OBJECTIVES: Gram-positive cocci is the main pathogen responsible for early infection after liver transplantation (LT), posing a huge threat to the prognosis of liver transplant recipients. This study aims to analyze the distribution and drug resistance of Gram-positive cocci, the risk factors for infections and efficacy of antibiotics within 2 months after LT, and to guide the prevention and treatment of these infections. METHODS: In this study, data of pathogenic bacteria distribution, drug resistance and therapeutic efficacy were collected from 39 Gram-positive cocci infections among 256 patients who received liver transplantation from donation after citizens' death in the Third Xiangya Hospital of Central South University from January 2019 to July 2022, and risk factors for Gram-positive cocci infection were analyzed. RESULTS: Enterococcus faecium was the dominant pathogenic bacteria (33/51, 64.7%), followed by Enterococcus faecalis (11/51, 21.6%). The most common sites of infection were abdominal cavity/biliary tract (13/256, 5.1%) and urinary tract (10/256, 3.9%). Fifty (98%) of the 51 Gram-positive cocci infections occurred within 1 month after LT. The most sensitive drugs to Gram-positive cocci were teicoplanin, tigecycline, linezolid and vancomycin. Vancomycin was not used in all patients, considering its nephrotoxicity. Vancomycin was not administered to all patients in view of its nephrotoxicity.There was no significant difference between the efficacy of daptomycin and teicoplanin in the prevention of cocci infection (P>0.05). Univariate analysis indicated that preoperative Model for End-Stage Liver Disease (MELD) score >25 (P=0.005), intraoperative red blood cell infusion ≥12 U (P=0.013) and exposure to more than 2 intravenous antibiotics post-LT (P=0.003) were related to Gram-positive cocci infections. Multivariate logistic regression analysis revealed that preoperative MELD score >25 (OR=2.378, 95% CI 1.124 to 5.032, P=0.024) and intraoperative red blood cell transfusion ≥ 12 U (OR=2.757, 95% CI 1.227 to 6.195, P=0.014) were independent risk factors for Gram-positive cocci infections after LT. Postoperative Gram-positive cocci infections were reduced in LT recipients exposing to more than two intravenous antibiotics post-LT (OR=0.269, 95% CI 0.121 to 0.598, P=0.001). CONCLUSIONS Gram-positive cocci infections occurring early after liver transplantation were dominated by Enterococcus faecalis infections at the abdominal/biliary tract and urinary tract. Teicoplanin, tigecycline and linezolid were anti-cocci sensitive drugs. Daptomycin and teicoplanin were equally effective in preventing cocci infections due to Gram-positive cocci. Patients with high preoperative MELD score and massive intraoperative red blood cell transfusion were more likely to suffer Gram-positive cocci infection after surgery. Postoperative Gram-positive cocci infections were reduced in recipients exposing to more than two intravenous antibiotics post-LT.
Humans ; Daptomycin/therapeutic use* ; Linezolid/therapeutic use* ; Teicoplanin/therapeutic use* ; Gram-Positive Cocci ; Liver Transplantation/adverse effects* ; Tigecycline/therapeutic use* ; End Stage Liver Disease/drug therapy* ; Gram-Positive Bacterial Infections/microbiology* ; Severity of Illness Index ; Anti-Bacterial Agents/pharmacology* ; Vancomycin/therapeutic use* ; Microbial Sensitivity Tests

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of healthcare-associated infections. Recently, community-associated MRSA has emerged, manifesting as skin and soft tissue infections in patients without any prior healthcare contact. Vancomycin, a glycopeptide in clinical use for more than 50 years, still remains an acceptable treatment option. However, significant concerns have been raised regarding the decreasing susceptibility of S. aureus to this agent. The growing awareness of the limitations of vancomycin has served as an impetus for development of newer agents. There has been an increase in the number of agents available to treat MRSA infections. Linezolid, daptomycin, telavancin, and ceftaroline have received regulatory approval in the last decade for the treatment of MRSA. Although these drugs do have certain differentiating attributes and may offer some advantages over vancomycin, they also have significant limitations.
Daptomycin ; Delivery of Health Care ; Humans ; Linezolid ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Skin ; Soft Tissue Infections ; Vancomycin

