MD Conference Express ICAAC 2011 - (Page 27)

and in Phase 3 trials (n=17,622), it had 100% (95% CI, 75 to 100) efficacy [FUTURE II Study Group. J Infect Dis 2007]. The latter protects against types 16 and 18. In a Phase 3 trial (n=16,126), it had 92.9% efficacy (95% CI, 80 to 99) [Paavonen J et al. Lancet 2009]. Figure 2. HPV Genotypes in Cervical Cancer. 16 18 45 31 33 52 71% 17.2 6.7 2.9 2.6 2.3 2.2 1.4 1.3 1.2 1 0.7 0.6 0.5 0.3 1.2 4.4 and Candida albicans, a ubiquitous fungus that is capable of causing invasive disease. P. aeruginosa readily attaches to filamentous C. albicans, creating a biofilm, and together they infect catheters, ventilator tubing, and other devices, as well as eyes, wounds, burns, and the lungs of CF patients. Coinfection can negatively affect patients. A 2010 prospective study in P. aeruginosa-infected CF patients demonstrated a correlation between the advent of C. albicans colonization and an increase in exacerbations [Chotirmall et al. Chest 2010]. On a cellular level, this seeming kinship between P. aeruginosa and C. albicans is actually highly contentious, as it is subject to a kind of interspecies molecular warfare and continual adaptation in the effort to survive. Dr. Hogan highlighted various facets of the relationship, both friendly and antagonistic. P. aeruginosa is able to kill filamentous C. albicans hyphae by secreting a group of toxic small molecules, called phenazines [Peleg et al. Nat Rev Microbiol 2010]. Candida fights back by secreting farnesol, which, in some instances, dismantles P. aeruginosa’s phenazine production [Hornby et al. Appl Environ Microbiol 2001] but, in other instances increases it by bumping up downstream production [Cugini et al. Microbiol 2010]. Farnesol also promotes the conversion of filamentous fungal elements to the more stable yeast morphology, resistant to P. aeruginosa attachment and killing [Westwater et al. Eukaryot Cell 2005; Deveau et al. Eukaryot Cell 2010]. Over time, a chronic coinfection milieu may select for a more synergistically inclined P. aeruginosa variant that demonstrates reduced antifungal capacity (due to defective quorum sensing and phenazine production) but improved growth. However, P. aeruginosa is also armed with a novel, highly toxic 5-methylphenazine, possibly specifically intended for its C. albicans foe, as it is not generally produced by solitary Pseudomonas species. Importantly, microbe-microbe interactions may also impact a host’s ability to clear the infection. Recent data show that the presence of P. aeruginosa may suppress host immune response to C. albicans. In a recent study, single-pathogen infection models with P. aeruginosa and C. albicans produced the expected immune responses in total cell count and cell differential, with P. aeruginosa causing a strong neutrophilic response and C. albicans inducing more of a macrophage and eosinophilic response. However, when the two organisms were combined, the immune response more closely resembled that of P. aeruginosa, as if C. albicans was not present [Allard and Whittaker. Med Mycol 2010]. This suggests that coinfection may allow organisms, such as C. albicans, to evade immune recognition and set up persistent infections in patients. Official Peer-Reviewed Highlights from the 51st ICAAC HPV Genotype 58 35 59 56 51 39 68 73 82 Other X 0 10 20 30 40 50 60 70 80 90 Cancer Cases Attributed to the Most Frequent HPV Genotypes (%) 100 HPV=human papillomavirus. Reproduced with permission from L. Eckert, MD. Why Can’t Microbes Just Get Along? Written by Noelle Lake, MD Deborah Hogan, PhD, Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire, USA, has been hard at work exploring the love-hate relationship between two important pulmonary pathogens that are common among patients with cystic fibrosis (CF). She shared the institution's discoveries and discussed the clinical relevance of microbe-microbe interactions in the State-of-the-Art lecture, “Pseudomonas and Candida: Friends or Foes?” Today, increasing numbers of patients are experiencing multispecies infections, often bacterial-fungus infections, due to greater use of medical devices, transplantation, and other interventions that allow patients to live longer with chronic diseases. Understanding the interplay between coinfecting organisms and how they affect their hosts may lead to refinements in patient management. In the environment, Pseudomonads have a rather fickle relationship to fungi—sometimes synergistic, as with the colonization and protection of the chanterelle mushroom, and sometimes antagonistic. Dr. Hogan’s laboratory is attempting to untangle a similarly convoluted relationship between Pseudomonas aeruginosa, a gramnegative bacterium that is common in soil and hospitals, 27  http://www.mdconferencexpress.com

Table of Contents for the Digital Edition of MD Conference Express ICAAC 2011

MD Conference Express ICAAC 2011
Contents
Infectious Disease Genomics
Emerging Resistance Among Gram-Negative Pathogens
Procalcitonin-Guided Antibiotic Therapy In Patients with Lower Respiratory Tract Infections
Combination Therapy with Flucytosine Improves Survival in AIDS-Related Cryptococcal Meningitis
CXA-201 Effective Against Common ICU Pathogens
Tigecycline Plus Standard Therapy Is More Effective For Treating Infections in Febrile Neutropenic Cancer Patients
Interventions Aimed at Reducing MRSA BSIs Led to Decreased Rates of Nosocomial MSSA BSIs
Is the Effectiveness of aP Vaccine in Pre-Adolescents Insufficient?
TMC435 Effective in the Treatment of HCV Genotype 1 Infection
HIV
Vaccines
Antibiotic Resistance
Drug Discovery
The Conundrum of MDR TB and Combination Therapy
New Drugs to Treat MDR Pathogens
Immunizations in Reproductive Health
Why Can’t Microbes Just Get Along?
The Role of Adjunctive Steroids in the Treatment of Bacterial Meningitis
Human and Animal Viruses Share “One World” and Emerging Zoonotic Infections Continue to Threaten

MD Conference Express ICAAC 2011

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