Daniel V. Lim

Change in antibiotic resistance of group B streptococcus: impact on intrapartum management.

OBJECTIVE Intrapartum chemoprophylaxis has resulted in a significant reduction of group B Streptococcus neonatal infection. For penicillin-allergic patients, clindamycin or erythromycin is the recommended antibiotic. The purpose of this study was to establish any pattern of antibiotic resistance of group B streptococcal clinical isolates over the past 15 years. STUDY DESIGN Group B streptococcal isolates obtained from the lower genital tract were tested for sensitivity to ampicillin, penicillin, clindamycin, and erythromycin. The sensitivity of 100 group B streptococcal isolates retrieved in the period 1997-1998 was compared with that of 85 group B streptococcal isolates from 1980-1993. RESULTS From 1980-1993 group B streptococcal isolates were available for testing for antibiotic resistance along with 100 isolates from a second study period 1997-1998. Of the 100 group B streptococcal isolates from 1997-1998, 18 were resistant to erythromycin, of which 5 were also resistant to clindamycin, as compared with 1 of the 85 isolates from 1980-1993 that was resistant to erythromycin (P <.001). All the isolates were sensitive to ampicillin and penicillin. All 18 resistant strains from 1997-1998 were found to be sensitive to cephalothin. CONCLUSION Over the past 18 years there has been increased in vitro resistance of group B streptococci to both clindamycin and erythromycin. If other studies confirm these findings, modifications to the current Centers for Disease Control and Prevention recommendations may be necessary.

Studies on the antifungal properties of N-thiolated β-lactams

N-thiolated beta-lactams had previously been shown to have antibacterial activity against a narrow selection of pathogenic bacteria including Staphylococcus aureus and Bacillus anthracis, as well as apoptotic-inducing activity in a variety of human cancer cell lines. We now have found that these lactams also possess antifungal activity against Candida and other fungi by exerting powerful cytostatic effects that disrupt the structural integrity of cytoplasmic membranes. The mode of action and structure-activity trends of these lactams as antifungals parallel that previously seen in our antibacterial studies.

Physical Properties and Biological Activity of Poly(butyl acrylate–styrene) Nanoparticle Emulsions Prepared with Conventional and Polymerizable Surfactants

UNLABELLED Recent efforts in our laboratory have explored the use of polyacrylate nanoparticles in aqueous media as stable emulsions for potential applications in treating drug-resistant bacterial infections. These emulsions are made by emulsion polymerization of acrylated antibiotic compounds in a mixture of butyl acrylate and styrene (7:3 wt/wt) using sodium dodecyl sulfate as a surfactant. Prior work in our group established that the emulsions required purification to remove toxicity associated with extraneous surfactant present in the media. This article summarizes our investigations of poly(butyl acrylate-styrene) emulsions made using anionic, cationic, zwitterionic, and noncharged (amphiphilic) surfactants, as well as attachable surfactant monomers (surfmers), comparing the cytotoxicity and microbiological activity levels of the emulsion both before and after purification. Our results show that the attachment of a polymerizable surfmer onto the matrix of the nanoparticle neither improves nor diminishes cytotoxic or antibacterial effects of the emulsion, whether or not the emulsions are purified, and that the optimal properties are associated with the use of the nonionic surfactants versus those carrying anionic, cationic, or zwitterionic charge. Incorporation of an N-thiolated beta-lactam antibacterial agent onto the nanoparticle matrix via covalent attachment endows the emulsion with antibiotic properties against pathogenic bacteria such as methicillin-resistant Staphylococcus aureus, without changing the physical properties of the nanoparticles or their emulsions. FROM THE CLINICAL EDITOR Emulsions of polyacrylate nanoparticles, antibiotics and surfactants were studied using surfactant monomers as controls. Nonionic surfactants resulted in the most optimal properties. Incorporation of a beta-lactam antibacterial agent onto the nanoparticle matrix endowed the emulsion with antibiotic properties against methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of hospital acquired, treatment-resistant infections including sepsis.

N-Thiolated β-Lactam Antibacterials: Defining the Role of Unsaturation in the C4 Side Chain

N-Methylthio beta-lactams represent a novel family of antibacterial agents for methicillin-resistant Staphylococcus aureus (MRSA). The structure-activity functions and mechanism of action of these compounds, although still largely undefined, differ dramatically from those of all previously reported beta-lactam antibiotics. Prior work has established that the N-alkylthio moiety is required for antibacterial activity, and that a variety of unsaturated groups can be tolerated at C(4) of the lactam ring. This report describes the effect that unsaturation within the C(4) substituent has on antibacterial activity of these interesting new N-thiolated beta-lactams.

Effect of aryl ring fluorination on the antibacterial properties of C4 aryl-substituted n-methylthio β-lactams

4-Aryl-substituted N-thiolated beta-lactams are a new family of antibacterial agents possessing unique structure-activity profiles and a mode of action. Unlike traditional beta-lactam antibiotics, which require highly polar enzyme-binding groups, these lactams bear hydrophobic groups on their side chains. In this study, we examine the effect that increasing hydrophobicity, through fluorine substitution in the C(4) aryl ring, has on the antibacterial properties.

DIETARY FATTY ACID (FA) EFFECTS UPON GROUP B STREPTOCOCCAL (GBS) INFECTION. † 1893

Dietary FA effects upon the immune response may be mediated in part by effects upon proinflammatory cytokines and eicosanoids. The impact of maternal diet FA composition upon mortality from GAS infection was studied in neonatal rat pups. Methods: Timed pregnant dams were fed, beginning on day 2 of gest. and throughout lactation, either chow (control) or a purified diet whose fat source (22% of cals) was either corn oil (high n6) or menhaden fish oil (high n3). On day 3 of life, pups were culled to 10 pups per dam and were randomly cross-fostered among dams fed the same diets to minimize litter effects. Milk was removed from culled pup stomachs for FA analysis. Exp 1: On day 7 of life, pups were injected i.p. with 0.1 ml of a suspension of GAS Type I as follows: one litter per diet with 106.5 organisms, and one litter per diet with 107.5 organisms. Data from both doses were combined for statistical analyses. Exp 2: On day 7 of life, pups (n=1 litter per diet group) were injected with 107 GAS organisms and sacrificed 48 hours later. Blood was collected for GAS culture and analysis of serum TNFα levels; spleen weights were determined. Results: FA composition of milk reflected maternal diet (Table). Exp 1: 100% of pups in the chow and corn oil groups died within 96 hours, while 33% survived in the fish oil group (p=0.002 fishers exact (permutation) test). Exp 2: Spleen weights (as% body weight) were significantly higher in the fish vs corn and chow groups. Preliminary cytokine data suggest lower serum levels of TNFα and a trend towards fewer positive blood culture in pups of the fish group. Conclusion: The FA composition pre- and/or postnatal diet may affect immune response to bacterial sepsis. Funded in part by Ross Laboratories.