Elisa Bertazzoni Minelli

Controlled clinical trial of pefloxacin versus imipenem in severe acute pancreatitis

BACKGROUND & AIMS Antibiotic prophylaxis in severe pancreatitis has recently yielded promising clinical results, with imipenem significantly reducing the incidence of infected necrosis compared with an untreated control group. On the bases of pefloxacins spectrum of action and pancreatic penetration, we investigated whether such drugs represent a valid alternative to imipenem. METHODS In a multicenter study, 60 patients with severe acute pancreatitis with necrosis affecting at least 50% of the pancreas were randomly allocated to receive intravenous treatment for 2 weeks with pefloxacin, 400 mg twice daily (30 patients), or imipenem, 500 mg three times daily (30 patients), within 120 hours of onset of symptoms. Age, sex, body weight, Ranson and Apache II scores, C-reactive protein, etiology, and time from onset of symptoms to treatment were well matched in the two groups. RESULTS The incidences of infected necrosis and extrapancreatic infections were 34% and 44%, respectively, in the pefloxacin group and 10% and 20% in the imipenem group. Imipenem proved significantly more effective in prevention of pancreatic infections (P </= 0.05). Mortality was not significantly different in the two groups. CONCLUSIONS Despite its theoretical potential, pefloxacin is inferior to imipenem in the prevention of infections associated with severe pancreatitis.

Modulation of the Intestinal Ecosystem by Probiotics and Lactulose in Children During Treatment with Ceftriaxone

Abstract Background: The value of oral bacteriotherapy during antibiotic treatment is a much debated subject. Comparative studies on the effects of different probiotics on the intestinal ecosystem are lacking. Objective: Six different commercially available preparations of probiotics and 1 prebiotic (lactulose) were compared to establish whether their action prevented or corrected imbalances in the intestinal ecosystem (dysbiosis) during parenteral therapy with ceftriaxone. Methods: Fifty-one children (25 female, 26 male; mean age, 5.1 years) admitted to the hospital for febrile respiratory tract infections were treated. Ceftriaxone 50 mg/kg per day was administered parenterally alone (therapy 1) or with 1 of the following probiotic/prebiotic preparations: Saccharomyces boulardii (therapy 2); Enterococcus species (therapy 3); lactulose (therapy 4); Lactobacillus casei GG (therapy 5); Lactobacillus rhamnosus, Lactobacillus bifidus , and Lactobacillus acidophilus (therapy 6); Bifidobacterium bifidum and L acidophilus (therapy 7); or a mixture of various lactobacilli and bifidobacteria at high concentrations (therapy 8). Intestinal microflora were evaluated by standard microbiologic methods and by biochemical assays on fecal samples collected before and after treatment. Results: Ceftriaxone induced a decrease in Escherichia coli and lactobacilli counts and an increase in cocci and clostridia counts. Partial protection of the intestinal ecosystem (eubiosis) was achieved with therapies 6, 7, and 8, which contained different combinations of Lactobacillus and Bifidobacterium species. Probiotics containing lactobacilli were more active than the older Saccharomyces and Enterococcus preparations. The newer probiotics reduced β-galactosidase, β-glucosidase, and β-glucuronidase levels. Increased fecal β-lactamase activity was observed in 60% of patients treated with ceftriaxone alone and 75% of those treated with ceftriaxone and S boulardii . A lower incidence of beta-lactamase-positive samples (30%–40%) was observed with therapy 7 and therapy 8. Conclusions: In this preliminary study, probiotics containing multiple species of lactobacilli and bifidobacteria administered at high concentration (20 billion to 360 billion per day) were more effective in preventing dysbiosis induced by ceftriaxone treatment than were other preparations studied. Probiotic therapy may need to be maintained for several days after discontinuation of antibiotic treatment to adequately restore balance to the intestinal ecosystem.

