Evaluation of a New 'Mix-In' Style Glycomacropeptide-Based Protein Substitute for Food and Drinks in Patients with Phenylketonuria and Tyrosinemia.

(1) Background: Poor palatability, large volume, and lack of variety of some liquid and powdered protein substitutes (PSs) for patients with phenylketonuria (PKU) and tyrosinemia (TYR) can result in poor adherence. This study aimed to evaluate a new unflavoured, powdered GMP-based PS designed to be mixed into drinks, foods, or with other PSs, in patients with PKU and TYR. (2) Methods: Paediatric and adult community-based patients were recruited from eight metabolic centres and prescribed ≥1 sachet/day (10 g protein equivalent (PE)) of the Mix-In-style PS over 28 days. Adherence, palatability, GI tolerance, and metabolic control were recorded at baseline and follow-up. Patients who completed at least 7 days of intervention were included in the final analysis. (3) Results: Eighteen patients (3-45 years, nine males) with PKU (n = 12) and TYR (n = 6) used the Mix-In-style PS for ≥7 days (mean 26.4 days (SD 4.6), range 11-28 days) alongside their previous PS, with a mean intake of 16.7 g (SD 7.7) PE/day. Adherence was 86% (SD 25), and GI tolerance was stable, with n = 14 experiencing no/no new symptoms and n = 3 showing improved symptoms compared to baseline. Overall palatability was rated satisfactory by 78% of patients, who successfully used the Mix-In-style PS in various foods and drinks, including smoothies, squash, and milk alternatives, as a top-up to meet their protein needs. There was no concern regarding safety/metabolic control during the intervention. (4) Conclusions: The 'Mix-In'-style PS was well adhered to, accepted, and tolerated. Collectively, these data show that providing a flexible, convenient, and novel format of PS can help with adherence and meet patients' protein needs.

The Potential Utility of Single-Dose Long-Acting Intravenous Antibiotics for Acute Bacterial Skin and Skin-Structure Infections in the Emergency Department.

Acute bacterial skin and skin-structure infections (ABSSSIs) are frequent clinical presentations to emergency departments (EDs) across the nation that can require substantial resources to treat due to several factors. These include an increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) as the causative organism, limited availability of oral antibiotics that treat ABSSSIs secondary to MRSA, absorption and pharmacodynamic concerns with oral therapy, and regimen adherence. In patients who are unable to tolerate oral therapy, or are unable to adhere to prescribed antibiotics, inpatient admission for intravenous (IV) antibiotics may be necessary. Although inpatient IV antibiotics used to treat MRSA, such as vancomycin, are relatively inexpensive, hospital admission itself incurs significant associated costs. The introduction of the long-acting lipoglycopeptides, dalbavancin and oritavancin, has many potential advantages for the treatment of ABSSSIs including one- or two-dose regimens, allowing patients to receive their dose in the ED or infusion center and avoid inpatient admission altogether. Existing data have borne out these results, demonstrating that these agents can significantly reduce the length of hospital stay and the overall treatment cost of ABSSSIs. However, as these agents have nontraditional therapeutic regimens compared with alternative IV and oral agents that require consistent dosing, it is imperative to have decision support tools in place to ensure that this therapy is utilized in appropriate patients with ABSSSIs and that its true benefits can be realized for both the patient and the health care system.

Synthetic Biology Facilitates Semisynthetic Development of Type V Glycopeptide Antibiotics Targeting Vancomycin-Resistant Enterococcus.

The continued efficacy of glycopeptide antibiotics (GPAs) against Gram-positive bacteria is challenged by the emergence and spread of GPA-resistant pathogens, particularly vancomycin-resistant enterococci (VRE). The growing frequency of GPA resistance propels the need for innovative development of more effective antibiotics. Unlike canonical GPAs like vancomycin, Type V GPAs adopt a distinct mode of action by binding peptidoglycan and blocking the activity of autolysins essential for cell division, rendering them a promising class of antibiotics for further development. In this study, the Type V GPA, rimomycin A, was modified to generate 32 new analogues. Compound 17, derived from rimomycin A through N-terminal acylation and C-terminal amidation, exhibited improved anti-VRE activity and solubility. In a VRE-A neutropenic thigh infection mouse model, compound 17 significantly lowered the bacterial load by 3-4 orders of magnitude. This study sets the stage to develop next-generation GPAs in response to growing VRE infections.

