Discovery of Gambogic acid as an antibacterial adjuvant against vancomycin-resistant enterococci in vitro and in vivo.

BACKGROUND: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.f. (Clusiaceae), which possesses antibacterial activity. PURPOSE: This study aimed to investigate the potential of GA as an adjuvant to restore the susceptibility of VRE to vancomycin. METHODS: In vitro antibacterial and synergistic activities were evaluated against vancomycin-susceptible and resistant strains by the broth microdilution method for the Minimal Inhibitory Concentrations (MICs) determination, and checkerboard assay and time-kill curve analysis for synergy evaluation. In vivo study was conducted on a mouse multi-organ infection model. The underlying antibacterial mechanism of GA was also explored. RESULTS: GA showed a potent in vitro activity against all tested strains, with MICs ranging from 2 to 4 µg/ml. The combination of GA and vancomycin exhibited a synergistic effect against 18 out of 23 tested VRE strains, with a median fractional inhibitory concentration index (FICI) of 0.254, and demonstrated a synergistic effect in the time-kill assay. The combination therapy exhibited a significant reduction in tissue bacterial load compared with either compound used alone. GA strongly binds to the ParE subunit of topoisomerase IV, a bacterial type II DNA topoisomerase, and suppresses its activity. CONCLUSIONS: The study suggests that GA has a significant antibacterial activity against enterococci, and sub-MIC concentrations of GA can restore the activity of vancomycin against VRE in vitro and in vivo. These findings indicate that GA has the potential to be a new antibacterial adjuvant to vancomycin in the treatment of infections caused by VRE.

Risk factors for mortality after linezolid treatment of vancomycin-resistant Enterococcus bloodstream infection.

OBJECTIVES: We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). METHODS: We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. RESULTS: A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. CONCLUSION: The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.

Aminopenicillins for treatment of ampicillin-resistant enterococcal urinary tract infections.

PURPOSE: The purpose of this review is to describe the theory behind and data supporting use of aminopenicillins in the treatment of ampicillin-resistant enterococcal urinary tract infections. SUMMARY: Aminopenicillin concentrations in the urine may be high enough to achieve bacterial eradication and clinical cure for infections affecting the lower genitourinary tract, even in the context of in vitro resistance based on established susceptibility breakpoints. A literature search was conducted to identify original research articles describing the use of aminopenicillins in the treatment of urinary tract infections caused by ampicillin-resistant Enterococcus species. Three published retrospective cohort studies were identified, all of which reported that aminopenicillins had similar rates of clinical cure as other antibiotic classes prescribed for the treatment of enterococcal urinary tract infections. CONCLUSION: Both pharmacokinetic/pharmacodynamic principles and limited retrospective clinical data support the use of aminopenicillins in the treatment of lower urinary tract infections caused by Enterococcus species, even when the isolates have a minimum inhibitory concentration that exceeds the susceptibility breakpoint.

Daptomycin susceptibility testing and therapeutic use in enterococcal bloodstream infection (EBSI) in a setting with high rates of vancomycin-resistant Enterococcus faecium (VREfm).

BACKGROUND: There is in vitro and clinical evidence to suggest daptomycin has good activity against Enterococcus. In 2019, CLSI produced clinical breakpoints for Enterococcus spp. OBJECTIVES: To describe the distribution of MICs of daptomycin for enterococcal bloodstream infection (EBSI) isolates in a large Scottish health board, the indications for local daptomycin susceptibility testing and daptomycin doses used in vancomycin-resistant Enterococcus faecium (VREfm) infection. METHODS: We investigated all EBSIs over a 21 month period and identified isolates tested against daptomycin. We recorded the distribution of MICs, as well as indications for daptomycin susceptibility testing and information on daptomycin dosing, where it was used. RESULTS: There were 293 blood culture isolates of Enterococcus spp., of which 37 had daptomycin susceptibility testing performed, from 31 individual patients. Of the 293 isolates, 103 were E. faecium, of which 63 were VREfm. Daptomycin testing was indicated by vancomycin resistance in 24/37 isolates. All E. faecium isolates tested were in the CLSI 'susceptible dose-dependent (SDD)' range of MICs. All other Enterococcus spp. tested were in the 'susceptible' range. Twelve patients received daptomycin, and dosing information was recovered for 10. Nine of these patients received 8-12 mg/kg/day dosing. There were no recorded adverse drug reactions. Ten of 12 patients were alive at the time of data collection. CONCLUSIONS: Daptomycin MIC distribution for EBSI isolates suggests a high local rate of susceptibility, according to CLSI breakpoints, in a population with high rates of VREfm. CLSI-recommended doses of daptomycin were used, with encouraging survival outcomes.

