)) after staining with Crystal Violet. RESULTS: In the presence of subinhibitory tigecycline concentrations, pooled OD(450) values for the 20 strains [median (IQR)] were significantly lower than those for controls: 0.468 (0.379-0.516) for antibiotic-free controls versus 0.295 (0.200-0.395) for 0.25× MIC tigecycline (P < 0.001) and 0.287 (0.245-0.479) for 0.5× MIC tigecycline (P < 0.001), with significant differences between pooled OD(450) values obtained with each concentration of tigecycline (P = 0.022). In 17 out of 20 (85%) strains the OD(450) obtained with 0.25× MIC tigecycline was significantly (P < 0.05) lower than the basal OD(450), while this occurred in 12 out of 20 (60%) strains with 0.5× MIC. CONCLUSIONS: In vitro tigecycline subinhibitory concentrations were able to interfere with biofilm formation by E. faecalis.

Survival of human pathogenic bacteria in different types of natural mineral water.

The aim of this study was to determine the survival of human pathogens (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) in five natural mineral waters (NMWs) with different properties and mineralization levels. Five NMWs from four Spanish spas with different dry residue at 110 °C were used: A = 76,935 mg/L; B = 1,827 mg/L; C = 808.4 mg/L; D = 283.8 mg/L; and E = 170.4 mg/L. An initial inoculum of 1 × 10(6) colony forming units (cfu)/mL was used for survival studies. Distilled water, chlorinated tap water and Mueller-Hinton broth were used as controls. Colony counts in all different waters were lower than those achieved with Mueller-Hinton broth over all incubation periods. A direct effect between the bacterial survival and the level of mineralization water was observed. The NMW E with low mineralization level along with the radioactive properties showed the highest antibacterial activity among all NMWs.

Influence of Sexual Dimorphism, Aging, and Differential Cell Capture Efficiency of Blood Separation Systems on the Quality of Platelet-Rich Plasma.

Few studies have checked the impact of the hormonal/immunological dimorphism of patients on the cellular composition of platelet-rich plasma products (PRP). Whole blood (WB) from 26 volunteers was concentrated using a device previously characterized. Platelet and white blood cell (WBC) counts in WB and PRP were compared between genders, and after the population was split into pre (≤50 years)- and post (>50 years)-menopausal ages. In WB, platelet−total WBC densities were comparable in men and women. The phagocytic cell composition differed (p ≤ 0.04). After dividing by ages, phagocytic cell discrepancies were linked to women > 50 years (p ≤ 0.05), and differences emerged in lymphocyte counts (lower in >50 years groups, within and between genders, p ≤ 0.05). In PRP, densities were significantly higher, but the PRP/WB ratios varied according to blood cell (lower for phagocytic cells) and between subjects (more favorable at a lower density of a particular blood cell in WB). This "system compensatory efficiency" reduced/reverted PRP differences in the leukocyte composition between genders/age−sex groups in WB. In PRP, neutrophils were higher in younger men than older women (p < 0.05). WB lymphocyte differences between age−sex groups persisted. Age is a more determining factor than sex in the preparation of PRP. Post-menopause, sexual dimorphism strongly influences the composition of leukocytes, also conditioned by the capture efficiency of the system.

Innovative Medial Cushioning Orthoses Affect Peroneus Longus Electromyographic Activity during Running.