The Role of Arginine-Vasopressin in Stroke and the Potential Use of Arginine-Vasopressin Type 1 Receptor Antagonists in Stroke Therapy: A Narrative Review.

Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences.

Relapsing and refractory peritoneal dialysis peritonitis caused by Corynebacterium amycolatum.

BACKGROUND: Peritonitis is an important complication and cause of morbidity in patients undergoing peritoneal dialysis (PD). Corynebacterium species, often considered skin and mucosal contaminants, are a rare cause of PD-associated peritonitis and have been acknowledged in published guidelines for the diagnosis and treatment of PD peritonitis only over the last decade. CASE-DIAGNOSIS/TREATMENT: We present two children with difficult-to-treat episodes of PD peritonitis due to Corynebacterium amycolatum. Episodes were associated with fever, abdominal pain and cloudy dialysate, high dialysate polymorphonuclear leukocyte counts, and elevated serum C-reactive protein and procalcitonin concentrations. Symptoms persisted beyond 5 days in 4 of 5 peritonitis episodes, and peritonitis relapsed despite in vitro sensitivity of the bacterial isolates to guideline-recommended antibiotics. C. amycolatum was cultured from the PD catheter tip despite 4 weeks of intraperitoneal glycopeptide therapy and clinical peritonitis resolution suggestive of efficient biofilm formation. Our systematic literature search identified three previous (adult) case descriptions of C. amycolatum peritonitis, all with repeat episodes by the same organism. The incidence of C. amycolatum as a cause of PD peritonitis has not yet been established but is likely underreported due to challenges in species differentiation. CONCLUSIONS: C. amycolatum is a rarely identified cause of refractory and/or relapsing PD peritonitis. Species differentiation of non-diphtheriae Corynebacterium isolates is critical, and prolonged antibiotic treatment, preferably with a glycopeptide antibiotic, is recommended, with a low threshold for PD catheter change or removal in case of repeat peritonitis.

Xenopus GLP-1-based glycopeptides as dual glucagon-like peptide 1 receptor/glucagon receptor agonists with improved in vivo stability for treating diabetes and obesity.

Peptide dual agonists toward both glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) are emerging as novel therapeutics for the treatment of type 2 diabetes mellitus (T2DM) patients with obesity. Our previous work identified a Xenopus GLP-1-based dual GLP-1R/GCGR agonist termed xGLP/GCG-13, which showed decent hypoglycemic and body weight lowering activity. However, the clinical utility of xGLP/GCG-13 is limited due to its short in vivo half-life. Inspired by the fact that O-GlcNAcylation of intracellular proteins leads to increased stability of secreted proteins, we rationally designed a panel of O-GlcNAcylated xGLP/GCG-13 analogs as potential long-acting GLP-1R/ GCGR dual agonists. One of the synthesized glycopeptides 1f was found to be equipotent to xGLP/GCG-13 in cell-based receptor activation assays. As expected, O-GlcNAcylation effectively improved the stability of xGLP/GCG-13 in vivo. Importantly, chronic administration of 1f potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, and normalized lipid metabolism and adiposity in both db/db and diet induced obesity (DIO) mice models. These results supported the hypothesis that glycosylation is a useful strategy for improving the in vivo stability of GLP-1-based peptides and promoted the development of dual GLP-1R/GCGR agonists as antidiabetic/antiobesity drugs.

Postexposure Prophylaxis and Treatment of Bacillus anthracis Infections: A Systematic Review and Meta-analyses of Animal Models, 1947-2019.

BACKGROUND: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. METHODS: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. RESULTS: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, ß-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. CONCLUSIONS: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.