The Mechanism of Action of Ginkgolic Acid (15:1) against Gram-Positive Bacteria Involves Cross Talk with Iron Homeostasis.

With the increasing reports of community-acquired and nosocomial infection caused by multidrug-resistant Gram-positive pathogens, there is an urgent need to develop new antimicrobial agents with novel antibacterial mechanisms. Here, we investigated the antibacterial activity of the natural product ginkgolic acid (GA) (15:1), derived from Ginkgo biloba, and its potential mode of action against the Gram-positive bacteria Enterococcus faecalis and Staphylococcus aureus. The MIC values of GA (15:1) against clinical E. faecalis and S. aureus isolates from China were ≤4 and ≤8 µg/mL, respectively, from our test results. Moreover, GA (15:1) displayed high efficiency in biofilm formation inhibition and bactericidal activity against E. faecalis and S. aureus. During its inhibition of the planktonic bacteria, the antibacterial activity of GA (15:1) was significantly improved under the condition of abolishing iron homeostasis. When iron homeostasis was abolished, inhibition of planktonic bacteria by GA (15:1) was significantly improved. This phenomenon can be interpreted as showing that iron homeostasis disruption facilitated the disruption of the functions of ribosome and protein synthesis by GA (15:1), resulting in inhibition of bacterial growth and cell death. Genetic mutation of ferric uptake regulator (Fur) led to GA (15:1) tolerance in in vitro-induced resistant derivatives, while overexpression of Fur led to increased GA (15:1) susceptibility. Additionally, GA (15:1) significantly decreased the bacterial loads of S. aureus strain USA300 in the lung tissues of mice in a pneumonic murine model. Conclusively, this study revealed an antimicrobial mechanism of GA (15:1) involving cross talk with iron homeostasis against Gram-positive pathogens. In the future, the natural product GA (15:1) might be applied to combat infections caused by Gram-positive pathogens. IMPORTANCE The increasing emergence of infectious diseases associated with multidrug-resistant Gram-positive pathogens has raised the urgent need to develop novel antibiotics. GA (15:1) is a natural product derived from Ginkgo biloba and possesses a wide range of bioactivities, including antimicrobial activity. However, its antibacterial mechanisms remain unclear. Our current study found that the function of ferric uptake regulator (Fur) was highly correlated with the antimicrobial activity of GA (15:1) against E. faecalis and that the antibacterial activity of GA (15:1) could be strengthened by the disruption of iron homeostasis. This study provided important insight into the mode of action of GA (15:1) against Gram-positive bacteria and suggested that GA (15:1) holds the potential to be an antimicrobial treatment option for infection caused by multidrug-resistant Gram-positive pathogens.

Prevalence and antimicrobial susceptibility pattern of urinary tract infection among pregnant women attending Hargeisa Group Hospital, Hargeisa, Somaliland.

The aim of this study was to determine the prevalence, antimicrobial susceptibility pattern and associated factors of urinary tract infection (UTI) among pregnant women attending Hargeisa Group Hospital (HGH), Hargeisa, Somaliland. A cross-sectional study was conducted at HGH, Hargeisa, Somaliland and participants were selected by systematic random sampling technique. Clean catch midstream urine samples were collected from 422 participants and cultured and antimicrobial susceptibility pattern was determined for the isolates. Univariable and multivariable logistic regression analyses were utilized to identify the independent risk factors for UTI. The prevalence of UTI was 16.4% (95% CI 13.3-19.9). The predominant bacteria isolate was E. coli (43.5%) followed by Coagulase negative staphylococcus (CoNS) 11(16%), S. aureus 9(13%), K. pneumonia 6(8.7%), Pseudomonas aeruginosa 5(7.2%), Proteus mirabilis 4(5.8%), Citrobacter spp 3(4.4%) and M. morganii 1(1.5%) Gram negative bacilli were resistant to ampicillin (96%) and tetracycline (71.4%) and Gram-positive cocci were also resistant to ampicillin (90%), tetracycline (55%). Multidrug resistance was observed in 85.5% of bacterial isolated. No formal education participants, previous history of catheterization and previous history of UTI had 3.18, 3.22 and 3.73 times respectively more likely to develop UTI than their counterparts. Culture and susceptibility test is vital for appropriate management of UTI in the study area.

