Liquid chromatography-tandem mass spectrometry methods for quantification of total and free antibiotic concentrations in serum and exudate from patients with post-sternotomy deep sternal wound infection receiving negative pressure wound therapy.

BACKGROUND: Systemically administered antibiotics are thought to penetrate the wounds more effectively during negative pressure wound therapy (NPWT).To test this hypothesis total and free antibiotic concentrations were quantified in serum and wound exudate. METHODS: UHPLC-MS/MS methods were developed and validated for the determination of ceftazidime, cefepime, cefotaxime, cefuroxime, cefazolin, meropenem, oxacillin, piperacillin with tazobactam, clindamycin, ciprofloxacin, sulfamethoxazole/trimethoprim (cotrimoxazole), gentamicin, vancomycin, and linezolid. The unbound antibiotic fraction was obtained by ultrafiltration using a Millipore Microcon-30kda Centrifugal Filter Unit. Analysis was performed on a 1.7-µm Acquity UPLC BEH C18 2.1 × 100-mm column with a gradient elution. RESULTS: The validation was performed for serum, exudates and free fractions. For all matrices, requirements were met regarding linearity, precision, accuracy, limit of quantitation, and matrix effect. The coefficient of variation was in the range of 1.2-13.6%.and the recovery 87.6-115.6%, respectively. Among the 29 applications of antibiotics thus far, including vancomycin, clindamycin, ciprofloxacin, oxacillin, cefepime, cefotaxime, cotrimoxazole, and gentamicin, total and free antibiotic concentrations in serum and exudate were correlated. CONCLUSION: This method can accurately quantify the total and free concentrations of 16 antibiotics. Comparison of concentration ratios between serum and exudates allows for monitoring individual antibiotics' penetration capacity in patients receiving NPWT.

Utilizing the photodynamic properties of curcumin to disrupt biofilms in Cutibacterium acnes: A promising approach for treating acne.

BACKGROUND: The treatment of acne vulgaris is often challenging due to the antibiotic resistance frequently observed in Cutibacterium acnes (C.acnes), a prevalent bacterium linked to this condition. OBJECTIVE: The objective of this research was to examine the impact of curcumin photodynamic therapy (PDT) on the survival of C.acnes and activity of biofilms produced by this microorganism. METHODS: Following the Clinical and Laboratory Standards Institute (CLSI) guidelines, we assessed the drug sensitivity of 25 clinical C.acnes strains to five antibiotics (erythromycin, clindamycin, tetracycline, doxycycline, minocycline) and curcumin by implementing the broth microdilution technique. In addition, we established C.acnes biofilms in a laboratory setting and subjected them to curcumin-PDT(curcumin combined with blue light of 180 J/cm2). Afterwards, we evaluated their viability using the XTT assay and observed them using confocal laser scanning microscopy. RESULTS: The result revealed varying resistance rates among the tested antibiotics and curcumin, with erythromycin, clindamycin, tetracycline, doxycycline, minocycline, and curcumin exhibiting resistance rates of 72 %, 44 %, 36 %, 28 %, 0 %, and 100 %, respectively. In the curcumin-PDT inhibition tests against four representative antibiotic-resistant strains, it was found that the survival rate of all strains of planktonic C. acnes was reduced, and the higher the concentration of curcumin, the lower the survival rate. Furthermore, in the biofilm inhibition tests, the vitality and three-dimensional structure of the biofilms were disrupted, and the inhibitory effect became more significant with higher concentrations of curcumin. CONCLUSION: The results emphasize the possibility of using curcumin PDT as an alternative approach for the treatment of C.acnes, especially in instances of antibiotic-resistant variations and infections related to biofilms.

[Systematic review and Meta-analysis of efficacy and safety of Kushen Gelatum combined with antibiotics in treatment of bacterial vaginosis].

This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P<0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P<0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P<0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P<0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P<0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.

Antibiotic Resistance among Fusobacterium, Capnocytophaga, and Leptotrichia Species of the Oral Cavity.

