Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis.

BACKGROUND: Although assemblies of hydrophobic-modified bacitracin A with PLGA (Nano-BAPLGA) have demonstrated promising antibacterial activities against both Gram-positive and Gram-negative bacteria, the desirable antibacterial potency has remained challenging due to the low solubility of Nano-BAPLGA. To address this tissue, a series of Pluronic copolymers (Pluronic® F127, Pluronic® P123 and Pluronic® P85) were selected to link the N-terminus of bacitracin A to construct Pluronic-based nano-self assemblies (Nano-BAF127, Nano-BAP123 and Nano-BAP85). RESULTS: Impressively, all the newly designed Pluronic-based Nano-BAs possessed higher solubility and stronger effectiveness against both Gram-positive and Gram-negative bacteria compared with Nano-BAPLGA, especially the modification with Pluronic® P85. Surface tension measurements indicated that Nano-BAP85 was much more tensioactive than Nano-BAPLGA, which usually translated into a good membranolytic effect. Fluorescence spectroscopy and electron microscopy analyses confirmed the speculation that the cell wall/membrane might be the main action target of Nano-BAP85 by permeabilizing the cell membrane and damaging the membrane integrity. In vivo results further demonstrated that Nano-BAP85 significantly suppressed bacterial growth and prolonged survival time in the bacterial peritonitis mouse model with negligible toxicity. CONCLUSIONS: Collectively, the membrane targeting mechanism of action is entirely distinct from those of clinically used antibacterial agents. Furthermore, the new approach of construction nanoantibiotics based on the modification of commercially available antibiotics with Pluronic copolymers is demonstrated to have an efficient therapeutic effect against bacterial infection.

Dual-Responsive Nanogels with Cascaded Gentamicin Release and Lysosomal Escape to Combat Intracellular Small Colony Variants for Peritonitis and Sepsis Therapies.

Intracellular bacteria are the major cause of serious infections including sepsis and peritonitis, but face great challenges in fighting against the stubborn intracellular small colony variants (SCVs). Herein, the authors have developed nanogels (NGs) to destroy both planktonic bacteria and SCVs and eliminate excessive inflammations for peritonitis and sepsis therapies. Free gentamicin (GEN) and hydroxyapatite nanoparticles (NPs) with GEN loading and mannose grafts (mHAG) are inoculated into ε-polylysine NGs to obtain NG@G1-mHAG2 through crosslinking with phenylboronic acid and tannic acid. The H2O2 consumption after reaction with phenylboronic esters and the elimination of free radicals by tannic acid alleviates the escalated inflammatory status to promote sepsis therapy. After mannose-mediated uptake into macrophages, the acid-triggered degradation of mHAG NPs generates Ca2+ to destabilize lysosomes and the efficient lysosomal escape leads to reversion of hypometabolic SCVs into normal phenotype and their sensitivity to GEN. In a peritonitis mouse model, NG@G1-mHAG2 treatment provides strong and persistent bactericidal effects against both extracellular bacteria and intracellular SCVs and extends survival of peritonitis mice without apparent hepatomegaly, splenomegaly, pulmonary edema, and inflammatory cell infiltration. Thus, this study demonstrates a concise and versatile strategy to eliminate SCVs and relieve inflammatory storms for peritonitis and sepsis therapies without infection recurrence.

Effect of 4% gelofusine plus antibiotics on renal impairment and mortality in high-risk cirrhotic patients with spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) increases the rates of renal impairment and mortality in cirrhotic patients. A previous study showed that cefotaxime plus albumin treatment decreased renal impairment more than antibiotic treatment alone in patients with serum bilirubin > 4 mg/dL or creatinine > 1 mg/dL. 4% Gelofusine is a colloidal volume replacement fluid used for fluid resuscitation and hemodynamic stabilization. Only one study showed that intravenous 4% gelofusine plus antibiotic could decrease the rates of renal impairment and mortality in comparison with the treatment with albumin plus antibiotic in high-risk cirrhotic patients with SBP OBJECTIVE: To evaluate the effects of 4% gelofusine plus antibiotics on renal impairment and mortality rates in high-risk cirrhotic patients with spontaneous bacterial peritonitis. MATERIAL AND METHOD: Eighteen cirrhotic patients with SBP and serum bilirubin > 4 mg/dL or creatinine > 1 mg/dL were enrolled. Ceftriaxone was given intravenously in doses of 2 g/day. Gelofusine 4% was given intravenously at 1.5 g/kg of body weight at the time of the diagnosis, followed by 1 g/kg on the 3 day. Renal impairment and mortality rates were evaluated during and after treatment. RESULTS: Five patients (27.8%) had pre-existing renal failure. Infection resolved in 15 patients (83.3%). Renal impairment developed in three patients (16.7%), and six patients (33.3%) died during hospitalization. After one month, the mortality rate was 33.3% (a total of 6 deaths). Patients with renal impairment had higher levels of plasma renin activity than those without renal impairment but the values were not statistically significant. CONCLUSION: In high-risk cirrhotic patients with spontaneous bacterial peritonitis, treatment with 4% gelofusine intravenously plus antibiotic reduced the incidence of renal impairment but did not reduce mortality in comparison with previous studies. Studies with larger sample sizes may be useful to evaluate these effects.

