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Journal Roundup

      We're increasingly used to hearing about losing the therapeutic utility of antibiotics due to resistance, so it's good to hear that antibiotics have won the Longitude Prize following a public vote!
      • Rees M.A.
      Longitude prize for the twenty-first century.
      The £10m Longitude Prize will be awarded, following a competitive scheme, to a research group to prompt innovation in the development of novel bacterial diagnostics. However, novel diagnostics is only one of the strategies needing development as we come towards the end of antibiotics. Discussion in the Lancet ID has focused on the need for a global response to the global problem of antibiotic resistance following the recent report from the Lancet Infectious Diseases Commission.
      • Aiken A.M.
      • Allegranzi B.
      • Scott J.A.
      • Mehtar S.
      • Pittet D.
      • Grundmann H.
      Antibiotic resistance needs global solutions.
      • Laxminarayan R.
      • Duse A.
      • Wattal C.
      • et al.
      Antibiotic resistance – the need for global solutions.
      Novel antibiotics are another important need. Randomized controlled studies in the New England Journal of Medicine (NEJM) evaluated two new glycopeptide antibiotics for treating bacterial skin infection.
      • Corey G.R.
      • Kabler H.
      • Mehra P.
      • et al.
      Single-dose oritavancin in the treatment of acute bacterial skin infections.
      • Boucher H.W.
      • Wilcox M.
      • Talbot G.H.
      • Puttagunta S.
      • Das A.F.
      • Dunne M.W.
      Once-weekly dalbavancin versus daily conventional therapy for skin infection.
      A single intravenous dose of oritavancin was non-inferior to twice daily intravenous vancomycin over seven to 10 days.
      • Corey G.R.
      • Kabler H.
      • Mehra P.
      • et al.
      Single-dose oritavancin in the treatment of acute bacterial skin infections.
      Similarly, one weekly intravenous dose of dalbavancin was non-inferior to daily vancomycin followed by linezolid.
      • Boucher H.W.
      • Wilcox M.
      • Talbot G.H.
      • Puttagunta S.
      • Das A.F.
      • Dunne M.W.
      Once-weekly dalbavancin versus daily conventional therapy for skin infection.
      Clearly, a single or weekly dose of antibiotics is preferable for a number of reasons, not least the patient's convenience! The discovery of truly novel antibiotics is limited by the fact that most potential bacterial targets are covered by other agents. A new insight into the construction of the outer membrane lipopolysaccharide published in Nature could spur novel drug discovery.
      • Dong H.
      • Xiang Q.
      • Gu Y.
      • et al.
      Structural basis for outer membrane lipopolysaccharide insertion.
      Another approach is to augment the activity of existing antibiotics. Research in the Journal of Antimicrobial Chemotherapy reports that the addition of an anthracycline antibiotic isolated from Streptomyces sensitized Gram-negative bacteria to the activity of rifampicin.
      • Cox G.
      • Koteva K.
      • Wright G.D.
      An unusual class of anthracyclines potentiate Gram-positive antibiotics in intrinsically resistant Gram-negative bacteria.
      A related approach is the interruption of quorum sensing between bacteria to attenuate virulence. A study in PLoS Pathogens demonstrates that a ‘small molecular inhibitor’ (savirin) selectively inhibits agr-based quorum sensing in Staphylococcus aureus without disrupting Staphylococcus epidermidis.
      • Sully E.K.
      • Malachowa N.
      • Elmore B.O.
      • et al.
      Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance.
      Using chemicals for prophylaxis and treatment of wounds reduces the burden of antibiotic use. A randomized controlled trial in Infection Control and Hospital Epidemiology (ICHE) found that surgical site infection was no more common when using nasal povidone-iodine vs nasal mupirocin prophylaxis.
      • Phillips M.
      • Rosenberg A.
      • Shopsin B.
      • et al.
      Preventing surgical site infections: a randomized, open-label trial of nasal mupirocin ointment and nasal povidone-iodine solution.
      A study in Journal of Infectious Diseases demonstrated that antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii was effective in a mouse burn model and may be a future option for prophylaxis and treatment of burns.
      • Zhang Y.
      • Zhu Y.
      • Gupta A.
      • et al.
      Antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model: implications for prophylaxis and treatment of combat-related wound infections.
      Several studies have identified unnerving levels of antibiotics in effluent from pharmaceutical factories in developing markets such as India.
      • Carlsson G.
      • Orn S.
      • Larsson D.G.
      Effluent from bulk drug production is toxic to aquatic vertebrates.