PURPOSE: Antibiotics play an important role in treating periodontal diseases. Due to the effectiveness of antibiotic therapies, their usage in dentistry has significantly increased. The aim of this study focused on the in-vitro susceptibility of different gram-negative oral bacteria species - which are associated with periodontal diseases (Fusobacterium spp., Capnocytophaga spp. and Leptotrichia buccalis) and have different geographical origins (Asia and Europe) - against antimicrobials that are clinically relevant in dental therapy. MATERIALS AND METHODS: A total of 45 strains were tested (29 Fusobacterium spp., 13 Capnocytophaga spp. and 3 L. buccalis) that were either isolated from Chinese patients or were obtained from different strain collections. Their antimicrobial susceptibility to the antimicrobial agents benzylpenicillin, amoxicillin, amoxicillin-clavulanic acid, ciprofloxacin, moxifloxacin, clindamycin, doxycycline, tetracycline and metronidazole was tested using the E-Test. Strains with particular resistance to penicillin, clindamycin and metronidazole were further analysed for resistance genes. RESULTS: All tested bacterial isolates were sensitive to amoxicillin, amoxicillin-clavulanic acid, doxycycline and tetracycline, but showed variable sensitivity towards other antibiotics such as benzylpenicillin, ciprofloxacin, moxifloxacin, clindamycin and metronidazole. CONCLUSION: The results of the present study suggest that certain periodontal disease-related bacterial strains can be resistant towards antimicrobial agents commonly used in adjuvant periodontal therapy.

Effects of mesotherapy introduction of compound glycyrrhizin injection on the treatment of moderate to severe acne.

BACKGROUND: Compound glycyrrhizin has achieved outstanding results in the treatment of various skin diseases. However, the use of mesotherapy to inject compound glycyrrhizin into the skin to treat acne is still understudied. AIMS: This paper aims to explore the effects of mesotherapy introduction of compound glycyrrhizin injection on the acne. MATERIALS & METHODS: A total of 108 patients were included in this study and divided into the control group (n = 54) and the observation group (n = 54). The control group was treated with topical clindamycin gel, while the study group was treated with topical clindamycin gel + mesotherapy and compound glycyrrhizin injection. Skin transepidermal water loss (TEWL), cuticle water content, acne severity, adverse reactions, and inflammatory reactions were documented before and after treatment in the two groups. RESULTS: The usage of mesotherapy to inject compound glycyrrhizin into the skin of acne patients more effectively treat acne than traditional clindamycin gel. The mesotherapy compound glycyrrhizin can more effectively protect the skin barrier of patients and reduce the loss of skin moisture. Compared with the traditional clindamycin gel, the combination of mesotherapy and compound glycyrrhizin more effectively inhibit the inflammatory reaction in acne patients and reduce skin damage in acne patients. DISCUSSION/CONCLUSION: Mesoderm introduction of compound glycyrrhizin injection has better effects on the treatment of moderate to severe acne than clindamycin gel.

Selective accumulation of pharmaceutical residues from 6 different soils by plants: a comparative study on onion, radish, and spinach.

The accumulation of six pharmaceuticals of different therapeutic uses has been thoroughly investigated and compared between onion, spinach, and radish plants grown in six soil types. While neutral molecules (e.g., carbamazepine (CAR) and some of its metabolites) were efficiently accumulated and easily translocated to the plant leaves (onion > radish > spinach), the same for ionic (both anionic and cationic) molecules seems to be minor to moderate. The maximum accumulation of CAR crosses 38,000 (onion), 42,000 (radish), and 7000 (spinach) ng g-1 (dry weight) respectively, in which the most majority of them happened within the plant leaves. Among the metabolites, the accumulation of carbamazepine 10,11-epoxide (EPC - a primary CAR metabolite) was approximately 19,000 (onion), 7000 (radish), and 6000 (spinach) ng g-1 (dry weight) respectively. This trend was considerably similar even when all these pharmaceuticals applied together. The accumulation of most other molecules (e.g., citalopram, clindamycin, clindamycin sulfoxide, fexofenadine, irbesartan, and sulfamethoxazole) was restricted to plant roots, except for certain cases (e.g., clindamycin and clindamycin sulfoxide in onion leaves). Our results clearly demonstrated the potential role of this accumulation process on the entrance of pharmaceuticals/metabolites into the food chain, which eventually becomes a threat to associated living biota.