Combination therapy for disseminated strongyloidiasis with associated vancomycin-resistant, linezolid-intermediate Enterococcus faecium meningitis: A case report.

WHAT IS KNOWN AND OBJECTIVE: The rhabditid nematode Strongyloides stercoralis is the major causative agent of disseminated strongyloidiasis (DS). In rare cases, DS has caused enterococcal meningitis. If DS-associated vancomycin-resistant Enterococcus faecium (VRE) meningitis is suspected, combination antibiotic therapy should be considered. CASE SUMMARY: We present a case of a 61-year-old male who developed DS associated with vancomycin-resistant and linezolid-intermediate E. faecium meningitis after receiving corticosteroids. The VRE meningitis was treated with high-dose daptomycin 12 mg/kg, linezolid, tigecycline and quinupristin/dalfopristin. Despite negative cultures, the patient expired. WHAT IS NEW AND CONCLUSION: In patients with DS-associated VRE meningitis, early use of combination therapy may be warranted to improve patient outcomes.

[Enterococcal infections and their treatment options].

AIM: The study aimed to characterize enterococcal infections at the University Hospital Olomouc and to define antibiotic treatment options. MATERIAL AND METHODS: The data was obtained from the ENVIS LIMS laboratory information system. Between 1 January 2015 and 31 December 2019, clinically relevant enterococci in the hospital and their resistance to antibiotics were retrospectively evaluated. Until mid-2016, criteria defined by Facklam and Collins and biochemical properties determined with the Encoccus test were used for identification. Subsequently, all enterococci were identified using the MALDI-TOF MS system. The susceptibility to antibiotics was determined using a standard microdilution method according to the EUCAST criteria. RESULTS: A total of 8 239 clinically relevant enterococci were isolated over the 5-year period. The most frequently isolated species were Enterococcus faecalis and Enterococcus faecium, which accounted for more than 90% in the period 2017-2019. Enterococci were most frequently isolated from urine (35 %), surgical wounds (17 %) and urethral/vaginal swabs (17 %). Clinically relevant enterococci were most commonly isolated from patients with oncological diagnoses (22%), those with urinary and genital diseases (15%) and respiratory diseases (9%). Enterococcus faecalis strains showed very low resistance to the antibiotics tested. Enterococcus faecium was shown to have 24 % proportion of vancomycin-resistant strains (VRE). CONCLUSION: Primary antibiotics suitable for treating infections with the etiological role of Enterococcus faecalis include aminopenicillins, in case of severe infections in combination with aminoglycosides, in particular gentamicin. For Enterococcus faecium strains, glycopeptides must be chosen. To treat VRE, linezolid or tigecycline are indicated.

Surgical Site Infections and Antimicrobial Resistance After Cesarean Section Delivery in Rural Rwanda.

Background: As the volume of surgical cases in low- and middle-income countries (LMICs) increases, surgical-site infections (SSIs) are becoming more prevalent with anecdotal evidence of antimicrobial resistance (AMR), despite a paucity of data on resistance patterns. Objectives: As a primary objective, this prospective study aimed to describe the epidemiology of SSIs and the associated AMR among women who delivered by cesarean at a rural Rwandan hospital. As secondary objectives, this study also assessed patient demographics, pre- and post-operative antibiotic use, and SSI treatment. Methods: Women who underwent cesarean deliveries at Kirehe District Hospital between September 23rd, 2019, and March 16th, 2020, were enrolled prospectively. On postoperative day (POD) 11 (+/- 3 days), their wounds were examined. When an SSI was diagnosed, a wound swab was collected and sent to the Rwandan National Reference Laboratory for culturing and antibiotic susceptibility testing. Findings: Nine hundred thirty women were enrolled, of whom 795 (85.5%) returned for the POD 11 clinic visit. 45 (5.7%) of the 795 were diagnosed with SSI and swabs were collected from 44 of these 45 women. From these 44 swabs, 57 potential pathogens were isolated. The most prevalent bacteria were coagulase-negative staphylococci (n = 12/57, 20.3% of all isolates), and Acinetobacter baumannii complex (n = 9/57, 15.2%). 68.4% (n = 39) of isolates were gram negative; 86.7% if excluding coagulase-negative staphylococci. No gram-negative pathogens isolated were susceptible to ampicillin, and the vast majority demonstrated intermediate susceptibility or resistance to ceftriaxone (92.1%) and cefepime (84.6%). Conclusions: Bacterial isolates from SSI swab cultures in rural Rwanda predominantly consisted of gram-negative pathogens and were largely resistant to commonly used antibiotics. This raises concerns about the effectiveness of antibiotics currently used for surgical prophylaxis and treatment and may guide the appropriate selection of treatment of SSIs in rural Rwanda and comparable settings.