Background: Over-supination processes of the foot and ankle involving peroneus longus (PL) damage during running sports have been treated conservatively with passive control tools, such as tapes, braces, or external ankle supports, but the effect of orthoses with typical lateral wedging orthoses (TLWO) on the muscular activity of PL during running remains unclear. Here we investigate the effects of innovative medial cushioning orthoses (IMCO) on PL activity during the full running gait cycle. In addition, we wished to ascertain the effects of innovative medial cushioning orthoses (IMCO) on PL activity during running. Methods: Thirty-one healthy recreational runners (mean age 34.5 ± 3.33) with neutral foot posture index scores, were selected to participate in the present study. They ran on a treadmill at 9 km/h wearing seven different orthoses (NRS, IMCO 3 mm, IMCO 6 mm, IMCO 9 mm, TLWO 3 mm, TLWO 6 mm and TLWO 9 mm), randomly performed on the same day while electromyographic activity of the PL muscle was recorded. Statistical intraclass correlation coefficient (ICC) to test reliability was carried out and the Wilcoxon test with Bonferroni's correction was developed to analyze the differences between the conditions. Results: the reliability of all assessments showed data higher than 0.81, that is, "almost perfect reliability"; all EMG PL values wearing either TLWO or IMCO showed a statistically significant reduction versus NRS during the fully analyzed running gait cycle; the highest difference was set on NRS 23.08 ± 6.67 to TLWO 9 mm 17.77 ± 4.794 (p < 0.001). Conclusions: Muscular EMG activity of the PL during the full running gait cycle decreases when wearing either TLWO or IMCO relative to NRS; therefore, these orthoses could be prescribed to treat the strain and overload pathologies of PL. In addition, IMCO­as it less thick, compared with TLWO­can be used when aiming to achieve better running economy.

Efficacy of simulated cefditoren versus amoxicillin-clavulanate free concentrations in countering intrastrain ftsI gene diffusion in Haemophilus influenzae.

This study explores the effects of cefditoren (CDN) versus amoxicillin-clavulanic acid (AMC) on the evolution (within a single strain) of total and recombined populations derived from intrastrain ftsI gene diffusion in ß-lactamase-positive (BL⁺) and ß-lactamase-negative (BL⁻) Haemophilus influenzae. DNA from ß-lactamase-negative, ampicillin-resistant (BLNAR) isolates (DNA(BLNAR)) and from ß-lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) (DNA(BLPACR)) isolates was extracted and added to a 107-CFU/ml suspension of one BL⁺ strain (CDN MIC, 0.007 µg/ml; AMC MIC, 1 µg/ml) or one BL⁻ strain (CDN MIC, 0.015 µg/ml; AMC MIC, 0.5 µg/ml) in Haemophilus Test Medium (HTM). The mixture was incubated for 3 h and was then inoculated into a two-compartment computerized device simulating free concentrations of CDN (400 mg twice a day [b.i.d.]) or AMC (875 and 125 mg three times a day [t.i.d.]) in serum over 24 h. Controls were antibiotic-free simulations. Colony counts were performed; the total population and the recombined population were differentiated; and postsimulation MICs were determined. At time zero, the recombined population was 0.00095% of the total population. In controls, the BL⁻ and BL⁺ total populations and the BL⁻ recombined population increased (from ≈3 log10 to 4.5 to 5 log10), while the BL⁺ recombined population was maintained in simulations with DNA(BLPACR) and was decreased by ≈2 log10 with DNA(BLNAR). CDN was bactericidal (percentage of the dosing interval for which experimental antibiotic concentrations exceeded the MIC [ft>MIC], >88%), and no recombined populations were detected from 4 h on. AMC was bactericidal against BL⁻ strains (ft>MIC, 74.0%) in DNA(BLNAR) and DNA(BLPACR) simulations, with a small final recombined population (MIC, 4 µg/ml; ft>MIC, 30.7%) in DNA(BLPACR) simulations. When AMC was used against the BL⁺ strain (in DNA(BLNAR) or DNA(BLPACR) simulations), the bacterial load was reduced ≈2 log10 (ft>MIC, 44.3%), but 6.3% and 32% of the total population corresponded to a recombined population (MIC, 16 µg/ml; ft>MIC, 0%) in DNA(BLNAR) and DNA(BLPACR) simulations, respectively. AMC, but not CDN, unmasked BL⁺ recombined populations obtained by transformation. ft>MIC values higher than those classically considered for bacteriological response are needed to counter intrastrain ftsI gene diffusion by covering recombined populations.

Comparing rubbing and scrubbing surgical hand antisepsis with propan-1-ol 60% in accordance with European regulation UNE-EN 12791:2016+A1:2018.