Short term ciprofloxacin and clindamycin combination antibiotic therapy before and after transrectal ultrasound scan and prostate biopsy: Its impact on major components of gut microbiome.

The perturbation of gut microbiome is a risk factor for a number of adverse conditions. Among other factors antibiotic therapy is a common culprit. We characterized the short-term alteration of gut microbiome after antibiotic therapy. Nine patients (age (median [range]): 67 [57-75 years]) were subjected to prostate biopsy. Ciprofloxacin and clindamycin, 500 mg and 150 mg, respectively, were administered twice a day; this combination therapy was started the day before and continued until 5th and 8th day, respectively, following biopsy. 16s RNA sequencing data from fecal swabs taken before antibiotic therapy and 14 days after biopsy were analysed. At phylum level, the abundance of Actinobacteria and Firmicutes decreased, while that of Bacteroides and Proteobacteria increased after antibiotic therapy. The ratio of Firmicutes:Bacteroides inversed (from 2.81 to 0.74, p = 0.035). At order level, the abundance of Bacteroidales and Veillonellales increased, while that of Clostridiales and Coriobacteriales decreased. At genus level the abundance of Bacteroides increased, while those of Roseburia, Faecalibacterium and Collinsella decreased. These findings indicate that short-term antibiotic exposure skews gut microbiome composition. The current level of knowledge does not allow to decide whether this skewness is detrimental and has any long-term effect on disease including prostate pathology.

Short Communication: Enterotoxin Genes and Antibiotic Susceptibility of Bacillus cereus Isolated from Garlic Chives and Agricultural Environment.

This study aims to investigate the enterotoxin profiles and antibiotic susceptibility of Bacillus cereus isolated from garlic chives and environmental samples. A total of 103 B. cereus isolates were used to identify enterotoxin genes, including hblA, hblC, hblD, nheA, nheB, and nheC. The hemolysin BL enterotoxin complex (hblACD) was detected in 38 isolates (36.9%), and the non-hemolytic enterotoxin complex (nheABC) was detected in 8 (7.8%) isolates. Forty-five isolates (43.7%) had hblACD and nheABC genes. B. cereus was resistant to ß-lactam antibiotics and susceptible to non-ß-lactam antibiotics. However, some B. cereus strains showed intermediate resistance to ß-lactam and non-ß-lactam antibiotics. B. cereus isolated from garlic chives showed intermediate resistance to cefotaxime (7.7%), rifampin (15.4%), clindamycin (30.8%), erythromycin (7.7%), and tetracycline (7.7%). B. cereus isolates from the agricultural environment were moderately resistant to cefotaxime (18.9%), rifampin (15.6%), clindamycin (12.2%), erythromycin (4.4%), and tetracycline (5.6%). Moreover, B. cereus isolates from garlic chives and cultivation environments could change their antibiotic resistance profile from susceptible to intermediate-resistant to rifampin, clindamycin, erythromycin, and tetracycline and exhibit multidrug resistance. These results indicate that continuous monitoring of B. cereus contamination in the produce and agricultural environment might be needed to ensure the safety of consuming fresh vegetables.

Antimicrobial Resistance of Tannin Extract against E. coli Isolates from Sheep.

Plants have been long valuable sources of natural materials that have served to preserve human and animal health; as a result, pharmacological purposes have arisen from the use of plant compounds in most countries, according to a World Health Organization report. The present study aimed to assess the antimicrobial resistance of tannin extract against Escherichia coli (E. coli) isolates in sheep. A total of 100 samples from sheep were used to isolate E. coli and treated with tannin extract (90% purity) to investigate the in vitro effect, as compared to some antibiotics (Clindamycin, Cephalexin, Kanamycin, Tetracycline, and Vancomycin). The bacterial samples were cultured in a selective and differential medium, and Gram staining was used to examine them. The biochemical assays were performed to purify and expose these cultures; moreover, the API 20E system and RapidTM ONE kits were utilized to confirm the bacterial strain. Based on the findings, 50% of the samples showed a positive result for the presence of E. coli. The well diffusion technique was used to investigate the antibacterial activity to confirm the antibacterial action of tannin extract (from pomegranate peel) in different concentrations against E. coli. The highest zone of inhibition for the bacteria ranged from 12±0.5 to 30.3±0.2 at 50% concentrations, proving that tannins extract was significantly effective against E. coli. The presence of E. coli was detected in 50 % of the samples. The well-diffusion technique was used to evaluate the antimicrobial property of tannin extract through various concentrations with the highest zone of inhibition for the bacteria ranging from 12.5 to 30.30.2 at 50%, demonstrating that tannin extract was significantly effective on E. coli.

