Durable viral suppression in an HIV-infected patient in the absence of antiretroviral therapy.

We describe the case of a young woman with an acute HIV infection characterized at onset by neurological features. The patient spontaneously controlled her HIV infection and recovered in a short period of time. The patient's clinical and virological history showed a peculiar evolution of HIV infection, with an MDR HIV-1 in CSF and a wild HIV strain in PBMCs. The patient's PBMC showed a rapid shift from a wild type to an MDR strain in few days.

Comparative efficacy of topical versus systemic teicoplanin in experimental model of wound infections.

INTRODUCTION: Surgical site infections are the second most common cause of nosocomial infections and, typically, gram-positive pathogens are involved. MATERIALS AND METHODS: A mouse model was used to investigate the efficacy of different methods for the treatment of wound infections. A full thickness wound was established on the back subcutaneous tissue of adult male BALB/c mice. A small gauze was placed over each wound and then inoculated with 5 x 10(7) colony-forming units of Staphylococcus aureus. The study included a control group that did not receive any treatment and four contaminated groups treated, respectively, with: (1) drug-free Allevyn (Smith and Nephew Healthcare, Yorkshire, United Kingdom), (2) teicoplanin-soaked Allevyn, (3) drug-free Allevyn and daily intraperitoneal teicoplanin (7 mg/kg) and, finally, (4) teicoplanin-soaked Allevyn and daily intraperitoneal teicoplanin (7 mg/kg). Main outcome measures were quantitative bacterial culture, assessment of vascular endothelial growth factor (VEGF) plasma levels, histological examination with assessment of microvessel density, and of VEGF expression in tissue sections. RESULTS: Data analysis showed that strong inhibition of bacterial growth was achieved in any group treated with intraperitoneal teicoplanin. However, the highest inhibition of bacterial growth was obtained in the group that received teicoplanin-soaked Allevyn and intraperitoneal teicoplanin. Histological examination showed that each treatment modality was able to reduce the delay in wound repair. The most effective treatment appeared to be the local application of teicoplanin-soaked hydro gel foam. The tissue effects were associated with an increase in neovascularization and VEGF expression by endothelial cells and fibroblasts in the granulation tissue. Bacterial colonies also were reduced, especially when teicoplanin was given parenterally. CONCLUSIONS: Soaking a hydro cellular foam with an antistaphylococcal agents, such as teicoplanin, may be useful for the management of infected wounds.

Pretreatment with the protegrin IB-367 affects Gram-positive biofilm and enhances the therapeutic efficacy of linezolid in animal models of central venous catheter infection.

BACKGROUND: Biofilms play an important role in the pathogenesis of several chronic infections and nosocomial infections related to indwelling medical devices. METHODS: To assess the efficacy of IB-367 and linezolid (LZD) in the treatment of central venous catheter (CVC) infections using the antibiotic-lock technique, in vitro and in vivo studies were performed. The in vitro antibiotic susceptibility assay for Staphylococcus aureus and Enterococcus faecalis biofilms developed on 96-well polystyrene tissue culture plates was performed to determine the activity of the compounds. Efficacy studies were performed in rat models of Gram-positive CVC infection. Silastic catheters were implanted into the superior cava of adult male Wistar rats. Twenty-four hours after implantation, the catheters were pretreated by filling with IB-367. Thirty minutes later, rats were challenged via the CVC with 1.0 x 10(6) CFU (colony forming units) of S aureus strain diffuse Smith and clinical isolate of slime-producing E faecalis. Administration of LZD into the CVC at a concentration equal to the minimum bacteriocidal concentration observed using adherent cells or at a much higher concentration (1024 microg/mL) began 24 hours later. RESULTS: Both for S aureus and E faecalis, the killing activities of LZD against adherent bacteria were at least 4-fold to 8-fold lower than that against freely growing cells. For both strains, in IB-367-pretreated wells, LZD strongly increases its activity. The in vivo studies showed that when CVCs were pretreated with IB-367, Gram-positive biofilm bacterial load was further decreased to 10(1) CFU/mL and bacteremia was not detected. CONCLUSIONS: IB-367 has potential as an adjunctive agent to LZD in the treatment of Gram-positive biofilm infections such as CVC infections.

PCR real time assays for the early detection of BKV-DNA in immunocompromised patients.

Testing for viral BKV-DNA in urine is a non-invasive early detection and monitoring tool in the diagnostic of BKV-related pathologies: quantitative analysis by Real-Time PCR can provide useful information in addition to cytologic analysis, although our study suggests that high BKV viruria is not necessarily associated with kidney or bladder damage.

In vitro activities of tachyplesin III against Pseudomonas aeruginosa.

The in vitro activities of tachyplesin III were investigated against 20 multidrug-resistant Pseudomonas aeruginosa clinical isolates. Methods included minimal inhibitory concentrations, minimal bactericidal concentrations, time-kill studies, checkerboard titration method, endotoxin-binding activity and cytotoxicity assay. Overall the organisms were susceptible to the peptide at concentrations of 0.50-4 mg/l. Tachyplesin III completely inhibits the endotoxin procoagulant activity at 22.36 mg/l concentration. Fractional inhibitory concentration indexes demonstrated synergy between the peptide and betalactams or colistin. In conclusion, the intrinsic antibacterial and antiendotoxin activities and the synergistic interactions demonstrated with clinically used antibiotics make tachyplesin III valuable as potential candidate for new therapeutic strategies aimed to treat P. aeruginosa infection.