Antimicrobial susceptibility testing of Eggerthella lenta blood culture isolates at a university hospital in Belgium from 2004 to 2018.

OBJECTIVES: Eggerthella lenta is a Gram-positive anaerobic bacillus that is an important cause of bloodstream infections. This study aims to test the susceptibility of Eggerthella lenta blood culture isolates to commonly used antibiotics for the empirical treatment of anaerobic infections. METHODS: In total, 49 positive blood cultures for Eggerthella lenta were retrospectively included from patients hospitalised at the Universitair Ziekenhuis Brussel, Belgium, between 2004 and 2018. Identification was done by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Antimicrobial susceptibility testing was performed using the reference agar dilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines with Brucella agar supplemented with 5 µg/mL hemin, 1 µg/mL vitamin K1 and 5% laked sheep blood. The minimal inhibitory concentrations were interpreted using the EUCAST breakpoints. Clinical characteristics were collected by reviewing the patient's medical records. RESULTS: All isolates were susceptible to amoxicillin-clavulanate, metronidazole and meropenem. Eighty-eight % of them were susceptible to clindamycin and 94% (20% S, 74% I) were susceptible to piperacillin-tazobactam. The mean age of the patients was 64 (±20) and they showed a 30-day mortality of 27%. The source of infection was in 65.3% of the cases abdominal, 20.4% were sacral pressure ulcers and 14.3% were unknown causes. While all isolates were fully susceptible at standard dosing regimen to amoxicillin-clavulanate, most were only susceptible at increased exposure or resistant to piperacillin-tazobactam. CONCLUSIONS: Our results suggest to be careful with the use of piperacillin-tazobactam and clindamycin in the empirical treatment of Eggerthella lenta infections.

Suppressive Effect of Two Cucurbitane-Type Triterpenoids from Momordica charantia on Cutibacterium acnes-Induced Inflammatory Responses in Human THP-1 Monocytic Cell and Mouse Models.

Cutibacterium acnes (formerly Propionibacterium acnes) is one of the major bacterial species responsible for acne vulgaris. Numerous bioactive compounds from Momordica charantia Linn. var. abbreviata Ser. have been isolated and examined for many years. In this study, we evaluated the suppressive effect of two cucurbitane-type triterpenoids, 5ß,19-epoxycucurbita-6,23-dien-3ß,19,25-triol (Kuguacin R; KR) and 3ß,7ß,25-trihydroxycucurbita-5,23-dien-19-al (TCD) on live C. acnes-stimulated in vitro and in vivo inflammatory responses. Using human THP-1 monocytes, KR or TCD suppressed C. acnes-induced production of interleukin (IL)-1ß, IL-6 and IL-8 at least above 56% or 45%, as well as gene expression of these three pro-inflammatory cytokines. However, a significantly strong inhibitory effect on production and expression of tumor necrosis factor (TNF)-α was not observed. Both cucurbitanes inhibited C. acnes-induced activation of the myeloid differentiation primary response 88 (MyD88) (up to 62%) and mitogen-activated protein kinases (MAPK) (at least 36%). Furthermore, TCD suppressed the expression of pro-caspase-1 and cleaved caspase-1 (p10). In a separate study, KR or TCD decreased C. acnes-stimulated mouse ear edema by ear thickness (20% or 14%), and reduced IL-1ß-expressing leukocytes and neutrophils in mouse ears. We demonstrated that KR and TCD are potential anti-inflammatory agents for modulating C. acnes-induced inflammation in vitro and in vivo.

Lubeluzole: from anti-ischemic drug to preclinical antidiarrheal studies.