Increased Prevalence of Minocycline-Resistant Staphylococcus epidermidis with tet(M) by Tetracycline Use for Acne Treatment.

Staphylococcus epidermidis, a major skin bacterium, can cause opportunistic infections. Use of antimicrobial agents against Cutibacterium acnes for acne treatment becomes a risk factor for emergence of antimicrobial-resistant skin bacteria. In this study, the impact of antimicrobial treatment of acne vulgaris on S. epidermidis antimicrobial resistance was assessed. A total of 344 S. epidermidis strains isolated from patients with acne vulgaris who visited hospital (165 strains) and dermatological clinics (179 strains), respectively, were analyzed. Except for doxycycline, the resistance rates were higher in strains isolated from patients who had used antimicrobials for acne treatment than in those isolated from patients who had not used antimicrobials. The prevalence rates of strains with erm(C) from patients who used macrolides and clindamycin (hospital, 78.0%; clinics, 61.3%) and those of strains with tet(M) from patients who used tetracyclines (hospital, 27.5%; clinics, 42.4%) were significantly higher than those of strains from patients who did not use antimicrobials (p < 0.05). All strains with erm(A) (8/8) and 91.7% strains with erm(C) (156/170) showed high-level resistance to macrolides and clindamycin (MIC ≥256 µg/mL). Furthermore, almost all strains with tet(M) showed resistance to minocycline. Our results showed that the use of antimicrobials for acne treatment may lead to an increased prevalence of antimicrobial-resistant S. epidermidis. In particular, the emergence of minocycline-resistant strains with tet(M) owing to the use of tetracyclines (doxycycline and minocycline) is a critical issue. Appropriate antimicrobial use for acne treatment may be an important strategy to prevent the emergence of antimicrobial-resistant skin bacteria.

Accurate 16S Absolute Quantification Sequencing Revealed Vaginal Microecological Composition and Dynamics During Mixed Vaginitis Treatment With Fufang FuRong Effervescent Suppository.

Background: The diagnosis and treatment of mixed vaginitis are more complicated than single pathogenic infections, and there may be adverse reactions and several contraindications to conventional antibiotic therapy. Therefore, this study aimed to evaluate the preliminary effects of Fufang Furong Effervescent Suppository for the management of aerobic vaginitis (AV) mixed with bacterial vaginosis (BV) using Accurate 16S absolute quantification sequencing (Accu16S). Methods: In the present randomized, blind, multi-center clinical trial, women (20 to 55 years) who had received a diagnosis of AV+BV were randomly assigned into clindamycin positive control (n = 41) and Fufang Furong Effervescent Suppository (n = 39) groups. The follow-up occurred in three time periods (V1: -2~0 days; V2: 15-17 days; V3: 40 ± 3 days). At each visit, two vaginal swabs, one for clinical evaluation and one for laboratory examination, were taken from each patient. The Nugent score, Donders' score, drug-related complications, recurrence rates, and microecological changes of vaginal swabs were assessed in the time three periods. Results: At baseline, the two groups were similar in frequency of presentation with vaginal burning, odor, abnormal discharge, and itching. No meaningful differences in Nugent and Donders' scores were detected between the two groups at stage V2 (Nugent: p = 0.67; Donders': p = 0.85) and V3 (Nugent: p = 0.97; Donders: p = 0.55). The Furong group presented fewer complications compared to the Clindamycin group. However, this difference was not statistically significant (p = 0.15). Additionally, Accu16S indicated that the total abundance of bacteria in both groups sharply decreased in stage V2, but slightly increased in V3. In stage V3, the absolute abundance of Lactobacillus in the Furong group was considerably higher compared to untreated samples (p < 0.05). On the other hand, no momentous increase was detected in the Clindamycin group (p > 0.05). Conclusion: Fufang Furong Effervescent Suppository can be as effective as clindamycin cream in the management of AV+BV while may restore the vagina microecosystem better.