A crossover trial was conducted to compare hand rub and hand scrub-brush methods for reducing bacterial loads when using propan-1-ol-60% according to European regulations. Both methods significantly reduced the bacterial load immediately after antisepsis, but only the hand rub method achieved significant bacterial load reduction 3 hours after the procedure.

Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains.

Antibiotic resistance in Streptococcus pneumoniae has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin (12.5 to 50 mg/kg) or seconeolitsine (5 to 40 mg/kg) were administered every 12 h during two days in mice infected with a serotype 8-resistant strain. At 48 h, a 70% protection was obtained with seconeolitsine (40 mg/kg; p < 0.001). However, survival with levofloxacin was 20%, regardless of the dose. In addition, seconeolitsine decreased bacteremia efficiently. Levofloxacin had higher levels in serum than seconeolitsine (Cmax of 14.7 vs. 1.6; p < 0.01) and higher values of area under the serum concentration-time curve (AUC0-12h of 17.3 vs. 5; p < 0.01). However, seconeolitsine showed higher levels of time to peak concentration and elimination half-life. This is consistent with the higher binding of seconeolitsine to plasma proteins (40% and 80% when used at 1 µg/mL and 50 µg/mL, respectively) in comparison to levofloxacin (12% at 5 µg/mL and 33% at 50 µg/mL). Our results suggest that seconeolitsine would be a promising therapeutic alternative against pneumococcal isolates with high fluoroquinolone resistance levels.

Commercial blood cell separation systems versus tube centrifugation methods for the preparation of platelet-rich plasma: a preliminary cross-sectional study.

OBJECTIVE: Clinical studies claim that platelet-rich plasma (PRP) accelerates tissue healing due to its high concentration of growth factors and that the combination with leukocytes improves the antimicrobial effect of the concentrate. Most of these studies obtained PRP using different separation systems, and few analyzed the content of the PRP used for treatment. This study characterized the composition of PRP and white blood cells (WBC) from a single donor produced by three commercially available PRP separation systems and two anticoagulated general analytical tubes. METHODS: Five patients donated 50 mL of blood, which was processed to produce PRP and WBC using three PRP concentration systems (i.e., Easy PRP Kit, GloPRP, and Wego) and two tubes for general analysis anticoagulated with ethylenediaminetetraacetic acid (EDTA) and citrate. Platelets and WBC in combination with their concentrates were analyzed by automated systems in a clinical laboratory. RESULTS: There were no significant differences in the average concentrations of PRP platelets and WBC between GloPRP and the tubes for general analysis with EDTA and citrate; however, the Easy PRP Kit gave results much superior to the rest of the methods, especially comparing it with the Wego Kit, whose concentrates were especially low, even nonexistent for WBC. CONCLUSIONS: The Easy PRP Kit concentrates WBC-rich PRP, resulting in increased WBC concentrations, compared with low WBC-low PRP of GloPRP and general tube methods for EDTA and citrate analysis and the even lower concentration of PRP from the Wego Kit, with the absence of leukocytes.

Genotypic versus phenotypic characterization, with respect to beta-lactam susceptibility, of Haemophilus influenzae isolates exhibiting decreased susceptibility to beta-lactam resistance markers.

Among 165 Spanish Haemophilus influenzae isolates with mutations in the ftsI gene (ftsI(+)) (2005 to 2007), 73% were beta-lactamase negative and 26.7% were positive. The proportion of beta-lactamase-negative isolates to beta-lactamase-positive isolates was 2:1 to 4:1 in general, versus 1:3 in pediatric hospitals. Among 44 beta-lactamase-positive strains, 8 strains produced ROB-1 (5 from the pediatric hospital). beta-Lactamase-positive ftsI(+) strains were phylogenetically closer than were beta-lactamase-negative strains.

Influence of different resistance traits on the competitive growth of Haemophilus influenzae in antibiotic-free medium and selection of resistant populations by different {beta}-lactams: an in vitro pharmacodynamic approach.