Antimicrobial-loaded biodegradable nanoemulsions for efficient clearance of intracellular pathogens in bacterial peritonitis.

Intracellular pathogenic bacteria use immune cells as hosts for bacterial replication and reinfection, leading to challenging systemic infections including peritonitis. The spread of multidrug-resistant (MDR) bacteria and the added barrier presented by host cell internalization limit the efficacy of standard antibiotic therapies for treating intracellular infections. We present a non-antibiotic strategy to treat intracellular infections. Antimicrobial phytochemicals were stabilized and delivered by polymer-stabilized biodegradable nanoemulsions (BNEs). BNEs were fabricated using different phytochemicals, with eugenol-loaded BNEs (E-BNEs) affording the best combination of antimicrobial efficacy, macrophage accumulation, and biocompatibility. The positively-charged polymer groups of the E-BNEs bind to the cell surface of macrophages, facilitating the entry of eugenol that then kills the intracellular bacteria without harming the host cells. Confocal imaging and flow cytometry confirmed that this entry occurred mainly via cholesterol-dependent membrane fusion. As eugenol co-localized and interacted with intracellular bacteria, antibacterial efficacy was maintained. E-BNEs reversed the immunosuppressive effects of MRSA on macrophages. Notably, E-BNEs did not elicit resistance selection after multiple exposures of MRSA to sub-therapeutic doses. The E-BNEs were highly effective against a murine model of MRSA-induced peritonitis with better bacterial clearance (99 % bacteria reduction) compared to clinically-employed treatment with vancomycin. Overall, these findings demonstrate the potential of E-BNEs in treating peritonitis and other refractory intracellular infections.

Local imipenem activity against Pseudomonas aeruginosa decreases in vivo in the presence of siliconized latex.

Zinc eluted from siliconized latex (SL) increases resistance of Pseudomonas aeruginosa to imipenem in vitro. A foreign body peritonitis model was used to evaluate the activity of imipenem using SL or silicone (S) implants. No differences were observed in mortality, positive blood cultures and tissue bacterial counts between SL and S implants. Implant-associated counts, however, were significantly higher in the SL group. It is concluded that SL decreases the activity of imipenem against P. aeruginosa.

Implant-induced intraperitoneal inflammatory angiogenesis is attenuated by fluvastatin.

1. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitors, exert anti-inflammatory, anti-oxidant and anti-angiogenic effects. These effects are associated with downregulation of pro-inflammatory/pro-angiogenic molecules and upregulation of endothelial nitric oxide synthase (e-NOS) expression/nitric oxide (NO) production. 2. Using the murine sponge model to induce chronic intraperitoneal inflammatory response, we evaluated the inflammatory components, angiogenic and NO production of the fibrovascular tissue, and their modulation by fluvastatin. 3. Our results showed that fluvastatin (0.6 and 6 mg/kg per day) inhibited haemoglobin (Hb) content 4.9±0.4 (n=15; control) vs 2.2±0.2 (n=6; fluvastatin 0.6) and 1.8±0.2 (n=6; fluvastatin 6.0) and the number of vessels in the treated group when compared with the control group. The inflammatory component, as assessed by myeloperoxidase and N-acetyl-ß-d-glucosaminidase activities and by the pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α) and Monocyte chemotactic protein-1 (MCP-1)/CCL2/JE levels, was also decreased by the compound. In the treated group, inhibition of both enzyme activities was 54% and 57%, respectively. The levels of the cytokines (TNF-α and CCL2/JE) intra-implant were decreased relative to the control. In these implants, fluvastatin was also able to increase NO production, as detected with an NO-sensitive electrode. 4. The inhibitory function of fluvastatin on key components of intraperitoneal inflammatory angiogenesis shown in the present study is clearly associated with the modulatory effects of this statin on vascular endothelial growth factor, TNF-α and NO production.

