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Highlights from the 53rd ICAAC
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Highlights from the 53rd ICAAC Ammara Mushtaq and John McConnell report from the 53rd annual Inter-science Conference on Antimicrobial Agents and Chemotherapy (ICAAC) For the ICAAC website see http://icaac.org/ For conference abstracts see http://www.abstractsonline. com/plan/start. aspx?mkey=%7b7DD36E8852C3-4FF1-A5DF1D00766558B8%7d
Escherichia coli—a common yet complex problem
In a keynote session, Fernando Baquero (University Hospital Ramón y Cajal, Spain) highlighted the fact that our knowledge about antimicrobial agents—in terms of their biochemistry, evolution, genetics, and pathogenesis— has increased exponentially over recent years, but this advance has not been matched by the development of new antimicrobial drugs. Describing this growth in knowledge that we have been unable to translate from bench to bedside, Baquero added that our dilemma today is not necessarily a lack of potential drugs, but rather a lack of research on the usefulness of candidate therapies. He also advocated innovative approaches in combating infections that do not necessarily focus on eliminating pathogens themselves, but include methods such as anticlonal vaccinations, reverse antibiotics, and microbiota modulation. He concluded saying that there are many potential compounds that have been investigated and our future efforts should be directed to giving therapeutic meaning to those drugs.
James Johnson (University of Minnesota, MN, USA) primarily discussed extraintestinal pathogenic Escherichia coli (or ExPEC as their group call it) that typically belong to group B2 of the E coli, which has historically been susceptible to antimicrobial drugs. However, the ST131 serotype, first reported in 2008 by multiple groups, is extensively antimicrobial resistant—fluoroquinolone resistance is, in fact, the hallmark of ST131. On the basis of published medical literature, Johnson postulated that the success of ST131 could be a result of transmissibility (in households or from farms), colonisation fitness, virulence, and antimicrobial resistance.
Alex Bartel/Science Photo Library
Ammara Mushtaq presented the Pakistan session on the Chennai Declaration
Antimicrobial therapy for the future
ICAAC was held Sept 10–13, 2013, in Denver, CO, USA
920
Research and development in developing countries Trevor Mundel (Global Health Programme, Bill & Melinda Gates Foundation), pointed out that infrastructure and human resources in developing countries do not fully support sophisticated scientific initiatives. Therefore, to see success in infectious diseases, different strategies to those used in developed countries are needed. Mundel acknowledged that although we have seen clear success in these countries in the control of communicable diseases, this is still not true for everywhere; in sub-Saharan Africa, for example, “it remains the fact that communicable diseases are virtually just as disappointing now as they were in 1990”, said Mundel. Giving a vision of global health from the perspective of the Gates Foundation, he said that to positively affect health care to a larger degree, in a cost-efficient way, it is important to make rational investments with the resources we have. He mentioned that the two global
programmes in which the foundation is particularly interested are pneumonia and enteric diseases. He added that baseline data are needed to introduce the right interventions, and that such data are scarce. Mundel concluded with an invitation to scientists worldwide to engage with the Foundation to work on ideas that can be helpful in saving lives and improving quality of life in resource-poor countries.
The Chennai Declaration Speaking on the Chennai Declaration, Abdul Ghafur (Apollo Hospital, Chennai, India; C2-897), emphasised the importance of involving clinicians and scientists from developing countries in tackling the issue of antibiotic resistance because “more than two-thirds of the world’s population comes from these countries, and it is not possible to win this battle without them on board”. Mark Toleman (Cardiff University, Cardiff UK; abstr C2-901) reported that among sewage samples from Dhaka, Bangladesh, 62% contained blaNDM and 70% blaCTX-M-15. On further analysing blaNDM positive isolates, Klebsiella pneumoniae isolates had a marked diversity of blaNDM-1 positive plasmids, often with multiple NDM-1 plasmids in individual strains, and some carried the gene on the chromosome. Furthermore, in a study done in the largest tertiarycare hospital of Pakistan (Civil Hospital Karachi, Pakistan, C2-902), 286 (48·6%) of 588 patients had carried blaNDM in rectal samples at admission, with a further acquisition during hospital stay of 7·6 per 100 admissions.