      However, a study of river sediments in the Midlands of the UK published in the Journal of Antimicrobial Chemotherapy reports that the important ESBL CTX-M-15 gene is being introduced by waste water treatment plants.
      • Amos G.C.
      • Hawkey P.M.
      • Gaze W.H.
      • Wellington E.M.
      Waste water effluent contributes to the dissemination of CTX-M-15 in the natural environment.
      Furthermore, the study reports a carbapenem-resistant Escherichia coli isolate from the river samples. Similar data have also been reported recently from France.
      • Brechet C.
      • Plantin J.
      • Sauget M.
      • et al.
      Wastewater treatment plants release large amounts of extended-spectrum beta-lactamase-producing Escherichia coli into the environment.
      We need to stop polluting our planet with antibiotics!
      The way that antibiotics are prescribed can also affect levels of resistance. A US study found that lower availability of primary care doctors was associated with more inappropriate prescription of antibiotics for upper respiratory tract infections, suggesting that busy doctors are more likely to prescribe antibiotics as the ‘easy way out’.
      • Li P.
      • Metlay J.P.
      • Marcus S.C.
      • Doshi J.A.
      Factors associated with antimicrobial drug use in Medicaid programs.
      To ‘rotate or not to rotate’ empiric antibiotics remains a controversial question. A PLoS Medicine review and meta-analysis concludes that cycling (rotating) antibiotics is associated with a reduction in both infection and resistant infections.
      • Abel Zur Wiesch P.
      • Kouyos R.
      • Abel S.
      • Viechtbauer W.
      • Bonhoeffer S.
      Cycling empirical antibiotic therapy in hospitals: meta-analysis and models.
      Similarly, a review and meta-analysis of antibiotic stewardship to reduce C. difficile incidence yielded a positive outcome.
      • Feazel L.M.
      • Malhotra A.
      • Perencevich E.N.
      • Kaboli P.
      • Diekema D.J.
      • Schweizer M.L.
      Effect of antibiotic stewardship programmes on Clostridium difficile incidence: a systematic review and meta-analysis.
      The World Cup in Brazil and the upcoming Hajj in Saudi Arabia illustrate the challenges of communicable disease identification and control during international events. Lessons from previous events such as the London 2012 Olympics and the Euro 2012 Football Championships in Poland/Ukraine can be applied to current and future gatherings, according to experts commenting in the Lancet and Lancet Infectious Diseases (ID).
      • Memish Z.A.
      • Zumla A.
      • Alhakeem R.F.
      • et al.
      Hajj: infectious disease surveillance and control.
      • McCloskey B.
      • Endericks T.
      • Catchpole M.
      • et al.
      London 2012 Olympic and Paralympic Games: public health surveillance and epidemiology.
      • Smallwood C.A.
      • Arbuthnott K.G.
      • Banczak-Mysiak B.
      • et al.
      Euro 2012 European Football Championship Finals: planning for a health legacy.
      • Lowe R.
      • Barcellos C.
      • Coelho C.A.
      • et al.
      Dengue outlook for the World Cup in Brazil: an early warning model framework driven by real-time seasonal climate forecasts.
      International collaboration is crucial, but the recent ‘discovery’ of an additional 113 MERS-CoV cases raises questions about the transparency of reporting, which could be significant come Hajj time.
      • Dyer O.
      Saudi Arabia reveals 113 previously undisclosed cases of Middle Eastern respiratory syndrome.
      The update of the ‘Compendium of strategies to prevent healthcare-associated infection’ continues in ICHE, with the publication of revised guidelines for central line-associated bloodstream infection and meticillin-resistant S. aureus.
      • Marschall J.
      • Mermel L.A.
      • Fakih M.
      • et al.
      Strategies to prevent central line-associated bloodstream infections in acute care hospitals: 2014 update.
      • Calfee D.P.
      • Salgado C.D.
      • Milstone A.M.
      • et al.
      Strategies to prevent methicillin-resistant Staphylococcus aureus transmission and infection in acute care hospitals: 2014 update.
      The accompanying editorial raises some questions about whether a ‘vertical’ (i.e. targeted) or ‘horizontal’ (i.e. universal) approach is the way to go, reporting a shift in opinion away towards so-called ‘horizontal’ approaches.
      • Septimus E.
      • Weinstein R.A.
      • Perl T.M.
      • Goldman D.A.
      • Yokoe D.S.
      Approaches for preventing healthcare-associated infections: go long or go wide?.