Peritoneal Dialysis-Related Peritonitis Caused by Streptococcus oralis.

A 77-year-old man developed peritoneal dialysis-related peritonitis caused by Streptococcus oralis, a rare pathogen causing the disease. The infection, which was not controlled by one-week intraperitoneal administration of cefazolin and ceftazidime, was cured only after switching to two-week intravenous administration of cefazolin and ceftazidime. The patient had no major dental disease or recent history of dental intervention. This case suggests that S. oralis might cause peritoneal dialysis-related peritonitis with persistent systemic inflammation via an extra-oral infection route. The clinical course is discussed along with a review of the literature.

ZnO-loaded DNA nanogels as neutrophil extracellular trap-like structures in the treatment of mouse peritonitis.

Neutrophil extracellular traps (NETs) are chromatin-based structures that are released from neutrophils during infections and prevent microbes from spreading in the body through efficient degradation of their composition. Based on this chromatin-driven strategy of capturing and killing bacteria, we designed NET-like structures using DNA and ZnO nanoparticles (NPs). DNA was first purified from kiwifruit and treated with HCl to increase hydroxyl groups in the opened-deoxylribose form. The carboxyl groups of citric acid were then thermally crosslinked with said hydroxyl and primary amine groups in DNA, forming DNA-HCl nanogels (NGs). ZnO NPs were then used as positively charged granule enzymes, adsorbed onto the DNA-HCl NG, obtaining ZnO/DNA-HCl NGs (with NET biomimicry). In an anti-inflammatory assay, ZnO/DNA-HCl NGs significantly inhibited TNF-α, IL-6, iNOS and COX-2 expression in LPS-stimulated Raw264.7 cells. Moreover, the ZnO/DNA-HCl NGs markedly alleviated clinical symptoms in LPS-induced mouse peritonitis. Finally, ZnO/DNA-HCl NGs suppressed E. coli from entering circulation in septic mice while prolonging their survival. Our results suggest that the ZnO/DNA-HCl NGs, which mimic NET-like structures in the blocking of bacteria-inducted inflammation, may be a potential therapeutic strategy for bacterial infections.

Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase.

The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane86.7%, 1,5-pentanediol13.3%)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.

[Efficiency of polyoxidonium in combined therapy in patients with generalized peritonitis].

Emergency abdominal surgery for peritonitis is a topical problem awaiting solution. Disturbed immune status of patients with peritonitis dictates the necessity to supplement postoperative intensive therapy by medical preparation normalizing immune functions. We have studied 36 patients with generalized peritonitis of different etiology of whom 20 (controls) were treated by traditional methods and 16 received standard therapy plus polyoxidomium. The frequency of abdominal and other complications in the latter group decreased to 19.2% and lethality to 13.8% while duration of the hospital stay was reduced by 3.6 patient days.

Tannic acid-based nanogel as an efficient anti-inflammatory agent.

Biologically produced reactive oxygen species (ROS) are important signaling molecules in the human body. Despite their importance under normal conditions, abnormal overproduction of ROS under unbalanced or irregular homeostasis can cause severe inflammatory diseases. Various antioxidants have been developed in the biomedical field to resolve high levels of ROS; however, high doses of natural antioxidants such as polyphenol can induce side effects on health. Further, synthetic antioxidants are still controversial in regards to their safety and their complicated synthesis. Inspired from our previous work, a nitric oxide-scavenging nanogel designed for treating rheumatoid arthritis, we report herein a biocompatible tannic acid (TA)-based nanogel as an effective ROS scavenger. A polymeric phenylboronic acid-tannic acid nanogel (PTNG) was prepared by simply mixing through to the formation of phenylboronic ester bonds between polymeric phenylboronate and TA. We focused on the reaction of phenylboronic ester with H2O2, which readily consumes H2O2 molecules, and applied it as an antioxidant. In addition, TA is a well-known antioxidant, specifically a free radical scavenger; thus, we expected combinatory ROS scavenging effects for PTNG. Various ROS scavenging assays revealed the significant antioxidant effects of PTNG. Under an induced inflammation model in vitro, our PTNG showed high biocompatibility as well as strong anti-inflammatory effects. Furthermore, in the zymosan-induced peritonitis mouse model, a representative acute inflammation model in vivo, PTNG reduced significant neutrophil recruitment and pro-inflammatory cytokines, indicating successful alleviation of inflammation. On the basis of these results, we suggest that PTNG has great potential as an antioxidant and should find application in the treatment of further ROS-overproducing inflammatory diseases.