Clostridium difficile in US hospitals Between 2001 and 2010 the incidence of Clostridium difficile infections (CDIs) in adults in US hospitals increased from 4·5 to 8·2 cases per
www.thelancet.com/infection Vol 13 November 2013
Newsdesk
1000 hospital admissions (K-327). C difficile is the leading cause of bacterial infectious diarrhoea in hospitals and is associated with excessive use of antibiotics. The data for Kelly Daniels and colleagues’ (University of Texas, TX, USA) study came from the US Centers for Disease Control and Prevention’s National Hospital Discharge Surveys. The study population consisted of 2·2 million patients with CDI, with a median age of 75 years. Overall mortality for the whole study period was 7·1%, and varied from 8·7% in 2003 to 5·6% in 2009. Median length of hospital stay for CDI patients was 8 days and did not vary over the study period.
New drugs to treat skin infections Results of trials of new antibiotics to treat acute bacterial skin and skin-structure infections (ABSSSIs) caused by Gram positive bacteria were reported in several abstracts. Dalbavancin (Zeven, Durata Therapeutics, Branford, CT, USA) is a lipoglycopeptide that can be given intravenously once per week. In the DISCOVER 1 (L-201) and DISCOVER 2 (L-202) phase 3 trials, Helen Boucher (Tufts Medical Center, Boston, MA, USA) and colleagues and Mark Wilcox (Leeds Teaching Hospital, Leeds, UK) randomly assigned adult patients with ABSSSI to receive intravenous dalbavancin or vancomycin, with the option to switch to oral linezolid in those assigned vancomycin. DISCOVER 1 had about 285 patients in each treatment group, and DISCOVER 2 had about 370 patients. The endpoints of early response to treatment (DISCOVER 1, 83·3% for dalbavancin, 81·8% for vancomycin or linezolid; DISCOVER 2, 76·8% for dalbavancin and 78·3% for vancomycin or linezolid) and clinical status at end of treatment (DISCOVER 1, 87·0% for dalbavancin, 91·4% for vancomycin or linezolid; DISCOVER 2, 93·5% for dalbavancin and 92·7%for
vancomycin or linezolid) were similar between treatment groups. Dalbavancin was associated with low rates of adverse events. The authors conclude that dalbavancin is noninferior to vancomycin or linezolid and could offer an alternative treatment for skin infections. Oritavancin (The Medicines Company, Parsippany, NJ, USA), another lipoglycopeptide antibiotic, also seems at least as affective as vancomycin for the treatment of adults with ABSSSI. A phase 3 trial (SOLO I; L-204) of a single intravenous dose of oritavancin versus 7–10 days of intravenous vancomycin was reported by Ralph Corey and colleagues (Duke Clinical Research Institute, Durham, NC, USA). 475 patients were allocated to the oritavancin group and 479 to vancomycin. Early response to treatment (82·3% for oritavancin, 78·9% for vancomycin) and posttreatment clinical status (79·6% for oritavancin, 80·0% for vancomycin) did not differ between study groups, demonstrating the non-inferiority of oritavancin. Adverse events were either reported less frequently with oritavancin or were similar between the two groups. ESTABLISH 1 and ESTABLISH 2 are phase 3 trials (L-203) of tedizolid (Trius Therapeutics, San Diego, CA, USA) versus linezolid, both of which are oxazolidinone drugs. In the first study, patients with ABSSSI received oral treatment with either antibiotic, whereas in the second study, patients started on intravenous treatment with the option to switch to oral. Carisa De Anda (Trius Therapeutics) and colleagues report that in the two studies combined, 664 patients were analysed in the tedizolid group and 669 in the linezolid group. Tedizolid was non-inferior to linezolid in terms of early response to treatment (81·6% for tedizolid, 79·4% for linezolid) and response at the end of treatment (87·0% for tedizolid, 87·9% for linezolid). Adverse event rates were similar for the two drugs.