A lipoglycopeptide antibiotic for Gram-positive biofilm-related infections.

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria (Staphylococcus aureus and Streptococcus pneumoniae) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally. We have developed a preclinical glycopeptide antibiotic, MCC5145, that has excellent potency (MIC90 ≤ 0.06 µg/ml) against hundreds of isolates of methicillin-resistant S. aureus (MRSA) and other Gram-positive bacteria, with a greater than 1000-fold margin over mammalian cell cytotoxicity values. The antibiotic has therapeutic in vivo efficacy when dosed subcutaneously in multiple murine models of established bacterial infections, including thigh infection with MRSA and blood septicemia with S. pneumoniae, as well as when dosed orally in an antibiotic-induced Clostridioides difficile infection model. MCC5145 exhibited reduced nephrotoxicity at microbiologically active doses in mice compared to vancomycin. MCC5145 also showed improved activity against biofilms compared to vancomycin, both in vitro and in vivo, and a low propensity to select for drug resistance. Characterization of drug action using a transposon library bioinformatic platform showed a mechanistic distinction from other glycopeptide antibiotics.

Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections.

PURPOSE: This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI). MATERIALS AND METHODS: We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis. RESULTS: A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71-6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis. CONCLUSION: Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.

New Perspectives on Antimicrobial Agents: Long-Acting Lipoglycopeptides.

The long-acting lipoglycopeptides (LGPs) dalbavancin and oritavancin are semisynthetic antimicrobials with broad and potent activity against Gram-positive bacterial pathogens. While they are approved by the Food and Drug Administration for acute bacterial skin and soft tissue infections, their pharmacological properties suggest a potential role of these agents for the treatment of deep-seated and severe infections, such as bloodstream and bone and joint infections. The use of these antimicrobials is particularly appealing when prolonged therapy, early discharge, and avoidance of long-term intravascular catheter access are desirable or when multidrug-resistant bacteria are suspected. This review describes the current evidence for the use of oritavancin and dalbavancin in the treatment of invasive infections, as well as the hurdles that are preventing their optimal use. Moreover, this review discusses the current knowledge gaps that need to be filled to understand the potential role of LGPs in highly needed clinical scenarios and the ongoing clinical studies that aim to address these voids in the upcoming years.

Cost-minimisation analysis of oritavancin for the treatment of acute bacterial skin and skin structure infections from a United Kingdom perspective.

BACKGROUND: Early discharge (ED) from hospital and outpatient parenteral antibiotic therapy (OPAT) are effective approaches for the management of a range of infections, including acute bacterial skin and skin structure infections (ABSSSI). Strategies that facilitate ED, thereby reducing complications such as healthcare-acquired infection whilst enhancing patient quality of life, are being increasingly adopted in line with good antimicrobial stewardship practice. This study presents a cost-minimisation analysis for the use of oritavancin at ED versus relevant comparators from a National Health Service (NHS) and personal and social services United Kingdom perspective. METHODS: A cost-minimisation model considering adult patients with ABSSSI with suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) infection, was developed based on publicly available NHS costs, practice guidelines for ABSSSI and clinical expert's opinion. Cost of treatment and treatment days were compared for oritavancin at ED to dalbavancin, teicoplanin, daptomycin and linezolid. RESULTS: Following the empiric use of either flucloxacillin or vancomycin in the inpatient setting, oritavancin was compared to OPAT with dalbavancin, teicoplanin and daptomycin, and oral linezolid from day 4 of treatment. Oritavancin at ED reduced treatment duration by 0.8 days and led to cost savings of £281 in comparison to dalbavancin. In comparison to teicoplanin, daptomycin and linezolid, oritavancin reduced treatment duration by 5 days, with marginally higher costs (£446, £137, and £1,434, respectively). CONCLUSION: Oritavancin, used to support ED, is associated with lower costs compared with dalbavancin and reduced treatment duration relative to all comparators. Its use would support an ED approach in MRSA ABSSSI management.