Is clindamycin a potential treatment for prostatitis?

Cutibacterium acnes has been associated with chronic prostatitis, which can potentially favor the appearance of tumors in the prostate. Prostatitis is difficult to treat, and the drug needs to be able to penetrate the prostate. The aim was to investigate the pharmacokinetics of clindamycin in the interstitial fluid of rat prostate using microdialysis. Microdialysis probes were recovered in vitro and in vivo. Clindamycin was administered at 80 mg/kg iv bolus for plasma and tissue pharmacokinetic experiments. A microdialysis probe was implanted in the prostate gland for collections over an 8-hour period. The pharmacokinetic parameters were determined by both compartmental and non-compartmental approaches. Penetration was determined as the ratio between the area under the curve and the time of the clindamycin measurement in the prostate. The recovery of the in vivo probes was 38.11 ± 1.14%. The plasma profile was modeled by a two-compartment pharmacokinetic model. Clindamycin presented a prostate/plasma ratio of 1.02, with free concentrations above the minimum inhibitory concentration for Cutibacterium acnes isolates. This was the first study that determined clindamycin free concentrations in the prostatic fluid of rats. These findings suggest that clindamycin may be an effective alternative for the treatment of prostatitis caused by Cutibacterium acnes.

The Bacteriology of Skin Lesions in Patients with Hidradenitis Suppurativa Is Associated with Previous Antibiotic Treatment in the Community Setting: A Referral Center Experience.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic skin disease characterized by inflammatory nodules and abscesses. The pathogenic role of bacteria is not fully understood. As the diagnosis is usually delayed, patients are often treated with several lines of antibiotics in a nonstandardized fashion. The aim of the study was to investigate and compare the bacteriology of active HS lesions in patients treated or not treated with antibiotics in the community setting before referral to a dedicated HS clinic. METHODS: Purulent skin lesions of patients with HS referred to the HS Clinic of Rabin Medical Center in 2009-2020 were cultured. Data were collected from the patients' medical files and microbiology reports. The correlation between the location of the skin lesion and the bacteriologic profile was analyzed, and the effects of previous antibiotic treatment on the bacteriologic profile of the lesions and susceptibility patterns of the cultured bacteria were evaluated. RESULTS: Pus (or tissue) from inflammatory lesions of 97 patients with HS was cultured. Mean (SD) patient age was 39.5 (13.0) years, and mean delay in diagnosis was 7.3 (8.3) years. Most patients (57.7%) had dominant involvement of one location, with the most active lesions concentrated in the genitalia, gluteal/perineal area, and axilla. Enterobacterales species were the most frequent isolates detected in all locations except the face and scalp. Seventy-eight patients (80.4%) had been treated in the community setting prior to referral with a median (range) of 2 (1-8) lines of antibiotics. The most commonly prescribed antibiotics were amoxicillin/clavulanate (22.0%), doxycycline/minocycline (16.8%), clindamycin (16.2%; monotherapy 8.1%, clindamycin with rifampicin 8.1%), and cephalexin (13.9%). Compared to the previously untreated patients, cultures of lesions from the previously treated patients yielded a higher percentage of gram-negative Enterobacterales (the most common isolates in this group) (31.3% vs. 10.3%) and a significantly higher median number of isolates per culture (2 vs. 1, p < 0.0001). Gram-positive bacteria, usually considered contaminants (mainly coagulase-negative staphylococci) accounted for 31.0% of the isolates in the previously treated group. Susceptibility testing for the entire cohort revealed 100% bacterial sensitivity to ciprofloxacin. Staphylococcus spp. were 100% sensitive to rifampicin. Both gram-positive and gram-negative bacteria had high sensitivity to trimethoprim and sulfamethoxazole. CONCLUSION: Nonstandardized antibiotic treatment of HS in the community setting can skew the microbiology of skin lesions toward gram-negative bacteria. Therefore, treatment with trimethoprim and sulfamethoxazole or ciprofloxacin, either alone or combined with rifampicin, may be considered.