BACKGROUND: Lubeluzole, a neuroprotective anti-ischemic drug, was tested for its ability to act as both antibiotic chemosensitizing and antipropulsive agent for the treatment of infectious diarrhea. METHODS: In the present report, the effect of lubeluzole against antidiarrheal target was tested. The antimicrobial activity towards Gram-positive and Gram-negative bacteria was investigated together with its ability to affect ileum and colon contractility. RESULTS: Concerning the antimicrobial activity, lubeluzole showed synergistic effects when used in combination with minocycline against four common Gram-positive and Gram-negative bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922), although relatively high doses of lubeluzole were required. In ex vivo experiments on sections of gut smooth muscles, lubeluzole reduced the intestinal contractility in a dose-dependent manner, with greater effects observed on colon than on ileum, and being more potent than reference compounds otilonium bromide and loperamide. CONCLUSION: All above results identify lubeluzole as a possible starting compound for the development of a novel class of antibacterial adjuvants endowed with spasmolytic activity.

Realgar increases defenses against infection by Enterococcus faecalis in Caenorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar has been used in traditional remedies for a long history in China and India. It is clinically used to treat diverse cancers, especially acute promyelocytic leukemia (APL), chronic myelogenous leukemia (CML) in China. However, paradoxic roles of realgar to increase or decrease immunity are reported. It is urgent to address this question, due to immune depression can be strongly benefit to cancer development, but detrimental to patients. AIM OF THE STUDY: This present work is to explore whether realgar promote or suppress immune responses, and shed light on its mode of action. Our results should provide cues for rational strategy to explore realgar for clinical use. MATERIAL AND METHODS: Infection model in vivo was established by using Enterococcus faecalis to attack Caenorhabditis elegans, then realgar was used to treat the infected worms to investigate its effects on infectivity and the underlying mechanism. Killing analysis was carried out to test whether realgar can mitigate worm infection. Thermotolerance resistance analysis was used to evaluate if realgar functions hormetic effect. Quantification of live E. faecalis in nematode intestine was employed to ascertain if realgar alleviate the bacterial load in worm gut. Quantitative real-time PCR (qRT-PCR) was used to test the expression of antibacterial effectors. Western blot was used to test the effect of realgar on the expressions of p38 and phospho-p38 in worms infected by E. faecalis. RESULTS: Realgar alleviated the infected worms in strains of N2, glp-4, and daf-2, but failed in sek-1, glp-4; sek-1, and daf-2; daf-16 when p38 MAPK or daf-16 was blocked or inactivated. Western blot assay demonstrated that realgar increased the expression of phosph-p38. Thermotolerance assay showed that realgar played a hormetic role on nemtodes, triggered protective response and reduced bacterial load after realgar treatment for 120 h qRT-PCR demonstrated that realgar significantly increased antibacterial effectors, thus leading to pathogen elimination. CONCLUSION: Realgar increased defenses against E. faecalis in C. elegans by inducing both immune responses and protective responses. It was regulated by p38 MAPK pathway and DAF-16.

Management and treatment of Aerococcus bacteremia and endocarditis.

OBJECTIVES: We describe our multicenter experience on diagnosis and management of Aerococcus bacteremia including the susceptibility profile of Aerococcus species and a suggested algorithm for clinicians. METHODS: Retrospective study of all patients with positive blood cultures for Aerococcus species from January 2005 to July 2020 in our institution with clinical data and susceptibility profile. Data were collected from both electronic health record and clinical microbiology laboratory database. RESULTS: There were 219 unique isolates with only the susceptibility profiles available, while 81 patients had clinical information available. Forty-nine of those cases were deemed as true bloodstream infection and the rest were of unclear clinical significance. Cases of endocarditis (n = 7) were high-grade, monomicrobial bacteremia caused by Aerococcus urinae. Patients with endocarditis were younger (66 vs 80 p < 0.05). The risk for endocarditis was higher if duration of symptoms was longer than 7 days (OR 105, 95% CI: 5-2271), or if there were septic emboli (OR 71, 95% CI: 3-1612). A DENOVA score cutoff of ≥ 3 was 100% sensitive and 89% specific in detecting endocarditis. The 30-day and 3-month all-cause mortality for bacteremia was 17% and 24%, respectively. Six out of seven patients with endocarditis survived. CONCLUSIONS: Antibiotic regimen for aerococcal bloodstream infections and endocarditis should be guided by species identification and antimicrobial susceptibility testing. DENOVA scoring system's performance in this study is more congruent to other studies. Hence, it can be used as an adjunctive tool in assessing the need for echocardiogram to rule out endocarditis. In our experience, two and four weeks of treatment for bloodstream infections and endocarditis, respectively, had good outcomes.