BACKGROUND: To investigate the national molecular epidemiology and resistance profiles of vancomycin-intermediate Staphylococcus aureus (VISA), we analyzed the characteristics of methicillin-resistant Staphylococcus aureus (MRSA) collected from clinical samples at tertiary or general hospitals participating in a nationwide surveillance program for VISA and vancomycin-resistant Staphylococcus aureus (VRSA) in Korea during an 12-week period in each year from 2007 to 2013. METHODS: VISA was defined by agar dilution, broth dilution and E-test methods with vancomycin minimum inhibitory concentrations of >2 μg/mL. All VISA isolates were characterized by multilocus sequence typing, staphylococcal cassette chromosome mec typing, spa typing, accessory gene regulator typing, Diversilab analysis, and antibiogram analysis. RESULTS: Of 109,345 MRSA isolates, 87,354 were screened and 426 isolates were identified as positive on brain heart infusion agar containing 4 μg/mL vancomycin (BHI-V4). Of 426 isolates, 76 isolates were identified as VISA. No VRSA isolates were detected among the isolates. Overall, a total of 6 genotypes were identified among VISA strains and the predominant clones were ST5-II-t2460, ST72-IV-t324, and ST239-III-t037 (44.7%, 15.8%, and 10.5%, respectively). Of note, ST72-IV-t324 clones are known to be a typical community-associated MRSA. ST239-III-t037 strains were more resistant to trimethoprim-sulfamethoxazole than any other type of strain. ST72-IV-t324 strains were susceptible to all of the antimicrobial agents tested except erythromycin and daptomycin. All of the VISA isolates were susceptible to linezolid and quinupristin-dalfopristin. CONCLUSION: Although VRSA is still rare, continuous monitoring of VRSA occurrence is needed, as well as VISA prevalence, epidemic clonal shift, and antimicrobial resistance.
Agar ; Anti-Infective Agents ; Brain ; Clone Cells ; Daptomycin ; Erythromycin ; Genotype ; Heart ; Hospitals, General ; Korea* ; Linezolid ; Methicillin-Resistant Staphylococcus aureus ; Microbial Sensitivity Tests ; Molecular Epidemiology ; Molecular Typing* ; Multilocus Sequence Typing ; Prevalence ; Staphylococcus aureus* ; Staphylococcus* ; Trimethoprim, Sulfamethoxazole Drug Combination ; Vancomycin

Anti-Bacterial Agents ; Daptomycin ; Gram-Positive Bacterial Infections ; Hematologic Diseases ; Humans

In the face of escalating problems with pathogen control, the development of proper formulations of existing antibiotics is as important as the development of novel antibiotics. Daptomycin is a lipopeptide antibiotic with potent activity against Gram-positive bacteria. Currently, only injectable solution of daptomycin has been approved for clinical use. In the present study, the formulation of PEGylated liposomal daptomycin (PLD) was prepared and optimized, and its efficacy against methicillin-resistant Staphylococcus aureus (MRSA252) strains was investigated. The obtained PLD had a mean vesicle diameter of (111.5 +/- 15.4) nm and a mean percent drug loading of (5.81 +/- 0.19) % with high storage stability. Potent activity of PLD against MRSA was demonstrated in vitro with a more sustained effect than that of conventional liposomal daptomycin and daptomycin solution. In addition, intravenous administration of a single dose (equal to human use) of PLD significantly increased the survival of mice in a MRSA252 systemic infection model compared with other formulations. Drug distribution in the lung was significantly enhanced following administration of PLD, and no measurable tissue lesions or pathological changes were detected during PLD treatment. Taken together, PEGylated liposomes loaded with daptomycin may represent a promising approach to reduce MRSA252 infections, especially those involving bloodstream dissemination, such as hematogenous pulmonary infection.
Animals ; Anti-Bacterial Agents ; pharmacology ; Daptomycin ; pharmacology ; Liposomes ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Staphylococcal Infections ; drug therapy