      In support of a move away from pathogen-based ‘vertical’ (targeted) strategies, a Canadian study reported that relaxation of vancomycin-resistant enterococci (VRE) screening and isolation did not affect the rate of VRE infections, although the rate of colonization rose sharply.
      • Popiel K.Y.
      • Miller M.A.
      Evaluation of vancomycin-resistant enterococci (VRE)-associated morbidity following relaxation of VRE screening and isolation precautions in a tertiary care hospital.
      Meanwhile, a dramatic increase in VRE prevalence is reported in a multicentre German study.
      • Gastmeier P.
      • Schroder C.
      • Behnke M.
      • Meyer E.
      • Geffers C.
      Dramatic increase in vancomycin-resistant enterococci in Germany.
      However, a very much ‘vertical’ (targeted) approach has reduced carbapenem-resistant Enterobacteriaceae in Israeli post-acute care hospitals.
      • Ben-David D.
      • Masarwa S.
      • Adler A.
      • Mishali H.
      • Carmeli Y.
      • Schwaber M.J.
      A national intervention to prevent the spread of carbapenem-resistant Enterobacteriaceae in Israeli post-acute care hospitals.
      We need to embrace new technology continually to improve patient outcomes. Even in resource-limited settings, most patients have a mobile phone so it's no surprise that issuing mobile phone reminders improved attendance to scheduled HIV appointments in Cameroon in a Lancet ID randomized controlled trial.
      • Bigna J.J.
      • Noubiap J.J.
      • Kouanfack C.
      • Plottel C.S.
      • Koulla-Shiro S.
      Effect of mobile phone reminders on follow-up medical care of children exposed to or infected with HIV in Cameroon (MORE CARE): a multicentre, single-blind, factorial, randomised controlled trial.
      A ‘big brother is watching’ study in US operating rooms identified a dismal hand hygiene compliance rate for anesthesiologists: 2.9%!
      • Rowlands J.
      • Yeager M.P.
      • Beach M.
      • Patel H.M.
      • Huysman B.C.
      • Loftus R.W.
      Video observation to map hand contact and bacterial transmission in operating rooms.
      The authors, understandably, question the attainability of the hand hygiene recommendations in this setting.
      Several useful reviews have been published recently. The Journal of the American Medical Association (JAMA) has published some handy advice for those tasked with writing editorials.
      • Fontanarosa P.B.
      Editorial matters: guidelines for writing effective editorials.
      NEJM includes a comprehensive review of infections in pregnancy.
      • Kourtis A.P.
      • Read J.S.
      • Jamieson D.J.
      Pregnancy and infection.
      Colistin and polymyxin B are often mentioned in the same breath, but how similar are they? A Clinical Infectious Diseases review likens them to peas in a pod. And chalk and cheese!
      • Nation R.L.
      • Velkov T.
      • Li J.
      Colistin and polymyxin B: peas in a pod, or chalk and cheese?.
      The need for rapid nucleic acid diagnostics is reviewed in Journal of Antimicrobial Chemotherapy.
      • Tuite N.
      • Reddington K.
      • Barry T.
      • Zumla A.
      • Enne V.
      Rapid nucleic acid diagnostics for the detection of antimicrobial resistance in Gram-negative bacteria: is it time for a paradigm shift?.
      However, a JAMA research letter suggests that three-quarters of doctors can't calculate a positive predictive value correctly!
      • Manrai A.K.
      • Bhatia G.
      • Strymish J.
      • Kohane I.S.
      • Jain S.H.
      Medicine's uncomfortable relationship with math: calculating positive predictive value.
      A Journal of Hospital Infection review highlights a potential and largely unrecognized role for free-living amoebae to provide a safe-haven for hospital pathogens such as Legionella pneumophila, Acinetobacter baumannii, and some viruses in hospital water systems.
      • Cateau E.
      • Delafont V.
      • Hechard Y.
      • Rodier M.H.
      Free-living amoebae: what part do they play in healthcare-associated infections?.
      In terms of conferences, the British Society for Antimicrobial Chemotherapy (BSAC) will hold a series of roundtable meetings about antimicrobial resistance in late 2014/early 2015.
      And finally, a Journal of Antimicrobial Chemotherapy study found that UK Chief Medical Officer announcements about antibiotic resistance, and the release of the US Centers for Disease Control and Prevention ‘Antimicrobial Resistance Threat Report’ made Twitter light up in discussion about antibiotics more than any other!
      • Dyar O.J.
      • Castro-Sanchez E.
      • Holmes A.H.
      What makes people talk about antibiotics on social media? A retrospective analysis of Twitter use.

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