1.
Low Concentrations of Nitric Oxide Modulate Streptococcus pneumoniae Biofilm Metabolism and Antibiotic Tolerance.
Allan, RN, Morgan, S, Brito-Mutunayagam, S, Skipp, P, Feelisch, M, Hayes, SM, Hellier, W, Clarke, SC, Stoodley, P, Burgess, A, et al
Antimicrobial agents and chemotherapy. 2016;(4):2456-66
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Abstract
Streptococcus pneumoniaeis one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because, although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence ofS. pneumoniaein chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesized that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and that higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO did not result inS. pneumoniaebiofilm dispersal. Instead, treatment of bothin vitrobiofilms andex vivoadenoid tissue samples (a reservoir forS. pneumoniaebiofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low-concentration NO, therefore, appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms.
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Management of recurrent cutaneous abscesses during therapy with infliximab.
De Simone, C, Murri, R, Maiorino, A, Venier, A, Caldarola, G
Clinical therapeutics. 2011;(12):1993-6
Abstract
BACKGROUND Infliximab is a chimeric monoclonal antibody, belonging to the class of anti-tumor necrosis factor-α (TNF-α) agents, approved for the treatment of psoriasis and psoriatic arthritis. Drugs of this class are known to be associated with an infective risk, probably because they interfere with inflammatory and immune response at different levels. Although cutaneous Staphylococcus aureus infections seem to be more frequent than any other infection in the course of anti-TNF-α treatment, only a few case reports in the literature deal with this side effect, and, in particular, with its management. OBJECTIVE Our aim was to report a case of recurrent methicillin-sensitive S aureus (MSSA) cutaneous abscesses during therapy with infliximab and successful management. CASE SUMMARY In July 2009, a 53-year-old white woman (weighing 85 kg) affected by psoriasis and psoriatic arthritis was administered infliximab (5 mg/kg IV), based upon clinical appearance and previous unsuccessful treatment with cyclosporine, methotrexate, etanercept, and adalimumab. Three days after the first 3 infusions (at weeks 0, 2, and 6) she complained about the recurrent onset of painful, erythematous, indurated, and pus-draining cutaneous nodules located on her abdomen. The swab always revealed the presence of MSSA, and antibiotic oral therapy with amoxicillin + clavulanic acid (875 + 125 mg BID for 7 days) was established, with complete resolution of the abscesses. Routine laboratory findings were in normal ranges, with the exception of an elevated erythrosedimentation rate and an increased white blood cell count (range, 13,000-15,000/mm(3)) with neutrophilia (range, 75%-80%). HIV infection was ruled out. In agreement with the infectious disease consultant, 1 day before the fourth infusion, a prophylactic antibiotic therapy with amoxicillin + clavulanic acid (875 + 125 mg BID for 5 days) was added to the therapeutic regimen. This treatment schedule was successfully repeated at each following infusion (every 8 weeks), and no recurrence of skin abscesses was observed. The patient provided signed authorization for publication of this case. CONCLUSIONS This case report describes a woman with psoriasis and psoriatic arthritis who developed MSSA skin abscesses after each of the first 3 infliximab infusions, which did not recur for the next 6 infusions after amoxicillin + clavulanic acid was added to her regimen, pre- and 4 days postinfusion. Adequately designed, placebo-controlled, double-blind trials are needed to determine whether such prophylactic antibiotic treatment is well tolerated or effective for this common complication of therapy with anti-TNF-α agents, when withdrawal of the drug is not advisable, as in this case.
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Does adjuvant antibiotic treatment after drainage of anorectal abscess prevent development of anal fistulas? A randomized, placebo-controlled, double-blind, multicenter study.
Sözener, U, Gedik, E, Kessaf Aslar, A, Ergun, H, Halil Elhan, A, Memikoğlu, O, Bulent Erkek, A, Ayhan Kuzu, M
Diseases of the colon and rectum. 2011;(8):923-9
Abstract
BACKGROUND The risk of fistula formation is a major concern after incision and drainage of an anorectal abscess. OBJECTIVE Our objective was to the test the effects of antibiotic treatment on fistula formation after incision and drainage of anorectal abscesses. DESIGN Randomized, placebo-controlled, double-blind study. SETTING Multicenter trial at 3 teaching hospitals in Turkey. PATIENTS Patients who underwent abscess drainage between September 2005 and January 2008 were evaluated for eligibility. Exclusion criteria included penicillin allergy, antimicrobial agent usage before enrolment, other infection, previous anorectal surgery, inflammatory bowel disease, suspicion of Fournier gangrene, secondary and recurrent anorectal abscesses, anal fistula at time of the surgery, immune compromised states, and pregnancy. INTERVENTION Patients were randomly assigned to receive placebo or amoxicillin-clavulanic acid combination treatment for 10 days after abscess drainage. MAIN OUTCOME MEASURES The primary end point was rate of anorectal fistula formation at 1-year follow-up. RESULTS : Of 334 patients assessed for eligibility, 183 entered the study (placebo, 92; antibiotics, 91). Data were available for per-protocol analysis from 151 patients (placebo, 76; antibiotics, 75) with a mean age of 37.6 years; 118 patients (78.1%) were men. Overall, 45 patients (29.8%) developed anal fistulas during 1-year follow-up. Fistula formation occurred in 17 patients (22.4%) in the placebo group and in 28 patients (37.3%) in the antibiotic group (P = .044). Risk of fistula formation was increased in patients with ischiorectal abscess (odds ratio, 7.82) or intersphincteric abscess (odds ratio, 3.35) compared with perianal abscess. CONCLUSION Antibiotic treatment following the drainage of an anorectal abscess has no protective effect regarding risk of fistula formation.