Lorenzo Drago

Review of probiotics available to modify gastrointestinal flora

There is evidence that the oral consumption of micro-organisms produces a protective effect on the gut flora. A significant number of studies suggests that probiotics might have beneficial effects on several microbial disorders of the gut, but it is very difficult to define the clinical efficacy of such products. In this review, we report the results of studies on travellers diarrhoea (TD), antibiotic associated diarrhoea (AAD) and acute diarrhoea (AD) in which various probiotic preparations have been used in controlled trials and been shown to have a beneficial therapeutic or prophylactic effect.

In Vitro Antimicrobial Activity of Propolis Dry Extract

Abstract In this study the antibacterial and antifungal properties of propolis, a natural product of bees, have been investigated against different pathogens. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined according to NCCLS standards on 320 strains including Staphylococcus aureus, Group A beta-hemolytic streptococci, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Candida albicans. Time-kill curves were assessed for susceptible microorganisms, testing 0, 0.5, 1, 2, 4 × MIC for propolis, by counting viable bacteria after 0, 3, 6, 24 hours and viable yeasts after 0, 3, 6, 24 and 48 hours. Propolis showed good antimicrobial activity against most of the isolates, particularly S. pneumoniae, H. influenzae and M. catarrhalis, but not against Enterobacteriaceae. Time-kill curves demonstrated bacteriostatic rather than bactericidal activity of propolis, the latter being evident only at high concentrations.

In vitro evaluation of antibiotics' combinations for empirical therapy of suspected methicillin resistant Staphylococcus aureus severe respiratory infections

BackgroundMethicillin resistant Staphylococcus aureus (MRSA) is an increasingly common cause of nosocomial infections, causing severe morbidity and mortality worldwide, and accounting in some hospitals for more than 50% of all S. aureus diseases. Treatment of infections caused by resistant bacterial pathogens mainly relies on two therapeutic modalities: development of new antimicrobials and use of combinations of available antibiotics.Combinations of antibiotics used in the empiric treatment of infections with suspected methicillin resistant Staphylococcus aureus etiology were investigated.MethodsDouble (vancomycin or teicoplanin with either levofloxacin or cefotaxime) and triple (vancomycin or teicoplanin + levofloxacin + one among amikacin, ceftazidime, cefepime, imipenem, piperacillin/tazobactam) combinations were evaluated by means of checkerboard assay and time kill curves. Mutational rates of single and combined drugs at antimicrobial concentrations equal to the resistance breakpoints were also calculated.ResultsVancomycin or teicoplanin + levofloxacin showed synergy in 16/50 and in 9/50 strains respectively, while vancomycin or teicoplanin + cefotaxime resulted synergic for 43/50 and 23/50 strains, respectively. Triple combinations, involving teicoplanin, levofloxacin and ceftazidime or piperacillin/tazobactam gave synergy in 20/25 strains. Teicoplanin + levofloxacin gave synergy in triple combinations more frequently than vancomycin + levofloxacin.For single antibiotics, mutational frequencies ranged between 10-5 and <10-9 for levofloxacin, cefotaxime, amikacin and imipenem, and <10-9 for vancomycin and teicoplanin. When tested in combinations, mutational frequencies fell below 10-9 for all the combinations.ConclusionIn vitro evidence of synergy between glycopeptides, fluoroquinolones (levofloxacin) and β-lactams and of reduction of mutational frequencies by combinations are suggestive for a potential role in empirical therapy of severe pneumonia with suspected MRSA etiology.

Probiotics reduce gut microbial translocation and improve adult atopic dermatitis.