Epidemiological Characterization of Group B Streptococcus Infections in Alberta, Canada: An Update from 2014 to 2020.

Group B Streptococcus (GBS) is a leading cause of invasive neonatal disease. Epidemiological surveillance of GBS is important to determine cumulative incidence, antimicrobial resistance rates, and maternal and neonatal disease prevention. In this study, we present an update on GBS epidemiology in Alberta, Canada, from 2014 to 2020. Over the 7-year period, 1,556 GBS isolates were submitted to the Alberta Public Health Laboratory for capsular polysaccharide (CPS) typing and antimicrobial susceptibility testing. We analyzed the distribution of CPS types in Alberta and found CPS types III (23.6%), Ia (16.0%), Ib (14.8%), II (13.3%), V (12.7%), IV (12.5%), and VI (2.38%) to be the most prevalent. Less than 1% each of CPS types VII, VIII, and IX were identified. In agreement with historical data, the presence of CPS type IV continued to rise across Alberta, particularly in cases of adult infection, where a 2-fold increase was observed. Cumulative incidences of GBS cases per 100,000 population and late-onset disease per 1,000 live births increased from 4.43 to 5.36 and 0.38 to 0.41, respectively, from 2014 to 2020. However, the incidence of early-onset disease decreased during the 7-year period from 0.2 to 0.07, suggestive of successful intrapartum chemoprophylaxis treatment programs. All GBS isolates were susceptible to penicillin and vancomycin. However, nonsusceptibility to erythromycin increased significantly, from 36.85% to 50.8%, from 2014 to 2020. Similarly, nonsusceptibility to clindamycin also increased significantly, from 21.0% to 45.8%. In comparison to historical data, the overall rates of GBS infection and antimicrobial resistance have increased and the predominant CPS types have changed. IMPORTANCE This work describes the epidemiology of invasive infections caused by the bacterium group B Streptococcus (GBS) in Alberta, Canada. We show that rates of invasive GBS disease have increased from 2014 to 2020 for both adult disease and late-onset disease in neonates, whereas the rate of early onset disease in neonates has decreased. We also show that the rate of resistance to erythromycin (an antibiotic used to treat GBS) has also increased in this time.

Labdane Diterpenoids from Salvia tingitana Etl. Synergize with Clindamycin against Methicillin-Resistant Staphylococcus aureus.

Quorum-sensing (QS) is a regulatory mechanism in bacterial communication, important for pathogenesis control. The search for small molecules active as quorum-sensing inhibitors (QSI) that can synergize with antibiotics is considered a good strategy to counteract the problem of antibiotic resistance. Here the antimicrobial labdane diterpenoids sclareol (1) and manool (2) extracted from Salvia tingitana were considered as potential QSI against methicillin-resistant Staphylococcus aureus. Only sclareol showed synergistic activity with clindamycin. The quantification of these compounds by LC-MS analysis in the organs and in the calli of S. tingitana showed that sclareol is most abundant in the flower spikes and is produced by calli, while manool is the major labdane of the roots, and is abundant also in the leaves. Other metabolites of the roots were abietane diterpenoids, common in Salvia species, and pentacyclic triterpenoids, bearing a γ-lactone moiety, previously undescribed in Salvia. Docking simulations suggested that 1 and 2 bind to key residues, involved in direct interactions with DNA. They may prevent accessory gene regulator A (AgrA) binding to DNA or AgrA activation upon phosphorylation, to suppress virulence factor expression. The antimicrobial activity of these two compounds probably achieves preventing upregulation of the accessory gene regulator (agr)-regulated genes.

Evaluation of the synergistic antimicrobial effect of folk medicinal plants with clindamycin against methicillin-resistant Staphylococcus aureus strains.