Tc-99m-PEG-liposomes target both adhesions and abscesses and their reduction by hyaluronate in rats with fecal peritonitis.

BACKGROUND: Abdominal adhesions and abscesses are a major source of morbidity and mortality after abdominal surgery and peritonitis. Adhesions are hard to detect with standard imaging techniques. Liposomes, coated with polyethylene glycol (PEG), represent an agent developed for infection imaging. This study investigated the capacity of 99mTc-PEG-liposomes to localize early adhesion formation after peritonitis. Additionally, the value of 99mTc-PEG-liposomes for therapy evaluation of hyaluronan solution, which reduces adhesion and abscess formation in experimental peritonitis, was assessed. METHODS: In 24 rats, a bacterial peritonitis was induced by performing a cecal ligation and puncture procedure. The animals were treated with sodium chloride solution or 0.4% hyaluronan solution intra-abdominally. One week later, scintigraphy was performed using 99mTc-PEG-liposomes, and abnormal focal uptake in the abdomen was scored. Thereafter, autopsy was performed and adhesions and abscesses were scored. RESULTS: A significant correlation was found between the total adhesion score and the scintigraphic score (P < 0.01, r = 0.65). Treatment with hyaluronan significantly reduced the total adhesion score (P = 0.01). The size of abscesses significantly correlated with the scintigraphic score (P < 0.01, r = 0.65). Treatment with hyaluronan reduced the size of abscesses (P < 0.05). CONCLUSION: 99mTc-PEG-liposomes are able to detect early adhesions and abscesses and may be used for therapy evaluation of agents that reduce adhesions and abscesses.

Compatibility of ciprofloxacin with commercial peritoneal dialysis solutions.

Intraperitoneal administration of antibiotics together with peritoneal dialysis fluids (PDFs) remains the preferable route for treatment of peritoneal dialysis-related peritonitis. For home based therapy, antibiotic-containing PDFs are stored for up to two weeks and warmed up to body-temperature before administration. The present study investigated the compatibility of ciprofloxacin with five commercial PDFs at refrigeration-temperature, room-temperature and body-temperature. Ciprofloxacin concentrations were determined using high-performance liquid chromatography. Drug-diluent stability was evaluated by measurement of pH-values and visual inspection at each sampling point. The antimicrobial activity of ciprofloxacin was assessed by an E. coli disk diffusion method. Ciprofloxacin was stable at refrigeration-temperature and body-temperature in all PDFs evaluated over the whole study period of 14 days and 24 hours, respectively. At room-temperature, in contrast, ciprofloxacin demonstrated only limited stability in particular when tested in mixed Physioneal. Except for Physioneal 1.36%, no relevant drug adsorption was observed and the antimicrobial activity of ciprofloxacin was found to be preserved in each PDF at each storage condition investigated. Intraperitoneal ciprofloxacin might be used for inpatient and home based therapy of peritoneal dialysis-related peritonitis and no compensatory dose adjustment is needed when stored for up to two weeks at refrigeration-temperature before use.

Mucormycosis peritonitis: more than 2 years of disease-free follow-up after posaconazole salvage therapy after failure of liposomal amphotericin B.

A 57-year-old woman with end-stage kidney disease secondary to autosomal dominant polycystic kidney disease developed peritoneal dialysis-related Mucor peritonitis after her pet cockatoo bit through her transfer set. The infection persisted despite more than 8 weeks of treatment with liposomal amphotericin B. On a compassionate basis, she then received oral posaconazole, 800 mg/d, in divided doses for 6 months. She experienced complete remission and has remained disease free since then, for more than 2 years. We review the medical literature about mucormycosis peritonitis which, albeit rare, carries very high mortality. The treatment of choice is liposomal amphotericin B, which failed in our patient. Our case report suggests that posaconazole is an attractive treatment option in patients with peritoneal dialysis-related Mucor peritonitis.