We investigated the antibiotic susceptibility of glycopeptide-resistant enterococci (GRE). Seventy consecutive GRE were tested. Sixty-two isolates were identified as Enterococcus faecium (88.6%), and 8 (11.4%) as Enterococcus faecalis. All strains were susceptible to linezolid and daptomycin, while 17.1% (12/70) and 11.4% (8/70) were resistant to quinupristin/dalfopristin (QD) and tigecycline, respectively. All E. faecalis isolates were resistant to QD, while 4 of 62 (6.5%) E. faecium isolates were resistant to QD. All E. faecalis isolates were susceptible to tigecycline, while 14.5% (9/62) E. faecium isolates were resistant. Continued surveillance of GRE antibiotic susceptibilities is important for combating these multi-resistant nosocomial pathogens.
Daptomycin* ; Enterococcus faecalis ; Enterococcus faecium ; Linezolid ; Teicoplanin

Adolescent ; Adult ; Agranulocytosis ; microbiology ; Anti-Bacterial Agents ; adverse effects ; therapeutic use ; Daptomycin ; adverse effects ; therapeutic use ; Female ; Gram-Positive Bacterial Infections ; drug therapy ; Humans ; Male ; Middle Aged ; Young Adult

Natural cyclopeptides are hot spots in chemical and pharmaceutical fields because of the wide spreading bio-resources, complex molecular structures and various bioactivities. Bio-producers of cyclopeptides distribute over almost every kingdom from bacteria to plants and animals. Many cyclopeptides contain non-coded amino acids and non-pepditic bonds. Most exciting characteristic of cyclopeptides is a range of interesting bioactivities such as antibiotics gramicidin-S (2), vancomycin (3) and daptomycin (4), immunosuppressive cyclosporin-A (1) and astin-C (8), and anti-tumor aplidine (5), RA-V (6) and RA-VII (7). Compounds 1-4 are being used in clinics; compounds 5-8 are in the stages of clinical trial or as a candidate for drug research. In this review, the progress in chemical and bioactive studies on these important natural bioactive cyclopeptides 1-8 are introduced, mainly including discovery, bioactivity, mechanism, QSAR and synthesis.
Animals ; Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; therapeutic use ; Cyclosporine ; chemistry ; pharmacology ; Daptomycin ; chemical synthesis ; chemistry ; pharmacology ; Depsipeptides ; chemical synthesis ; chemistry ; therapeutic use ; Gramicidin ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Immunosuppression ; Immunosuppressive Agents ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Neoplasms ; drug therapy ; Peptides, Cyclic ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Quantitative Structure-Activity Relationship ; Vancomycin ; chemical synthesis ; chemistry ; pharmacology

Daptomycin, a lipopeptide antibiotic with similar action as vancomycin, is used to treat complicated skin and soft tissue infections caused by resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, penicillin-resistant streptococci, and vancomycin-resistant enterococci. Acute generalized exanthematous pustulosis (AGEP), characterized by acute onset of numerous sterile, nonfollicular pinhead sized pustules, is common secondary to drugs, in particular, antibiotics. We present the first case of AGEP following the use of daptomycin.
Acute Generalized Exanthematous Pustulosis ; Anti-Bacterial Agents ; Daptomycin ; Gram-Positive Bacteria ; Methicillin-Resistant Staphylococcus aureus ; Skin ; Soft Tissue Infections ; Vancomycin

There are relatively few novel antimicrobial agents despite the dramatic increase in antimicrobial resistance and multiple drug resistance of clinical isolates worldwide. Vancomycin is still the most widely used antibiotic for treating resistant Gram-positive coccal infections in children, especially for methicillin-resistant Staphylococcus aureus. For children with Gram-positive coccal infections where vancomycin is not effective or older therapeutic agents cannot be tolerated, linezolid, quinupristin-dalfopristin or daptomycin may be useful in the appropriate clinical setting. For Gram-negative infections, new carbapenems await clinical application. Tebipenem pivoxil is a novel oral carbapenem undergoing clinical trials for acute otitis media in pediatric patients. Antiviral drug development is now progressing at the pace of antibiotic development 30 years ago. Newer antiviral agents used for the treatment of herpes viruses and hepatitis C virus infections in children are included in this review.
Acetamides ; Anti-Bacterial Agents ; Anti-Infective Agents ; Antiviral Agents ; Carbapenems ; Child ; Daptomycin ; Drug Resistance, Multiple ; Hepacivirus ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Otitis Media ; Oxazolidinones ; Vancomycin ; Virginiamycin ; Linezolid