Abstract:
:Topical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard has in vitro activity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival; P < 0.001) against high-dose (10(6)-PFU) HSV-2 vaginal or rectal challenge. In contrast, zinc acetate formulated in HEC (hydroxyethylcellulose; or the Universal Placebo) failed to protect mice against the high-dose vaginal HSV-2 challenge (similar to aqueous zinc acetate solution and the placebo controls). The gels were found to be effective spreading gels, exhibited limited toxicity in vitro, caused minimal damage to the architecture of the cervicovaginal and rectal mucosae in vivo, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Fernández-Romero JA,Abraham CJ,Rodriguez A,Kizima L,Jean-Pierre N,Menon R,Begay O,Seidor S,Ford BE,Gil PI,Peters J,Katz D,Robbiani M,Zydowsky TMdoi
10.1128/AAC.05461-11subject
Has Abstractpub_date
2012-01-01 00:00:00pages
358-68issue
1eissn
0066-4804issn
1098-6596pii
AAC.05461-11journal_volume
56pub_type
杂志文章abstract::Six tetraoxanes had 50% inhibitory concentrations in the range of 10 to 100 ng/ml against Plasmodium falciparum, whereas the corresponding hexaoxonanes had minimal antimalarial activity. The lack of iron-mediated reactivity of the hexaoxonanes may explain their low activity compared to the tetraoxanes, the latter of w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00264-07
更新日期:2007-08-01 00:00:00
abstract::Fortimicins are bicyclic aminoglycoside antibiotics that contain a fortamine moiety instead of the deoxystreptamine found in other aminoglysides. Fortimicin A had a bactericidal effect on Escherichia coli and Staphylococcus epidermidis and was found to inhibit protein synthesis in vivo. In vitro, fortimicin A inhibite...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.6.857
更新日期:1984-12-01 00:00:00
abstract::The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infect...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.7.1356
更新日期:1991-07-01 00:00:00
abstract::Pseudomonas aeruginosa is equipped with the Sec and Tat protein secretion systems, which translocate the xenobiotic transporter MexAB-OprM and the pathogenic factor phospholipase C (PlcH), respectively. When the signal sequence of MexA was replaced with that of PlcH, the hybrid protein was successfully expressed and r...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01495-09
更新日期:2010-04-01 00:00:00
abstract::An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here we report the identification and characterization of two novel zinc-attenuating compounds, Z...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02024-17
更新日期:2018-04-26 00:00:00
abstract::Monophenol monooxygenase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase EC 1.14.18.1) was studied in melanin-positive and melanin-negative mutants of Streptomyces lincolnensis NCIB 9413, varying in the lincomycin synthesizing ability. The activities of laccase and tyrosine phenol lyase (EC 4.1.99.2) are abs...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.5.526
更新日期:1975-11-01 00:00:00
abstract::Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to human gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in the prevention of H. pylori infection. Experiments were performed to eva...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.8.1895
更新日期:1998-08-01 00:00:00
abstract::The emergence of pneumococci resistant to penicillin and other agents prompted us to evaluate intravenous vancomycin for the therapy of pneumococcal meningitis, which has an overall mortality of 30%. Eleven consecutive adult patients with cerebrospinal fluid (CSF)-culture-proven pneumococcal meningitis and positive in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.35.12.2467
更新日期:1991-12-01 00:00:00
abstract::The in vitro susceptibilities of 12 strains of Chlamydia pneumoniae to a new quinolone, trovafloxacin, and ofloxacin, doxycycline, erythromycin, and azithromycin were determined. The activity of trovafloxacin was similar to that of ofloxacin, with a MIC at which 90% of the isolates are inhibited and a minimal concentr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.9.2033
更新日期:1997-09-01 00:00:00
abstract::The bronchial mucosal concentrations of lomefloxacin were determined for specimens obtained by fiber-optic bronchoscopy and compared with simultaneous concentrations in serum. The 23 patients studied were given an oral dose of 400 mg once daily for 4 days to achieve steady-state levels. The median concentration in ser...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.6.1017
更新日期:1990-06-01 00:00:00
abstract::In Escherichia coli the frequency of spontaneous single-step mutation to high levels of resistance to the newer 4-quinolone agent norfloxacin was confirmed to be over 300-fold lower than that to the older agent nalidixic acid. Serial passage on incremental concentrations of drug was necessary to produce mutants highly...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.4.639
更新日期:1986-04-01 00:00:00
abstract::Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we comp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01153-15
更新日期:2015-12-01 00:00:00
abstract::Mycograb (NeuTec Pharma plc) is a human genetically recombinant antibody against fungal heat shock protein 90 (HSP90). Antibody to HSP90 is closely associated with recovery in patients with invasive candidiasis who are receiving amphotericin B (AMB). Using in vitro assays developed for efficacy assessment of chemother...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.7.2208-2216.2003
更新日期:2003-07-01 00:00:00
abstract::Ten penicillinase-producing Neisseria gonorrhoeae (PPNG) strains isolated from 2000 to 2008 were characterized by multilocus sequence typing, multiantigen sequence typing, and plasmid typing. Sequence analysis showed that 8 strains contained a TEM-1 beta-lactamase gene. However, two other genetically distinct PPNG str...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00245-10
更新日期:2010-07-01 00:00:00