In vitro activity of aurein 1.2 alone and in combination with antibiotics against gram-positive nosocomial cocci.

This study was performed to evaluate the in vitro activity of the amphibian peptide aurein 1.2 and to investigate its interaction with six antibiotics against nosocomial gram-positive cocci. All isolates were inhibited at concentrations of 1 to 16 mg/liter. Synergy was demonstrated when aurein 1.2 was combined with clarithromycin and minocycline.

In vitro activities of the lipopeptides palmitoyl (Pal)-Lys-Lys-NH(2) and Pal-Lys-Lys alone and in combination with antimicrobial agents against multiresistant gram-positive cocci.

The in vitro activities of the lipopeptides palmitoyl (Pal)-Lys-Lys-NH(2) and Pal-Lys-Lys against gram-positive cocci were investigated. Enterococci and streptococci demonstrated higher susceptibilities than staphylococci and Rhodococcus equi. A positive interaction was shown when the lipopeptides were combined with beta-lactams and vancomycin. These results suggest that lipopeptides are promising candidates for antimicrobial therapy for infections caused by gram-positive organisms.

Distinctin improves the efficacies of glycopeptides and betalactams against staphylococcal biofilm in an experimental model of central venous catheter infection.

The ability of microorganisms to adhere to medical implants is a problem of high visibility and has been focused in numerous investigations. To assess the efficacy of distinctin and conventional antibiotics in the treatment of central venous catheter in vitro and in vivo studies were performed. The in vitro susceptibility assay was performed against S. aureus biofilms developed on 96-well polystyrene tissue culture plates. Efficacy studies were performed in a rat model of CVC infection. Twenty-four hours after implantation, the catheters were filled with distinctin. Thirty minutes later, rats were challenged via the CVC with S. aureus. Administration of antibiotics into the CVC at a concentration equal to the MBC for adherent cells, or at 1024 microg/mL began 24 h later. The killing activities of all antibiotics against adherent bacteria were at least four- to eightfold lower than against freely growing cells. When antibiotics were used in distinctin pretreated wells, they showed a significant increase of activity. The in vivo studies showed that when CVCs were pretreated with distinctin biofilm bacterial load was further decreased to 10(1) CFU/mL and bacteremia was not detected. Distinctin displays potential as an adjunctive agent to antibiotics in the treatment of CVC-related infections.

The cathelicidin-derived tritrpticin enhances the efficacy of ertapenem in experimental rat models of septic shock.

Sepsis remains a serious clinical problem despite intense efforts to improve survival. In this study, the efficacy of ertapenem combined with the cathelicidin tritrpticin was investigated in two rat models of septic shock. Main outcome measures were bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; endotoxin, interleukin 6, and tumor necrosis factor alpha concentrations in plasma; and lethality. Adult male Wistar rats were given (1) an intraperitoneal injection of 1 mg Escherichia coli serotype 0111:B4 LPS or (2) intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg tritrpticin, 15 mg/kg ertapenem, and 1 mg/kg tritrpticin combined with 15 mg/kg ertapenem. Each group included 20 animals. All compounds significantly reduced bacterial growth and lethality as compared with saline treatment. Treatment with tritrpticin resulted in significant decrease in plasma endotoxin and cytokine levels, whereas ertapenem exerted opposite effect. The combination between tritrpticin and ertapenem proved to be the most effective treatment in reducing all variables measured. In conclusion, tritrpticin enhances ertapenem efficacy in gram-negative septic shock rat models.

In vitro activities of tritrpticin alone and in combination with other antimicrobial agents against Pseudomonas aeruginosa.

The in vitro activity of the cathelicidin tritrpticin was investigated against multidrug-resistant Pseudomonas aeruginosa. The isolates were susceptible to the peptide at concentrations of 0.50 to 8 mg/liter. Tritrpticin completely inhibits lipopolysaccharide procoagulant activity at a 10 microM concentration. Fractionary inhibitory concentration indexes (0.385, 0.312, and 0.458) demonstrated synergy between the peptide and beta-lactams.

Effects of caspofungin against Candida guilliermondii and Candida parapsilosis.

The in vitro activity of caspofungin (CAS) was investigated against 28 yeast isolates belonging to Candida albicans (n = 5), Candida guilliermondii (n = 10), and Candida parapsilosis (n = 13). CAS MICs obtained by broth dilution and Etest methods clearly showed a rank order of susceptibility to the echinocandin compound with C. albicans > C. parapsilosis > C. guilliermondii. Similarly, time-kill assays performed on selected isolates showed that CAS was fungistatic against C. albicans and C. parapsilosis, while it did not exert any activity against C. guilliermondii. In a murine model of systemic candidiasis, CAS given at doses as low as 1 mg/kg of body weight/day was effective at reducing the kidney burden of mice infected with either C. albicans or C. guilliermondii isolates. Depending on the isolate tested, mice infected with C. parapsilosis responded to CAS given at 1 and/or 5 mg/kg/day. However, the overall CFU reduction for C. guilliermondii and C. parapsilosis was approximately 100-fold less than that for C. albicans. Our study shows that CAS was active in experimental systemic candidiasis due to C. guilliermondii and C. parapsilosis, but this activity required relatively high drug dosages.