www.thelancet.com/infection Vol 13 November 2013
Vitamin D for otitis media Susanna Esposito and colleagues (University degli Studi di Milano, Milan, Italy) investigated whether vitamin D supplementation would reduce the occurrence of acute otitis media (AOM) in children (G-1249). In a randomised trial, 116 children with a history of recurrent AOM were allocated to receive either oral vitamin D supplementation (1000 IU per day) or placebo for 4 months, with episodes of AOM monitored for 6 months. Significantly fewer children in the vitamin D group than in the control group experienced one of more episodes of AOM (26 vs 38, p=0·03). Serum vitamin D concentrations of 30 ng/mL or more were significantly associated with a reduction in episodes of AOM.
Erectile dysfunction drugs and syphilis Nimish Patel (Albany College of Pharmacy and Health Sciences, Albany, NY, USA) and colleagues investigated whether there was an association between use of drugs for erectile dysfunction and a history of syphilis among HIV positive men. Their cross-sectional study used data extracted from the health records of HIV positive adult men attending the Albany Medical Center from 2007–10. 872 men were included in the study, of whom 76 (8·7%) had a recorded diagnosis of syphilis and 131 (15%) had a prescription for an erectile dysfunction drug. In a multivariate analysis that adjusted for age and any use of recreational drugs, use of a drug for erectile dysfunction was associated with syphilis (adjusted odds ratio 1·98, 95% CI 1·11–3·55, p=0·02). The authors caution that it was not always possible to establish whether erectile dysfunction drug use occurred before or after the diagnosis of syphilis, and that they have not established a cause-andeffect relation.
Ammara Mushtaq, John McConnell 921
Highlights from the 53rd ICAAC Ammara Mushtaq and John McConnell report from the 53rd annual Inter-science Conference on Antimicrobial Agents and Chemotherapy (ICAAC) For the ICAAC website see http://icaac.org/ For conference abstracts see http://www.abstractsonline. com/plan/start. aspx?mkey=%7b7DD36E8852C3-4FF1-A5DF1D00766558B8%7d
Escherichia coli—a common yet complex problem
In a keynote session, Fernando Baquero (University Hospital Ramón y Cajal, Spain) highlighted the fact that our knowledge about antimicrobial agents—in terms of their biochemistry, evolution, genetics, and pathogenesis— has increased exponentially over recent years, but this advance has not been matched by the development of new antimicrobial drugs. Describing this growth in knowledge that we have been unable to translate from bench to bedside, Baquero added that our dilemma today is not necessarily a lack of potential drugs, but rather a lack of research on the usefulness of candidate therapies. He also advocated innovative approaches in combating infections that do not necessarily focus on eliminating pathogens themselves, but include methods such as anticlonal vaccinations, reverse antibiotics, and microbiota modulation. He concluded saying that there are many potential compounds that have been investigated and our future efforts should be directed to giving therapeutic meaning to those drugs.
James Johnson (University of Minnesota, MN, USA) primarily discussed extraintestinal pathogenic Escherichia coli (or ExPEC as their group call it) that typically belong to group B2 of the E coli, which has historically been susceptible to antimicrobial drugs. However, the ST131 serotype, first reported in 2008 by multiple groups, is extensively antimicrobial resistant—fluoroquinolone resistance is, in fact, the hallmark of ST131. On the basis of published medical literature, Johnson postulated that the success of ST131 could be a result of transmissibility (in households or from farms), colonisation fitness, virulence, and antimicrobial resistance.