Increasing relevance of Gram-positive cocci in urinary tract infections: a 10-year analysis of their prevalence and resistance trends.

Urinary tract infections (UTIs) are the third most common types of infection in human medicine worldwide. There is increasing appreciation for the pathogenic role of Gram-positive cocci (GPC) in UTIs, as they have a plethora of virulence factors, maintaining their pathogenicity and high affinity for the epithelial cells of the urinary tract. The study was carried out using microbiological data collected corresponding to the period between 2008 and 2017. Antimicrobial susceptibility testing was performed using the disk diffusion method and E-tests. The age range of patients affected from the outpatient and inpatient groups differed significantly (43 [range 0.7-99] vs. 68 [range 0.4-99] years; p = 0.008). 3962 GPCs were obtained from inpatient and 4358 from outpatient samples, corresponding to 20.5 ± 2.8% (range 17.5-26.8%) and 20.6 ± 2.6% (range 17.8-26.0%) of all positive urine samples (p > 0.05); in both groups, Enterococcus spp. were the most prevalent (outpatients: 79.6%; inpatients: 88.5%). High-level aminoglycoside resistance in enterococci was noted in 31.0-46.6% of cases. A pronounced increase in the number of MRSA was seen in the second half of the study period (0.6-1.9% vs. 9.8-11.6%; p = 0.038). The ratio of VRE isolates was 0.16%, no VISA/VRSA isolates were detected.

Antimicrobial Activity of Schinopsis brasiliensis Engler Extract-Loaded Chitosan Microparticles in Oral Infectious Disease.

Enterococcus faecalis infections represent a health concern, mainly in oral diseases, in which treatments with chlorhexidine solution (0.2%) are often used; however, it presents high toxicity degree and several side effects. Based on this, the use of natural products as an alternative to treatment has been explored. Nonetheless, plant extracts have poor organoleptic characteristics that impair theirs in natura use. Therefore, this work aimed to evaluate the analytical profile, biological activity, and cytotoxicity in vitro of S. brasiliensis-loaded chitosan microparticles (CMSb) produced using different aspersion flow rates. The analytical fingerprint was obtained by FTIR and NIR spectra. Principal components analysis (PCA) was used to verify the similarity between the samples. The crystallinity degree was evaluated by X-ray diffraction (XRD). Phytochemical screening (PS) was performed to quantify phytocompounds. Antimicrobial activity was evaluated by minimum inhibitory concentration (MIC). Antibiofilm activity and bactericidal kinetics against E. faecalis (ATCC 29212 and MB 146-clinical isolated) were also assessed. The hemolytic potential was performed to evaluate the cytotoxicity. Data provided by FTIR, NIR, and PCA analyses revealed chemical similarity between all CMSb. Furthermore, the results from XRD analysis showed that the obtained CMSb present amorphous characteristic. Tannins and polyphenols were accurately quantified by the PS, but methodology limitations did not allow the flavonoid quantification. The low hemolytic potential assay indicates that all samples are safe. Antimicrobial assays revealed that CMSb were able to inhibit not only the E. faecalis ATCC growth but also the biofilm formation. Only one CMSb sample was able to inhibit the clinical strain. These results highlighted the CMSb antimicrobial potential and revealed this system as a promising product to treat infections caused by E. faecalis.

Reduced nephrotoxicity with vancomycin therapeutic drug monitoring guided by area under the concentration-time curve against a trough 15-20 µg/mL concentration.