Bioresponsive Nanoparticles Targeted to Infectious Microenvironments for Sepsis Management.

Sepsis is a life-threatening disease resulted from a dysregulated host immune response to bacterial infections, continuing to cause high morbidity and mortality worldwide. Despite discoveries of many potential therapeutic targets, effective treatments of sepsis are lacking. Here, a strategy is reported to target infectious microenvironments (IMEs) via bioresponsive nanoparticles that simultaneously eliminate bacteria and alleviate the host inflammation response, thus managing sepsis in mice. The nanoparticle is made of copolymers sensitive to pH and bacterial enzymes to self-assemble into a micelle loaded with both an antibiotic (ciprofloxacin) and an anti-inflammatory agent ((2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide). In addition, the nanoparticle is conjugated with intercellular adhesion molecule-1 antibodies to target IMEs. Nanoparticle targeting to IMEs and local cues as triggers to deliver therapeutics in on-demand manners is demonstrated using an acute lung bacterial infection mouse model. In the sepsis mouse model induced by peritonitis at a lethal dose of bacterial invasion, it is shown that concurrently targeting pathogens and excessive inflammation pathways is valuable to manage the sepsis. The study illustrates not only the development of a new delivery system but also the mechanism-based therapy of nanomedicine for infectious diseases.

Use of a "composite" vascular access graft in a young child on hemodialysis.

Although arterio-venous fistulae (AVF) are currently considered to be the first choice of permanent vascular access for hemodialysis, there are some patients who are not candidates for fistulae and synthetic grafts provide other options. The Thoratec (Vectra) polyurethane vascular access graft is a new prosthetic graft that may be cannulated within days of insertion due to "self-sealing" properties. However, a tendency for kinking at the suture site due to the strong elasticity of this graft, leading to undesirable complications such as thrombosis, have been reported. We describe a surgical modification of the anastomosis by interposing a segment of expanded polytetrafluoroethylene graft (ePTFE, Venaflo) between the native vessels and the polyurethane graft sections in a pediatric patient. This modification may overcome the kinking complication associated with use of the polyurethane graft and the resulting thrombosis.

Successful treatment of Nocardia asteroides peritonitis in a patient undergoing automated peritoneal dialysis and receiving immunosuppressive therapy.

Nocardiosis is an opportunistic infection especially in patients with underlying chronic debilitating disease or immunodeficiency. Nocardia peritonitis is an uncommon infection in peritoneal dialysis patients. Here, we report a case of peritonitis by Nocardia asteroides during automated peritoneal dialysis in a 35-year-old male patient who had prolonged immunosuppressive therapy to treat acute rejection of a nonfunctioning kidney allograft. The patient presented at our outpatient clinic with typical symptoms of acute peritonitis. The peritoneal fluid leukocyte count was 20,500 cells/microL, with 90% neutrophils. Gram staining showed gram-positive filamentous bacilli later identified as N. asteroides. After bacterial identification, the patient received trimethoprim 320 mg and sulfamethoxazole 3200 mg intravenously every 48 hours (TMP-SMX), plus amikacin 100 mg intraperitoneally daily. The immunosuppressive therapy was reduced. Peritoneal fluid cultures became negative after 1 week of treatment, concomitant with clinical improvement. Unfortunately, after 5 weeks of therapy, the patient developed hematologic side effects attributable to the TMP-SMX treatment. The TMP-SMX was suspended at that time, and the patient then received cefuroxime 500 mg by mouth and amikacin 100 mg intraperitoneally daily for a total of 12 weeks. The patient recovered completely and was discharged 3 months after onset of the peritonitis. Prolonged antibiotic therapy without catheter removal has not been previously described in immunosuppressed patients with APD peritonitis. The combination of amikacin and TMP-SMX may be safe and effective in APD patients who develop N. asteroides peritonitis.

EFFECTS OF TOPICAL TREATMENT WITH EUPHORBIA TIRUCALLI LATEX ON THE SURVIVAL AND INTESTINAL ADHESIONS IN RATS WITH EXPERIMENTAL PERITONITIS.