OBJECTIVES: The aim was to study the pharmacodynamics of cefditoren, amoxicillin/clavulanic acid and cefuroxime against mixed Haemophilus influenzae strains. METHODS: Isolates [MICs (mg/L) of cefditoren, cefuroxime and amoxicillin/clavulanic acid] used were: one beta-lactamase-negative (beta(-); 0.015, 1 and 1), one beta-lactamase-positive (beta(+); 0.03, 4 and 8) and two strains exhibiting ftsI gene mutations [one beta(-) ampicillin-resistant (BLNAR; 0.015, 8 and 4) and one beta(+) amoxicillin/clavulanic acid-resistant (BLPACR; 0.03, 8 and 4)]. A computerized pharmacodynamic model simulating free antibiotic concentrations (calculated considering reported percentages of protein binding) of 400 mg twice-daily cefditoren, 500 mg twice-daily cefuroxime and 875/125 mg three times daily amoxicillin/clavulanic acid was used to explore antibacterial activity against initial mixed inocula with 25% of each strain. Areas under bacterial curves (AUBCs) from 0 to 24 h (log cfu.h/mL) were calculated and differences between values in antibiotic-free (AUBC(K)) and in antibiotic simulations determined (ABBC(0-24) = AUBC(K0-24)-AUBC(0-24)). RESULTS: In antibiotic-free medium, total population increased by 1.7 log(10) cfu/mL from 0 to 24 h: final composition approximately 90% beta(-), approximately 6.5% beta(+), approximately 2.5% BLNAR and approximately 1% BLPACR. At the end of antibiotic simulations, the predominant population was BLPACR followed by beta(+) after amoxicillin/clavulanic acid or BLNAR after cefuroxime exposures. ABBC(0-24) was higher (P < 0.01) for cefditoren compared with cefuroxime or amoxicillin/clavulanic acid whether considering total population (70.4 versus approximately 33), beta(+) (77.8 versus approximately 52), BLNAR (66.1 versus 18.6-30.4) or BLPACR (40.8 versus approximately 0). CONCLUSIONS: Cefditoren offered higher antibacterial effect than cefuroxime and amoxicillin/clavulanic acid against a mixed population of H. influenzae strains due to its higher activity against beta-lactamase-producing strains and those carrying ftsI gene mutations.

In vitro effect of physiological concentrations of human albumin on the antibacterial activity of tigecycline.

OBJECTIVES: To determine C(max) tigecycline activity in the presence/absence of physiological concentrations of human albumin with free fraction concentrations as controls. METHODS: Killing curves (final inoculum: 1.0-5.0 x 10(7) cfu/mL) were performed with 0.88 mg/L final concentrations (serum C(max) after a 100 mg 1 h infusion) in Mueller-Hinton broth supplemented with Ca(2+) and Mg(2+) (MH) and in MH with 4 g/dL human albumin. Controls were curves in MH with concentrations similar to the free fraction (fC(max) = 0.17 mg/L) calculated using protein binding. Activity was measured as log(10) initial inoculum reduction (log(10) initial inoculum-log(10) at 12 h/24 h). Target strains (tigecycline MIC/MBC; mg/L) were: methicillin-resistant Staphylococcus aureus heteroresistant to vancomycin (0.12/0.25); Enterococcus faecium (0.12/0.25); Escherichia coli producing extended-spectrum beta-lactamase (0.12/0.25); and Acinetobacter baumannii (0.25/1). RESULTS: At 24 h the fC(max) produced mean decreases of < or =0.1 cfu/mL for all strains, in contrast to the bactericidal activity (mean >3 log(10) reduction) provided by C(max) concentrations in the presence or absence of albumin for E. coli and E. faecium, and an activity nearly bactericidal for S. aureus (mean approximately 2.8 log(10) reduction). In the case of the A. baumannii isolate the C(max) in the presence or absence of albumin produced a mean reduction of 2.56 log(10) cfu/mL at 12 h (time of one dosing interval), with a bacteriostatic profile when considering 24 h colony counts (similar counts at 0 and 24 h). CONCLUSIONS: Correcting the total concentration for the reported literature binding values is unreliable since tigecycline antibacterial activity was greater than that suggested by the free fraction of the drug.