Background: It has been suggested that probiotics modulate atopic dermatitis (AD) progression, but no data are actually available on their mechanisms of action and on their ability to act as immunomodulators in this pathology. Objective: The aim of this randomized double-blinded active treatment versus placebo study was to evaluate clinical efficacy of an intake of a combination of 2 probiotics (Lactobacillus salivarius LS01 and Bifidobacterium breve BR03) for the treatment of adult AD patients. Methods: Forty-eight patients were enrolled in the study (randomization ratio 2:1) and treated with a combination (LS01 and BR03) or placebo (maltodextrin) for 12 weeks. Clinical efficacy was assessed from baseline by changes in the SCORAD index and DLQ index improvement. Analysis on the gut permeability barrier, immunologic parameters, and changes in fecal microbiota and recovery of probiotics were performed at baseline, at the end of therapy, and 2 months later. Results: Patients receiving probiotics showed a significant improvement in clinical parameters (SCORAD, P<0.0001 and DLQ index, P=0.021) from baseline. The probiotics reduced microbial translocation (P=0.050), immune activation (P<0.001), improved T-helper cell (Th)17/regulatory T cell (Treg) (P=0.029) and Th1/Th2 (P=0.028) ratios. None of these changes were observed in the placebo group. Conclusions: Our results suggest that this specific mixture of probiotics (LS01 and BR03 strains) may induce beneficial effects for clinical and immunologic alterations in adult AD. This combination could be considered as adjuvant therapy for the treatment of AD in adult patients.

Antimicrobial activity of pure platelet-rich plasma against microorganisms isolated from oral cavity

BackgroundAutologous platelet concentrates (PCs) have been extensively used in a variety of medical fields to promote soft and hard tissue regeneration. The significance behind their use lies in the abundance of growth factors in platelets α-granules that promotes wound healing. In addition, antibacterial properties of PCs against various bacteria have been recently pointed out. In this study, the antimicrobial effect of pure platelet-rich plasma (P-PRP) was evaluated against oral cavity microorganisms such as Enterococcus faecalis, Candida albicans, Streptococcus agalactiae, Streptococcus oralis and Pseudomonas aeruginosa. Blood samples were obtained from 17 patients who underwent oral surgery procedures involving the use of P-PRP. The antibacterial activity of P-PRP, evaluated as the minimum inhibitory concentration (MIC), was determined through the microdilution twofold serial method.ResultsP-PRP inhibited the growth of Enterococcus faecalis, Candida albicans, Streptococcus agalactiae and Streptococcus oralis, but not of Pseudomonas aeruginosa strains.ConclusionsP-PRP is a potentially useful substance in the fight against postoperative infections. This might represent a valuable property in adjunct to the enhancement of tissue regeneration.

Antibacterial coating of implants in orthopaedics and trauma: a classification proposal in an evolving panorama

Implanted biomaterials play a key role in current success of orthopedic and trauma surgery. However, implant-related infections remain among the leading reasons for failure with high economical and social associated costs. According to the current knowledge, probably the most critical pathogenic event in the development of implant-related infection is biofilm formation, which starts immediately after bacterial adhesion on an implant and effectively protects the microorganisms from the immune system and systemic antibiotics. A rationale, modern prevention of biomaterial-associated infections should then specifically focus on inhibition of both bacterial adhesion and biofilm formation. Nonetheless, currently available prophylactic measures, although partially effective in reducing surgical site infections, are not based on the pathogenesis of biofilm-related infections and unacceptable high rates of septic complications, especially in high-risk patients and procedures, are still reported.In the last decade, several studies have investigated the ability of implant surface modifications to minimize bacterial adhesion, inhibit biofilm formation, and provide effective bacterial killing to protect implanted biomaterials, even if there still is a great discrepancy between proposed and clinically implemented strategies and a lack of a common language to evaluate them.To move a step forward towards a more systematic approach in this promising but complicated field, here we provide a detailed overview and an original classification of the various technologies under study or already in the market. We may distinguish the following: 1. Passive surface finishing/modification (PSM): passive coatings that do not release bactericidal agents to the surrounding tissues, but are aimed at preventing or reducing bacterial adhesion through surface chemistry and/or structure modifications; 2. Active surface finishing/modification (ASM): active coatings that feature pharmacologically active pre-incorporated bactericidal agents; and 3. Local carriers or coatings (LCC): local antibacterial carriers or coatings, biodegradable or not, applied at the time of the surgical procedure, immediately prior or at the same time of the implant and around it. Classifying different technologies may be useful in order to better compare different solutions, to improve the design of validation tests and, hopefully, to improve and speed up the regulatory process in this rapidly evolving field.