Antimicrobial activity of gentamicin and vancomycin combination in joint fluids after antibiotic-loaded cement spacer implantation in two-stage revision surgery

Abstract Gentamicin (G) and vancomycin (V) concentrations in joints fluids obtained from patients during the first 24 hours after implantation of antibiotic-loaded polymethylmethacrylate (PMMA) spacers in two-stage revision for infected arthroplasty, and the inhibitory activity of joint fluids against different multiresistant clinical isolates were studied. A total of 12 patients undergoing two-stage revision surgery with implantation of industrial G spacers added with different amounts of V was studied. Serum and joint fluid samples were collected 1, 4, and 24 hours after spacer implantation. Antibiotics concentrations and joint bactericidal titer (JBT) of combination were determined against multiresistant staphylococcal strains. The local release of G and V from PMMA cement seemed prompt and effective. Serum levels were below the limit of detection. The same joint fluid showed different activity according to the susceptibility of the pathogens tested. Gentamicin and V were released from spacers at bactericidal concentrations exerting a strong inhibition against methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (CoNS) strains.

Microbiological and pharmacological tests on new antibiotic-loaded PMMA-based composites for the treatment of osteomyelitis

Local antibiotic diffusion in rabbit femurs from two new PMMA‐based and nail‐shaped composites, enriched with β‐tricalcium phosphate (P‐TCP) and BaSO4 or only with BaSO4 (P‐BaSO4), and soaked in a solution of gentamicin (G) and vancomycin (V) was studied. Nails were implanted into the intramedullary cavity of healthy and osteomyelitic femurs to study the resolution of infection and to quantify the antibiotic penetration into bone by microbiological, pharmacological, and histological tests. A significant progression of osteomyelitis was recorded 7 weeks after MRSA inoculation, whereas no bacteria were found in animals treated with antibiotic‐loaded nails as confirmed by microbiology and histology (Smeltzer score). The release of both antibiotics from composites was high and prompt both in healthy and infected bone; the amount of V was higher than that of G in all bone samples. Antibiotics of both composites were still present in bone 3 weeks after nail implantation. The P‐BaSO4 composite released a lower amount of antibiotics than did P‐TCP. The G–V combination in vivo exerted a synergistic bactericidal effect, which was confirmed by microbiological, histological, and clinical results (no infection). These new porous PMMA composites, soaked in G–V solution in the operating room, might be an effective and useful drug delivery system for osteomyelitis treatment.

New PMMA-based composites for preparing spacer devices in prosthetic infections

Even though the systemic antibiotic therapy is usually applied after prosthetic infections surgical treatments, it is unable to reach the infection site in sufficient concentrations to eradicate bacteria. Delivering antibiotics locally with the use of custom made device (spacer or nail coating) might eradicate or reduce the infection and the risk of recolonization, providing a very high concentration of antibiotic. PMMA-based (Mendec Spine®) composites with BaSO4 were enriched with β-tricalcium phosphate (Porosectan-TCP) or only a slightly higher BaSO4 concentration (Porosectan-BaSO4) to obtain higher porosity. The aim of the study was to evaluate: (i) drug absorption capability and drug release kinetics in vitro soaking them with a combined solution of gentamicin and vancomycin, (ii) their in vitro and in vivo biocompatibility, and finally, (iii) they were tested preliminarily in an experimental model of bone infection. The simultaneous presence of β-TCP and BaSO4 resulted in the formation of a texture of interconnecting channels with different diameters, from a few microns to several hundred microns, which totally filled the material. The porosity, determined by microcomputed tomography, was significantly higher in both tested plain composites (Porosectan-TCP: +17.3%; Porosectan-BaSO4: +7.5%) in comparison to control composite material (Mendec Spine®). The kinetics of antibiotic release from composites was rapid and complete, producing high drug concentrations for a short period of time. Both composites showed a good level of biocompatibility. The osteomyelitic model confirmed that both composites, soaked in antibiotic solution, were able to cure bone infection. These composites could be useful for preparing devices for prosthetic joint infections treatment also allowing the use of antibiotics solution at required concentrations.