Efficacy and safety of novel glycopeptides versus vancomycin for the treatment of gram-positive bacterial infections including methicillin resistant Staphylococcus aureus: A systematic review and meta-analysis.

OBJECTIVE: To compare between current evidence of novel glycopeptides against vancomycin for the treatment of gram-positive bacterial infections. METHODOLOGY: A systematic review and meta-analysis was done. Major databases were searched for eligible randomized control trials that assessed clinical success, microbiological success and safety profile of novel glycopeptides versus vancomycin for infections caused by gram-positive bacteria. RESULTS: This meta-analysis included eleven trials (7289 participants) comparing telavancin, dalbavancin and oritavancin with vancomycin. No differences were detected between novel glycopeptides and vancomycin for the treatment of skin and soft tissue infections (SSTIs) among modified intent-to-treat patients (OR: 1.04, CI: 0.92-1.17) as well as within the clinically evaluable patients (OR: 1.09, CI: 0.91-1.30). Data analysed from SSTIs, HAP and bacteremia studies on telavancin showed insignificant high clinical response in microbiologically evaluable patients infected with methicillin resistant Staphylococcus aureus (MRSA) (OR: 1.57, CI: 0.94-2.62, p: 0.08) and in the eradication of MRSA (OR: 1.39, CI: 0.99-1.96, P:0.06). Dalbavancin was non-inferior to vancomycin for the treatment of osteomyelitis in a phase II trial, while it was superior to vancomycin for the treatment of bacteremia in a phase II trial. Data analysed from all trials showed similar rates of all-cause mortality between compared antibiotics groups (OR: 0.67, CI: 0.11-4.03). Telavancin was significantly related with higher adverse events (OR: 1.24, CI: 1.07-1.44, P: <0.01) while dalbavancin and oritavancin were associated with significant fewer adverse events (OR: 0.73, CI: 0.57-0.94, p: 0.01; OR: 0.72, CI: 0.59-0.89, p: <0.01 respectively). CONCLUSION: Efficacy and safety profiles of both dalbavancin and oritavancin were the same as vancomycin in the treatment of gram-positive bacterial infections in different clinical settings, while telavancin might be an effective alternative to vancomycin in MRSA infections, but caution is required during its clinical use due to the high risk of adverse events, especially nephrotoxicity.

Antimicrobial Susceptibility Trends and Risk Factors for Antimicrobial Resistance in Pseudomonas aeruginosa Bacteremia: 12-Year Experience in a Tertiary Hospital in Korea.

BACKGROUND: Infections caused by multidrug-resistant Pseudomonas aeruginosa (MDRPA) have been on the rise worldwide, and delayed active antimicrobial therapy is associated with high mortality. However, few studies have evaluated increases in P. aeruginosa infections with antimicrobial resistance and risk factors for such antimicrobial resistance in Korea. Here, we analyzed changes in antimicrobial susceptibility associated with P. aeruginosa bacteremia and identified risk factors of antimicrobial resistance. METHODS: The medical records of patients with P. aeruginosa bacteremia who were admitted to a tertiary hospital between January 2009 and October 2020 were retrospectively reviewed. Antibiotic resistance rates were compared among the time periods of 2009-2012, 2013-2016, and 2017-2020 and between the intensive care unit (ICU) and non-ICU setting. Empirical antimicrobial therapy was considered concordant, if the organism was susceptible to antibiotics in vitro, and discordant, if resistant. RESULTS: During the study period, 295 patients with P. aeruginosa bacteremia were identified. The hepatobiliary tract (26.8%) was the most common primary site of infection. The rates of carbapenem-resistant P. aeruginosa (CRPA), MDRPA, and extensively drug-resistant P. aeruginosa (XDRPA) were 24.7%, 35.9%, and 15.9%, respectively. XDRPA showed an increasing trend, and CRPA, MDRPA, and XDRPA were also gradually increasing in non-ICU setting. Previous exposure to fluoroquinolones and glycopeptides and urinary tract infection were independent risk factors associated with CRPA, MDRPA, and XDRPA. Previous exposure to carbapenems was an independent risk factor of CRPA. CRPA, MDRPA, and XDRPA were associated with discordant empirical antimicrobial therapy. CONCLUSION: The identification of risk factors for antimicrobial resistance and analysis of antimicrobial susceptibility might be important for concordant empirical antimicrobial therapy in patients with P. aeruginosa bacteremia.