Alex Bartel/Science Photo Library
Ammara Mushtaq presented the Pakistan session on the Chennai Declaration
Antimicrobial therapy for the future
ICAAC was held Sept 10–13, 2013, in Denver, CO, USA
920
Research and development in developing countries Trevor Mundel (Global Health Programme, Bill & Melinda Gates Foundation), pointed out that infrastructure and human resources in developing countries do not fully support sophisticated scientific initiatives. Therefore, to see success in infectious diseases, different strategies to those used in developed countries are needed. Mundel acknowledged that although we have seen clear success in these countries in the control of communicable diseases, this is still not true for everywhere; in sub-Saharan Africa, for example, “it remains the fact that communicable diseases are virtually just as disappointing now as they were in 1990”, said Mundel. Giving a vision of global health from the perspective of the Gates Foundation, he said that to positively affect health care to a larger degree, in a cost-efficient way, it is important to make rational investments with the resources we have. He mentioned that the two global
programmes in which the foundation is particularly interested are pneumonia and enteric diseases. He added that baseline data are needed to introduce the right interventions, and that such data are scarce. Mundel concluded with an invitation to scientists worldwide to engage with the Foundation to work on ideas that can be helpful in saving lives and improving quality of life in resource-poor countries.
The Chennai Declaration Speaking on the Chennai Declaration, Abdul Ghafur (Apollo Hospital, Chennai, India; C2-897), emphasised the importance of involving clinicians and scientists from developing countries in tackling the issue of antibiotic resistance because “more than two-thirds of the world’s population comes from these countries, and it is not possible to win this battle without them on board”. Mark Toleman (Cardiff University, Cardiff UK; abstr C2-901) reported that among sewage samples from Dhaka, Bangladesh, 62% contained blaNDM and 70% blaCTX-M-15. On further analysing blaNDM positive isolates, Klebsiella pneumoniae isolates had a marked diversity of blaNDM-1 positive plasmids, often with multiple NDM-1 plasmids in individual strains, and some carried the gene on the chromosome. Furthermore, in a study done in the largest tertiarycare hospital of Pakistan (Civil Hospital Karachi, Pakistan, C2-902), 286 (48·6%) of 588 patients had carried blaNDM in rectal samples at admission, with a further acquisition during hospital stay of 7·6 per 100 admissions.
Clostridium difficile in US hospitals Between 2001 and 2010 the incidence of Clostridium difficile infections (CDIs) in adults in US hospitals increased from 4·5 to 8·2 cases per
www.thelancet.com/infection Vol 13 November 2013
Newsdesk
1000 hospital admissions (K-327). C difficile is the leading cause of bacterial infectious diarrhoea in hospitals and is associated with excessive use of antibiotics. The data for Kelly Daniels and colleagues’ (University of Texas, TX, USA) study came from the US Centers for Disease Control and Prevention’s National Hospital Discharge Surveys. The study population consisted of 2·2 million patients with CDI, with a median age of 75 years. Overall mortality for the whole study period was 7·1%, and varied from 8·7% in 2003 to 5·6% in 2009. Median length of hospital stay for CDI patients was 8 days and did not vary over the study period.