Antibiotic resistance has become a major worldwide priority, and identifying natural antimicrobial compounds may help overcome this problem. In this study, ethanolic extracts of 12 plants commonly used in traditional medicine were tested against two strains of methicillin-resistant Staphylococcus aureus (ATCC 33591 and ATCC 43300) in terms of minimum inhibitory concentrations (MICs). Furthermore, the effect of combining plant extracts with clindamycin antibiotic was also investigated using the checkerboard method. Among the tested plants, Camellia sinensis, Thymus vulgaris, Rosmarinus officinalis and Salvia officinalis exhibited potent inhibitory activity against both strains with MICs ranges (125-500 µg ml-1 ). Synergistic activity was confirmed for the four plants combined with clindamycin with fractional inhibitory concentration index <0·5. However, no antagonistic activity was found for these combinations. Our findings suggest that using an antibiotics-plants combination might be a successful technique to reduce antibiotic consumption, which would overcome the antibiotics resistance or delay its onset.

Hybrid donor-acceptor polymer nanoparticles and combination antibiotic for mitigation of pathogenic bacteria and biofilms.

Biofilms pose a significant clinical problem in skin and soft tissue infections. Their resistance to antibiotics has spurred investigations into alternative treatments, such as nanoparticle-mediated photothermal ablation. Non-toxic Hybrid Donor- Acceptor (DA) Polymer nanoParticles (H-DAPPs) were developed for fluorescence imaging (using poly(3-hexylthiophene-2,5 diyl) (P3HT)) and rapid, near-infrared photothermal ablation (NIR- PTA) (using poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b']dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe)). H-DAPPs were evaluated alone, and in combination with antibiotics, against planktonic S. aureus and S. pyogenes, and S. aureus biofilms. H-DAPPs NIR-PTA (15-700 µg/ mL) can generate rapid temperature changes of 27.6-73.1 °C, which can eradicate planktonic bacterial populations and reduce biofilm bacterial viability by more than 4- log (> 99.99%) with exposure to 60 s of 800 nm light. Reductions were confirmed via confocal analysis, which suggested that H-DAPPs PTA caused bacterial inactivation within the biofilms, but did not significantly reduce biofilm polysaccharides. SEM imaging revealed structural changes in biofilms after H-DAPPs PTA. S. aureus biofilms challenged with 100 µg/mL of H-DAPPs (H-DAPPs-100) to induce an average temperature of 55.1 °C, and the minimum biofilm eradication concentration (MBEC) of clindamycin, resulted in up to ~3- log decrease in bacterial viability compared to untreated biofilms and those administered H-DAPPs-100 PTA only, and up to ~2- log compared to biofilms administered only clindamycin. This study demonstrates that polymer nanoparticle PTA can mitigate biofilm infection and may improve antimicrobial efficacy.

Evodiamine Enhanced the Anti-Inflammation Effect of Clindamycin in the BEAS-2B Cells Infected with H5N1 and Pneumoniae D39 Through CREB-C/EBPß Signaling Pathway.

Pneumonia is a pulmonary disease among children. Evodiamine, a traditional Chinese medicine, is known for anti-inflammatory effect. This study aimed to investigate the impact of evodiamine on severe pneumonia-like cells and the underlying mechanism involved. H5N1 and pneumoniae D39 was used to induce severe pneumonia-like conditions in BEAS-2B cells. The cell viability in BEAS-2B cells after treatments with 0, 20, 40, 60, 80, and 100 µM evodiamine was examined using MTT assays. The protein concentrations of inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß, and Toll-like receptors (TLRs) were measured by enzyme-linked immunosorbent assay methods and the protein and mRNA changes in C/EBPß/CREB were measured using Real Time-quantitative polymerase chain reaction and Western blot methods. Our results revealed that Evodiamine significantly decreased TNF-α, IL-6, and IL-1ß in BEAS-2B cells. Moreover, evodiamine markedly reduced TLR2,3,4 protein expression and the phosphorylated protein of C/EBPß and CREB. Besides, evodiamine combined with clindamycin exerted more significant effects than clindamycin alone. Taken together, our results demonstrated that evodiamine enhanced the anti-inflammation effect of clindamycin in the BEAS-2B cells infected with H5N1 and pneumoniae D39 through CREB-C/EBPß signaling pathway.