abstract::Colistin use has increased in response to the advent of infections caused by multidrug-resistant organisms. It is administered parenterally as an inactive prodrug, colistin methanesulfonate (CMS). Various formulations of CMS and labeling conventions can lead to confusion about colistin dosing, and questions remain abo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00805-15
更新日期:2015-09-01 00:00:00
abstract::Mongrel dogs with ascites created by inferior vena cava ligation were given cephalothin, cephaloridine, cefazolin, and cefamandole to evaluate the effect of protein binding and serum pharmacokinetics on the distribution of cephalosporins into ascitic fluid. Antibiotics were given intramuscularly (15 mg/kg) every 4 h f...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.2.234
更新日期:1978-08-01 00:00:00
abstract::We have developed a new recombinant retroviral system in which a library of infectious molecular clones of human immunodeficiency virus type 1 (HIV-1) is constructed with reverse transcriptase (RT) genes derived from viral RNA sequences in plasma. HIV-1 RT is amplified from plasma HIV-1 RNA by nested RT-PCR and cloned...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.12.2781
更新日期:1997-12-01 00:00:00
abstract::Five R plasmids transferred from Asian strains of Vibrio cholerae all proved to be members of compatibility group C. A non-self-transmissible plasmid, stable in V. cholerae, was mobilized for transfer to Escherichia coli K-12 and found to be unstably inherited in that host. Plasmids of group C and P transferred to a w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.11.4.585
更新日期:1977-04-01 00:00:00
abstract::The effects of 6-amino-2-n-pentylthiobenzothiazole (APB), a new antifungal agent, on ergosterol biosynthesis in Candida albicans and Saccharomyces cerevisiae were studied, using [14C]acetate incorporation. In C. albicans, the inhibition of growth was accompanied by a marked inhibition of acetate incorporation in 4-des...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.7.1538
更新日期:1995-07-01 00:00:00
abstract::The National Committee for Clinical Laboratory Standards has proposed a reference broth macrodilution method for in vitro antifungal susceptibility testing of yeasts (the M27-P method). This method is cumbersome and time-consuming and includes MIC endpoint determination by visual and subjective inspection of growth in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.9.1998
更新日期:1996-09-01 00:00:00
abstract::Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were =6.2 mug/...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.6.824
更新日期:1978-12-01 00:00:00
abstract::Nephrotoxicity was more marked in rats receiving isepamicin at midlight than at middark. And, the once-daily administration at middark induced a lesser degree of nephrotoxicity than the twice-daily injection, which indicates that the once-daily treatment therapy may have potential value in the clinical use of aminogly...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.9.2042
更新日期:1993-09-01 00:00:00
abstract::The effect of SM-1213 [1,2-O-isopropylidene-3-O-3'-(N', N'-dimethylamino-n-propyl)-D-glucofuranose] on the candidastatic and candidacidal capacity of guinea pig peritoneal exudate cells was investigated. Phagocytes treated with SM-1213 demonstrated an enhanced ability to inhibit intracellular hyphal formation and elon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.1.74
更新日期:1984-07-01 00:00:00
abstract::S. aureus combats cell wall antibiotic stress by altered gene expression mediated by various environmental signal sensors. In this study, we examined the transcriptional regulation of trfA, a gene related to mecA of Bacillus subtilis encoding an adaptor protein implicated in multiple roles, notably, proteolysis and ge...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00220-13
更新日期:2013-07-01 00:00:00
abstract::Lamivudine [beta-L-(-)-2',3'-dideoxy-3'-thiacytidine] is a potent inhibitor of hepadnavirus replication and is used both to treat chronic hepatitis B virus (HBV) infections and to prevent reinfection of transplanted livers. Unfortunately, lamivudine-resistant HBV variants do arise during prolonged therapy, indicating ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.6.1936-1942.2003
更新日期:2003-06-01 00:00:00
abstract::The antimicrobial activity of CS-940, a new trifluorinated quinolone drug, was tested against 761 clinical isolates. CS-940 activity against members of the family Enterobacteriaceae was most similar to that of ciprofloxacin and ofloxacin, with a large range of MICs inhibiting 90% of isolates tested (MIC90S) of 0.015 t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.10.2325
更新日期:1995-10-01 00:00:00
abstract::Escherichia coli K-12 cells grown in 1 to 5 mM sodium salicylate (SAL) or acetylsalicylate show increased phenotypic resistance to various antibiotics (J. L. Rosner, Proc. Natl. Acad. Sci. USA 82:8771-8774, 1985), including cephalosporins (this study). To determine whether these effects are caused by a decreased uptak...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.4.412
更新日期:1989-04-01 00:00:00
abstract::A survey carried out in 2005 among members of a healthy population of children living in Bolivia and Peru revealed that fecal carriage of Escherichia coli strains resistant to expanded-spectrum cephalosporins was remarkably increased compared to that observed in the same settings in 2002 (1.7% in 2005 versus 0.1% in 2...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00026-07
更新日期:2007-08-01 00:00:00
abstract::Since beta-lactam antibiotics have concentration-independent killing, bacterial eradication is a function of the time the serum drug concentration remains above the drug's MIC (T > MIC). We compared the serum bactericidal titers (SBTs) of ceftazidime given by continuous infusion (CI) or by intermittent bolus dosing (B...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/AAC.40.1.61
更新日期:1996-01-01 00:00:00
abstract::Phosphonoformate was found to be an inhibitor of the deoxyribonucleic acid polymerase induced by the herpesvirus of turkeys. The apparent inhibition constants were 1 to 3 muM. Phosphonoformate was also able to block the replication in cell culture of Marek's disease herpesvirus, the herpesvirus of turkeys, and herpes ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.2.188
更新日期:1978-02-01 00:00:00