The Distribution of Multidrug-resistant Microorganisms and Treatment Status of Hospital-acquired Pneumonia/Ventilator-associated Pneumonia in Adult Intensive Care Units: a Prospective Cohort Observational Study.

BACKGROUND: It is essential to determine the distribution of the causative microorganisms in the region and the status of local antibiotic resistance for the proper treatment of hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP). This study aimed to investigate the occurrence and causative strains of HAP/VAP, distribution of resistant bacteria, use of antibiotics, and the ensuing outcomes of patients in Korea. METHODS: A multicenter prospective observational cohort study was conducted among patients with HAP/VAP admitted to the medical intensive care unit of 5 tertiary referral centers between August 2012 and June 2015. Patients' demographic and clinical data were collected. RESULTS: A total of 381 patients were diagnosed with HAP/VAP. Their median age was 69 (59-76) years and 71% were males. A majority of the patients (88%) had late-onset (> 5 days) HAP/VAP. One-quarter of the patients (n = 99) had at least one risk factor for multidrug-resistant (MDR) pathogens, such as prior intravenous antibiotic use within the last 90 days. Microbiological specimens were mostly obtained noninvasively (87%) using sputum or endotracheal aspirates. Pathogens were identified in 235 (62%) of the 381 patients. The most common bacterial pathogen was Acinetobacter baumannii (n = 89), followed by Staphylococcus aureus (n = 52), Klebsiella pneumoniae (n = 25) and Pseudomonas aeruginosa (n = 22). Most of isolated A. baumannii (97%) and S. aureus (88%) were multidrug resistant. The most commonly used empirical antibiotic regimens were carbapenem-based antibiotics (38%), followed by extended-spectrum penicillin/ß-lactamase inhibitor (34%). Glycopeptide or linezolid were also used in combination in 54% of patients. The 28-day mortality rate of the patients with HAP/VAP was 30% and the 60-day mortality was 46%. Patients who used empirical antibiotics appropriately had significantly lower mortality rates than those who did not (28-day mortality: 25% vs. 40%, P = 0.032; 60-day mortality: 41% vs. 55%, P = 0.032, respectively). Administration of appropriate empirical antibiotics (odds ratio [OR], 0.282; confidence interval [CI], 0.092-0.859; P = 0.026), Day 7 treatment failure (OR, 4.515; CI, 1.545-13.192; P = 0.006), and APACHE II score on day 1 (OR, 1.326; CI, 0.988-1.779; P = 0.012) were the factors that determined the 28-day mortality in patients with HAP who had identified bacteria as pathogens. CONCLUSION: In HAP/VAP patients, there was a large burden of MDR pathogens, and their associated mortality rate was high. Proper selection of empirical antibiotics was significantly associated with the patient's prognosis; however, there was a discrepancy between major pathogens and empirical antibiotic therapy.

Repurposing of antibiotics for clinical management of COVID-19: a narrative review.

BACKGROUND: Drug repurposing otherwise known as drug repositioning or drug re-profiling is a time-tested approach in drug discovery through which new medical uses are being established for already known drugs. Antibiotics are among the pharmacological agents being investigated for potential anti-SARS-COV-2 activities. The antibiotics are used either to resolve bacterial infections co-existing with COVID-19 infections or exploitation of their potential antiviral activities. Herein, we aimed to review the various antibiotics that have been repositioned for the management of COVID-19. METHODS: This literature review was conducted from a methodical search on PubMed and Web of Science regarding antibiotics used in patients with COVID-19 up to July 5, 2020. RESULTS: Macrolide and specifically azithromycin is the most common antibiotic used in the clinical management of COVID-19. The other antibiotics used in COVID-19 includes teicoplanin, clarithromycin, doxycycline, tetracyclines, levofloxacin, moxifloxacin, ciprofloxacin, and cefuroxime. In patients with COVID-19, antibiotics are used for their immune-modulating, anti-inflammatory, and antiviral properties. The precise antiviral mechanism of most of these antibiotics has not been determined. Moreover, the use of some of these antibiotics against SARS-CoV-2 infection remains highly controversial and not widely accepted. CONCLUSION: The heavy use of antibiotics during the COVID-19 pandemic would likely worsen antibiotic resistance crisis. Consequently, antibiotic stewardship should be strengthened in order to prevent the impacts of COVID-19 on the antibiotic resistance crisis.