Effects of Lactobacillus salivarius LS01 (DSM 22775) treatment on adult atopic dermatitis: a randomized placebo-controlled study.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by xerosis, pruritus and eczema. The role of probiotics in the prevention and the treatment of AD have been extensively studied in children with controversial results while there are few studies on an adult population. The aim of this randomized, double-blind, placebo-controlled study is to evaluate the clinical efficacy of the intake of a probiotic strain (Lactobacillus salivarius LS01) in the treatment of adult patients with AD. A group of 38 patients was treated with probiotics or placebo (maltodextrin) for 16 weeks. The study was performed from January (T0) to May, 2009 (T16). The assessment of efficacy was based on change in SCORAD (SCORing Atopic Dermatitis) index, dermatology life quality index (DLQI) improvement, cytokine production by PBMCs and ability to modify faecal microbial flora. No significant adverse events were recorded during the study. Patients treated with probiotics showed a statistically improvement of both clinical parameters (SCORAD p< 0.0001 and DLQI p= 0.021) at the end of treatment (T16) compared with the placebo group. Furthermore, after four months of treatment there was a significant reduction of Th1 cytokines (IL-12+IFNγ) (p= 0.03) and Th1/Th2 ratio (IL-12+IFNγ/IL-4+IL-5) (p= 0.019) only in placebo-treated patients. A statistically relevant decrease of staphylococci in faeces of the probiotic-treated group was also observed at the end of treatment. In our study, the administration of L. salivarius LS01 was well tolerated and was associated with a significant improvement of clinical manifestation and QoL. This probiotic strain could have an important role in modulating Th1/Th2 cytokine profiles and could be considered as an important adjunctive therapy in the treatment of adult AD.

A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded calcium-based bone substitutes in the treatment of chronic osteomyelitis: a retrospective comparative study

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed. In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups. After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate. Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Antibiofilm agents and implant-related infections in orthopaedics: where are we?

Abstract Orthopaedics is currently the largest market of biomaterials worldwide and implant-related infections, although relatively rare, remain among the first reasons for joint arthroplasty and osteosynthesis failure. Bacteria start implant infection by adhering to biomaterials and producing biofilms, which represent a major reason for bacterial persistence, in spite of antibiotic treatment and host’s defence. In the last two decades, a number of different antibiofilm agents have been studied and both in vitro and in vivo results appear now promising, even if their effective role in orthopaedics remains to be assessed. In this review, we introduce an original classification of antibiofilm agents, based on their mechanism of action and examine the available data concerning their possible application to orthopaedic implant-related infections. Molecules that interfere with biofilm production (biofilm prevention agents) include anti-adhesion compounds, quorum sensing inhibitors, non-steroideal anti-inflammatory drugs, and antimicrobial peptides; N-acetylcysteine and specific enzymes promise the greatest therapeutic possibilities by disrupting established biofilms (biofilm disrupting agents). The identification of antimicrobials able to bypass the biofilm barrier (biofilm bypassing agents), and antibiofilm vaccines are further strategies aimed to reduce the impact of biofilm-related infections, opening new pathways in controlling implant-related infections. However, this review shows that still insufficient knowledge is currently available as to regard the efficacy and safety of the investigated antibiofilm strategies to treat infection that involve bone tissue and biomaterials commonly implanted in orthopaedics, pointing out the need for further research in this promising field.

Bone and joint infections in adults: a comprehensive classification proposal

Introduction and methodsTen currently available classifications were tested for their ability to describe a continuous cohort of 300 adult patients affected by bone and joint infections. Each classification only focused, on the average, on 1.3 ± 0.4 features of a single clinical condition (osteomyelitis, implant-related infections, or septic arthritis), being able to classify 34.8 ± 24.7% of the patients, while a comprehensive classification system could describe all the patients considered in the study.Result and conclusionA comprehensive classification system permits more accurate classification of bone and joint infections in adults than any single classification available and may serve for didactic, scientific, and clinical purposes.