BACKGROUND: The use of plants of the family Euphorbiaceae, particularly Euphorbia tirucalli (avelós) has been popularly widespread for treating a variety of diseases of infectious, tumoral, and inflammatory. AIM: To demonstrated antimicrobial and immunomodulatory effects of these extracts, evaluating the effect of a topical treatment with an aqueous solution of avelós latex on the survival and on intestinal adhesions in rats with experimental peritonitis. METHODS: Peritonitis was induced in 24 Wistar rats, that were randomized into four groups of six as follows: (1) Control group (n=6), no treatment; (2) Antibiotic group (n=6), treatment with a single intramuscular dose of antibiotic Unasyn; (3) Saline group (n=6), the abdominal cavity was washed with 0.9% saline; and (4) E.tirucalli group (n=6), the abdominal cavity was washed with E. tirucalli at a concentration of 12 mg/ml. The animals that died were necropsied, and the time of death was recorded. The survivors were killed on postoperative day 11, and necropsy was subsequently performed for evaluation of the intestinal adhesions. RESULTS: Significant differences were observed in the control and antibiotic groups (p<0.01) with respect to the survival hours when compared with the saline and E. tirucalli groups. There was no significant difference (p>0.05) in the survival of animals in the saline andE. tirucalli groups; however, one animal died in the saline group. Necropsy of the animals in the saline and E. tirucalligroups showed strong adhesions resistant to manipulation, between the intestinal loops and abdominal wall. The remaining groups did not show any adhesions. CONCLUSIONS: Topical treatment with E. tirucalli latex stimulated an increased formation of intestinal adhesions and prevented the death of all animals with peritonitis.

Antimicrobial evaluation of quaternary ammonium polyethyleneimine nanoparticles against clinical isolates of pathogenic bacteria.

Peritonitis is a disease caused by bacterial strains that have become increasingly resistant to many antibiotics. The development of alternative therapeutic compounds is the focus of extensive research, so novel nanoparticles (NPs) with activity against antibiotic-resistant bacteria should be developed. In this study, the antibacterial activity of quaternary ammonium polyethyleneimine (QA-PEI) NPs was evaluated against Streptococcus viridans, Stenotrophomonas maltophilia and Escherichia coli. To appraise the antibacterial activity, minimal inhibitory concentration (MIC), minimal bactericidal concentration and bactericidal assays were utilised with different concentrations (1.56-100 µg/ml) of QA-PEI NPs. Moreover, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and annexin V/propidium iodide toxicity assays were performed in cell cultures. MICs for S. maltophilia and E. coli isolates were 12.5 and 25 µg/ml, respectively, whereas the MIC for S. viridans was 100 µg/ml. Furthermore, the growth curve assays revealed that these QA-PEI NPs at a concentration of 12.5 µg/ml significantly inhibited bacterial growth for the bacterial isolates studied. On the other hand, QA-PEI NPs lacked significant toxicity for cells when used at concentrations up to 50 µg/ml for 48 h. The present findings reveal the potential therapeutic value of this QA-PEI NPs as alternative antibacterial agents for peritonitis, especially against Gram-negative bacteria.

Enhanced effectiveness of intraperitoneal antibiotics administered via liposomal carrier.

The local application of antibiotics to treat intraperitoneal contamination has been used with variable results. Liposomes are not rapidly absorbed from the peritoneal cavity, offering a potential delivery system for intraperitoneal antibiotics. The effects of liposome-incorporated antibiotic administration in a fecal peritonitis model were compared with the effects of conventional intraperitoneal and intramuscular antibiotics. Rats were divided into four groups: untreated, intramuscular cefoxitin, intraperitoneal cefoxitin, and intraperitoneal liposome-incorporated cefoxitin. Quantitative blood cultures were drawn at 4 and 24 hours. Liposome delivery of cefoxitin significantly reduced mortality and bacteremia at 4 and 24 hours compared with control subjects and conventional antibiotic groups. Peritoneal abscess formation tended to decrease in the liposome antibiotic group (mean +/- SEM, 6.86 +/- 0.79) compared with the group receiving free intraperitoneal administration of antibiotics (10.33 +/- 1.63). We conclude that liposomal delivery significantly enhances the effectiveness of cefoxitin in this model of peritonitis.