Daptomycin versus teicoplanin in the treatment of osteomyelitis: Results of the Göztepe retrospective cohort study.

OBJECTIVES: Daptomycin is highly effective against Gram-positive multidrug-resistant bacteria. Publications on daptomycin in osteomyelitis treatment are limited. PATIENTS AND METHODS: In this multicenter retrospective cohort study, the aim was to evaluate the outcomes of osteomyelitis cases having received daptomycin or teicoplanin. This multicenter retrospective cohort study gathered data from seven centers located in five cities of Turkey. Study inclusion criteria were as follows: (a) magnetic resonance imaging and/or direct X-ray revealed osteomyelitis or biopsy pathologic examination results concomitant with osteomyelitis. Chi-squareand Student t-tests were used for statistical comparison. RESULTS: A total of 72 patients, 38 cases in the daptomycin group and 34 cases in the teicoplanin group diagnosed with osteomyelitis fulfilling the study inclusion criteria, were included in the study. Clinical success at the end of induction therapy was achieved in 32/38 cases in the daptomycin cohort vs. 30/34 cases in the teicoplanin cohort (p: 0.73). CONCLUSION: Although this is a limited experience in a small but well-defined cohort, our data suggest that daptomycin may be a safe alternative to glycopeptides in osteomyelitis treatment. A randomized controlled clinical study involving larger cohorts may increase the available evidence.

CD8+ T-cell percentage increases in diffuse large B-cell lymphoma patients receiving mannatide combined with standard regimens.

WHAT IS KNOWN AND OBJECTIVE: Suppression of antilymphoma effector cells, mainly T cells, is a key prerequisite for tumorigenesis and resistance in diffuse large B-cell lymphoma (DLBCL). The aim of the study was to determine whether mannatide (MT), an immunomodulator, could enhance the immunological response in DLBCL patients receiving standard regimens. METHODS: Patients with aggressive DLBCL treated with first-line standard regimens were included in this single-centre retrospective study. T-cell subtypes were detected using flow cytometry before and after the first cycle of treatment. Patients in MT group were treated with MT combined with standard first-line regimens, and patients in control group with standard first-line regimens. Chi-square test or Fisher's exact tests were used for categorical variables and independent t-tests for continuous variables. RESULTS AND DISCUSSION: Among the 138 DLBCL patients enrolled in this study, 34 (24.64%) were assigned to the MT group, while 104 (75.36%) patients were included in the control group. There were no significant differences in clinicopathological characteristics and baseline T-cell subtypes between the two groups (p > 0.05). After treatment, CD3+ CD8+ T-cell percentage of MT group was significantly higher than that of control group (p = 0.01), while CD3+ CD4+ T-cell percentage of MT group was significantly lower than that of control group (p < 0.01). Thus, the CD4+ /CD8+ ratio of MT group was significantly lower than that of control group (p = 0.03). In the subgroup of DLBCL patients treated with EPOCH/R-EPOCH, significant differences were also found in post-treatment CD3+ CD8+ T-cell percentage (p < 0.01), CD3+ CD4+ T-cell percentage (p = 0.02) and CD4+ /CD8+ ratio (p = 0.01) between MT and control groups. WHAT IS NEW AND CONCLUSION: CD3+ CD8+ T-cell percentage increased in DLBCL patients receiving MT treatment. Further studies are required to determine the clinical benefits of MT.