Vancomycin is often employed as an antibacterial agent against Gram-positive bacteria, although dose-dependent nephrotoxicity is a concern. Although the risk may be reduced by therapeutic drug monitoring (TDM) guided by area under the concentration-time curve (an attempt to target an AUC > 400 µg•h/mL by Bayesian prediction: AUC400-guided TDM), the clinical efficacy of AUC400-guided TDM compared with trough concentration-guided TDM within 15-20 µg/mL (Trough15-20-guided TDM) has yet to be determined. We aimed to retrospectively evaluate the difference in the incidence rate of acute kidney injury (AKI), classified according to the Acute Kidney Injury Network, between these TDM groups. Individual AUC in the AUC400-guided TDM group was calculated by Bayesian prediction using trough and peak concentrations (within 3 h after the end of infusion). The AKI incidence in the Trough15-20-guided TDM group was 28.8% (15/52 patients) compared with an AKI incidence in the AUC400-guided TDM group of 9.1% (2/22 patients). Application of AUC400-guided TDM was identified as an independent factor for avoiding the incidence of AKI by Cox hazard regression analysis [hazard ratio = 0.168, 95% confidence interval (CI) 0.034-0.839] and logistic regression analysis (odds ratio = 0.037, 95% CI 0.003-0.285). As the estimated glomerular filtration rate (eGFR) improved, the surrogate target trough concentration for an AUC > 400 µg•h/mL was lowered (intercept 15.0074, slope -0.0598). In conclusion, AUC400-guided TDM may be superior to Trough15-20-guided TDM for the reduction of nephrotoxicity during vancomycin therapy.

Dalbavancin and telavancin in the treatment of infective endocarditis: a literature review.

Glycopeptides have an established role in the management of infective endocarditis, and feature in current treatment guidelines. Newer lipoglycopeptide agents (dalbavancin, telavancin and oritavancin), which are analogues of glycopeptides with structural modifications giving rise to added novel mechanisms of antimicrobial activity, are approved for the treatment of Gram-positive skin and skin structure infections, and also for nosocomial pneumonia (only telavancin has approval for the latter indication). Recent evidence has also emerged to support their use in the treatment of bone and joint infections. This article reviews the current literature on dalbavancin and telavancin in the treatment of infective endocarditis, a condition for which the role of these agents is yet to be established.

Microbiologic characteristics and antibiotic resistance rates of diabetic foot infections.

PURPOSE: the purpose of this research was to identify the sociodemographic and microbiological characteristics and antibiotic resistance rates of patients with diabetic foot infections, hospitalized in an emergency reference center. METHODS: it was an observational and transversal study. The sociodemographic data were collected by direct interview with the patients. During the surgical procedures, specimens of tissue of the infected foot lesions were biopsied to be cultured, and for bacterial resistance analysis. RESULTS: the sample consisted of 105 patients. The majority of patierns were men, over 50 years of age, married and with low educational level. There was bacterial growth in 95 of the 105 tissue cultures. In each positive culture only one germ was isolated. There was a high prevalence of germs of the Enterobacteriaceae family (51,5%). Gram-negative germs were isolated in 60% of cultures and the most individually isolated germs were the Gram-positive cocci, Staphylococcus aureus (20%) and Enterococcus faecalis (17,9%). Regarding antibiotic resistance rates, a high frequency of Staphylococcus aureus resistant to methicillin (63,0%) and to ciprofloxacin (55,5%) was found; additionally, 43,5% of the Gram-negative isolated germs were resistant to ciprofloxacin. CONCLUSIONS: the majority of patients were men, over 50 years of age, married and with low educational level. The most prevalent isolated germs from the infected foot lesions were Gram-negative bacteria, resistant to ciprofloxacin, and the individually most isolated germ was the methicillin resistant Staphylococcus aureus.

ACD: Antimicrobial chemotherapeutics database.

Antimicrobial resistance is becoming a growing health problem, which has become a challenge for the physicians to control infection and also an economic burden on the healthcare. This increase in resistance to the present antimicrobial agents led the researchers to find some alternative and more efficient drugs which can fight with the resistant microorganisms more effectively. Hence, in silico approach is used to design some novel drugs against various targets of microorganisms. For effective virtual screening of the drugs, there is a need to know about the chemical structure and properties of the antimicrobial agents. Therefore, we have prepared a comprehensive database as a platform for the researcher to search for possible lead molecules. Antimicrobial chemotherapeutics database (ACD) is comprised of ~4100 synthetic antimicrobial compounds as well as ~1030 active antimicrobial peptides. The Antimicrobial peptides are mainly from biological sources but some of them are synthetic in nature. Only those compounds, which are found to be active against either bacteria (both Gram-positive and negative) or fungus, are selected for this database.The ACD database is freely available at URL: http://amdr.amu.ac.in/acd, and it is compatible with desktops, smartphones, and tablets.