19. Between 1962 and 2000, no major classes of antibiotics were introduced Fischbach MA and Walsh CT Science 2009
20. A Changing Landscape for Numbers of Approved Antibacterial Agents Bars represent number of new antimicrobial agents approved by the FDA during the period listed. 1983-87 1988-92 1993-97 1998-02 2003-05 2008 Infectious Diseases Society of America. Bad Bugs, No Drugs . July 2004; Spellberg B et al. Clin Infect Dis . 2004;38:1279-1286; New antimicrobial agents. Antimicrob Agents Chemother . 2006;50:1912 Resistance 0 0 2 4 6 8 10 12 14 16 18 Number of agents approved
45. The R group is responsible for the activity of the drug, and cleavage of the beta-lactam ring will render the drug inactive. Chemical structure of penicillins
96. Sulfonamides compete with PABA for the active site on the enzyme. The sulfonamide Sulfamethoxazole is commonly used in combination with trimethoprim
150. Antimicrobial Resistance: Key Prevention Strategies Susceptible Pathogen Optimize Use Prevent Transmission Prevent Infection Effective Diagnosis and Treatment Antimicrobial-Resistant Pathogen Antimicrobial Resistance Antimicrobial Use Infection
151. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults 12 Contain your contagion 11 Isolate the pathogen 10 Stop treatment when cured 9 Know when to say “no” to vanco 8 Treat infection, not colonization 7 Treat infection, not contamination 6 Use local data 5 Practice antimicrobial control 4 Access the experts 3 Target the pathogen 2 Get the catheters out 1 Vaccinate Prevent Transmission Use Antimicrobials Wisely Diagnose and Treat Effectively Prevent Infection
152. Antimicrobial Resistance Among Pathogens Causing Hospital-Acquired Infections Methicillin (oxacillin)-resistant Staphylococcus aureus Vancomycin-resistant enterococci Non-Intensive Care Unit Patients Intensive Care Unit Patients Source: National Nosocomial Infections Surveillance (NNIS) System
153. Prevalence of Isolates of Multidrug-Resistant Gram Negative Rods Recovered Within The First 48 h After Admission to the Hospital Pop-Vicas and D'Agata CID 2005;40:1792-8 .
154.
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Editor's Notes
Ignaz Philipp Semmelweis (1818-1865), a Hungarian obstetrician, introduced antiseptic hand hygiene techniques Semmelweis noted that postpartum women examined by medical students who did not wash their hands after performing autopsies had high mortality rates He required students to clean their hands with chlorinated lime before examining patients Maternal mortality declined from 12% to less than 1% after this hand hygiene intervention was implemented
Daptomycin chemical structure.
Daptomycin mechanism of action. Hypothetical steps: step 1, daptomycin binds to the cytoplasmic membrane in a calcium-dependent manner; step 2, daptomycin oligomerizes, disrupting the membrane; step 3, the release of intracellular ions and rapid cell death.
Once a pathogen produces infection, antimicrobial treatment may be essential However, antimicrobial use promotes selection of antimicrobial-resistant strains of pathogens As the prevalence of resistant strains increases in a population, subsequent infections are increasingly likely to be caused by these resistant strains Fortunately, this cycle of emerging antimicrobial resistance/multidrug resistance can be interrupted Preventing infections in the first place will certainly reduce the need for antimicrobial exposure and the emergence and selection of resistant strains Effective diagnosis and treatment will benefit the patient and decrease the opportunity for development and selection of resistant microbes; this requires rapid accurate diagnosis, identification of the causative pathogen, and determination of its antimicrobial susceptibility Optimizing antimicrobial use is another key strategy; optimal use will ensure proper patient care and at the same time avoid overuse of broad-spectrum antimicrobials and unnecessary treatment Finally, preventing transmission of resistant organisms from one person to another is critical to successful prevention efforts
The “12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults” intervention program is the first 12-step program to be launched because hospital patients are at an especially high risk for serious antimicrobial-resistant infections Each year nearly 2 million patients in the United States get an infection in a hospital Of those patients, about 90,000 die as a result of their infection More than 70% of the bacteria that cause hospital-acquired infections are resistant to at least 1 of the drugs most commonly used to treat them Persons infected with antimicrobial-resistant organisms are more likely to have longer hospital stays and to require treatment with second- or third-choice drugs that may be less effective, more toxic, and/or more expensive
The proportion of pathogens causing hospital-acquired infections that are resistant to target antimicrobial drugs continues to increase at an alarming rate Currently, more than 50% of Staphylococcus aureus isolates causing infections in intensive care units are resistant to methicillin; more than 40% are resistant in other hospital units Vancomycin-resistant enterococci (VRE) emerged in the late 1980s and are now endemic in many hospitals In many hospitals, more than 25% of enterococcal infections are caused by vancomycin-resistant strains
Background. The prevalence of multidrug resistance (MDR) among gram-negative bacilli is rapidly increasing. Quantification of the prevalence and the common antimicrobial coresistance patterns of MDR gram-negative bacilli (MDR-GNB) isolates recovered from patients at hospital admission, as well as identification of patients with a high risk of harboring MDR-GNB, would have important implications for patient care. Methods. Over a 6-year period, patients who harbored MDR-GNB (i.e., patients who had MDR-GNB isolates recovered from clinical cultures within the first 48 h after hospital admission) were identified. &quot;MDR-GNB isolates&quot; were defined as Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, and Klebsiella species isolates with resistance to at least 3 antimicrobial groups. A case-control study was performed to determine the independent risk factors for harboring MDR-GNB at hospital admission. Results. Between 1998 and 2003, the prevalence of MDR-GNB isolates recovered from patients at hospital admission increased significantly for all isolate species ( P < .001), with the exception of P. aeruginosa ( P = .09). Of 464 MDR-GNB isolates, 12%, 35%, and 53% of isolates were coresistant to 5, 4, and 3 antimicrobial groups, respectively. Multivariable analysis identified age 65 years (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.1 7.4; P < .04), prior exposure to antibiotics for 14 days (OR, 8.7; 95% CI, 2.5 30; P < .001), and prior residence in a long-term care facility (OR, 3.5; 95% CI, 1.3 9.4; P < .01) as independent risk factors for harboring MDR-GNB at hospital admission. Conclusion. A substantial number of patients harbor MDR-GNB at hospital admission. Identification of common coresistance patterns among MDR-GNB isolates may assist in the selection of empirical antimicrobial therapy for patients with a high risk of harboring MDR-GNB
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