New drugs to treat skin infections Results of trials of new antibiotics to treat acute bacterial skin and skin-structure infections (ABSSSIs) caused by Gram positive bacteria were reported in several abstracts. Dalbavancin (Zeven, Durata Therapeutics, Branford, CT, USA) is a lipoglycopeptide that can be given intravenously once per week. In the DISCOVER 1 (L-201) and DISCOVER 2 (L-202) phase 3 trials, Helen Boucher (Tufts Medical Center, Boston, MA, USA) and colleagues and Mark Wilcox (Leeds Teaching Hospital, Leeds, UK) randomly assigned adult patients with ABSSSI to receive intravenous dalbavancin or vancomycin, with the option to switch to oral linezolid in those assigned vancomycin. DISCOVER 1 had about 285 patients in each treatment group, and DISCOVER 2 had about 370 patients. The endpoints of early response to treatment (DISCOVER 1, 83·3% for dalbavancin, 81·8% for vancomycin or linezolid; DISCOVER 2, 76·8% for dalbavancin and 78·3% for vancomycin or linezolid) and clinical status at end of treatment (DISCOVER 1, 87·0% for dalbavancin, 91·4% for vancomycin or linezolid; DISCOVER 2, 93·5% for dalbavancin and 92·7%for
vancomycin or linezolid) were similar between treatment groups. Dalbavancin was associated with low rates of adverse events. The authors conclude that dalbavancin is noninferior to vancomycin or linezolid and could offer an alternative treatment for skin infections. Oritavancin (The Medicines Company, Parsippany, NJ, USA), another lipoglycopeptide antibiotic, also seems at least as affective as vancomycin for the treatment of adults with ABSSSI. A phase 3 trial (SOLO I; L-204) of a single intravenous dose of oritavancin versus 7–10 days of intravenous vancomycin was reported by Ralph Corey and colleagues (Duke Clinical Research Institute, Durham, NC, USA). 475 patients were allocated to the oritavancin group and 479 to vancomycin. Early response to treatment (82·3% for oritavancin, 78·9% for vancomycin) and posttreatment clinical status (79·6% for oritavancin, 80·0% for vancomycin) did not differ between study groups, demonstrating the non-inferiority of oritavancin. Adverse events were either reported less frequently with oritavancin or were similar between the two groups. ESTABLISH 1 and ESTABLISH 2 are phase 3 trials (L-203) of tedizolid (Trius Therapeutics, San Diego, CA, USA) versus linezolid, both of which are oxazolidinone drugs. In the first study, patients with ABSSSI received oral treatment with either antibiotic, whereas in the second study, patients started on intravenous treatment with the option to switch to oral. Carisa De Anda (Trius Therapeutics) and colleagues report that in the two studies combined, 664 patients were analysed in the tedizolid group and 669 in the linezolid group. Tedizolid was non-inferior to linezolid in terms of early response to treatment (81·6% for tedizolid, 79·4% for linezolid) and response at the end of treatment (87·0% for tedizolid, 87·9% for linezolid). Adverse event rates were similar for the two drugs.
www.thelancet.com/infection Vol 13 November 2013
Vitamin D for otitis media Susanna Esposito and colleagues (University degli Studi di Milano, Milan, Italy) investigated whether vitamin D supplementation would reduce the occurrence of acute otitis media (AOM) in children (G-1249). In a randomised trial, 116 children with a history of recurrent AOM were allocated to receive either oral vitamin D supplementation (1000 IU per day) or placebo for 4 months, with episodes of AOM monitored for 6 months. Significantly fewer children in the vitamin D group than in the control group experienced one of more episodes of AOM (26 vs 38, p=0·03). Serum vitamin D concentrations of 30 ng/mL or more were significantly associated with a reduction in episodes of AOM.
Erectile dysfunction drugs and syphilis Nimish Patel (Albany College of Pharmacy and Health Sciences, Albany, NY, USA) and colleagues investigated whether there was an association between use of drugs for erectile dysfunction and a history of syphilis among HIV positive men. Their cross-sectional study used data extracted from the health records of HIV positive adult men attending the Albany Medical Center from 2007–10. 872 men were included in the study, of whom 76 (8·7%) had a recorded diagnosis of syphilis and 131 (15%) had a prescription for an erectile dysfunction drug. In a multivariate analysis that adjusted for age and any use of recreational drugs, use of a drug for erectile dysfunction was associated with syphilis (adjusted odds ratio 1·98, 95% CI 1·11–3·55, p=0·02). The authors caution that it was not always possible to establish whether erectile dysfunction drug use occurred before or after the diagnosis of syphilis, and that they have not established a cause-andeffect relation.
Ammara Mushtaq, John McConnell 921