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Antibiotics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Key Words Sterilization/disinfection/antisepsis Antibiotic Selective toxicity Bactericidal Bacteriostatic Minimal inhibitory concentration (MIC) Susceptibility  testing Penicillin binding proteins Penicillinase/beta lactamas Resistance
 
 
Selective Toxicity ,[object Object]
 
Improved Patient Outcomes Associated With Proper Hand Hygiene Semmelweis Chlorinated lime hand antisepsis
Antibiotics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
History ,[object Object],[object Object],[object Object],[object Object]
Neem Plant
Neem Plant ,[object Object]
Propolis
Propolis ,[object Object]
Ehrlich’s Magic Bullets
Gerhard Domagk - Prontosil
Fleming and Penicillin
Selman Waksman
Between 1962 and 2000, no major classes of antibiotics were introduced   Fischbach MA and Walsh CT  Science  2009
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
Azamulin
Daptomycin chemical structure . Steenbergen J N et al. J. Antimicrob. Chemother. 2005;55:283-288 JAC vol.55 no.3 © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Daptomycin mechanism of action . Steenbergen J N et al. J. Antimicrob. Chemother. 2005;55:283-288 JAC vol.55 no.3 © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Linezolid
 
Ideal Antimicrobial Attributes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
ANTIBIOTICS ,[object Object],[object Object],[object Object],[object Object]
Antibiotic/Antimicrobial ,[object Object],[object Object]
Microbial Sources of Antibiotics
Administration of Antibiotics
Spectrum of Activity
Determining Microbial Sensitivities ,[object Object],[object Object],[object Object],[object Object]
 
 
Drug Mechanisms of Action
[object Object],[object Object],[object Object],[object Object],[object Object],Antibacterial Antibiotics  Inhibitors of Cell Wall Synthesis
Prokaryotic Cell Walls
 
 
Cell wall synthesis ,[object Object],[object Object],[object Object],[object Object]
Antibiotics weaken the cell wall, and cause the cell to lyse .
Penicillin ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
- 4C – 28C  - 38C  water activity 0.98
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
 
 
 
Penicillins Figure 20.6
 
[object Object],[object Object],[object Object],[object Object],[object Object],Semisynthetic Penicillins
Penicillinase (   Lactamase)
[object Object],[object Object],Other Inhibitors of Cell Wall Synthesis Figure 20.9
Cephalosporin ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
The  different R groups allow for versatility  and improved effectiveness.
 
Other Inhibitors of Cell Wall Synthesis ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Other Inhibitors of Cell Wall Synthesis
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Inhibitors of Protein Synthesis
 
Aminoglycosides ,[object Object],[object Object],Streptomyces  synthesizes many different antibiotics such as aminoglycosides, tetracycline, chloramphenicol, and erythromycin.
 
  Sites of inhibition on the procaryotic ribosome
 
 
Tetracycline ,[object Object],[object Object],[object Object],[object Object]
 
Tetracyclines   (bacteriostatic) tetracycline , minocycline and doxycycline ,[object Object],[object Object],[object Object],[object Object]
 
 
Spectinomycin   (bacteriostatic) ,[object Object],[object Object],[object Object]
Erythromycin ,[object Object],[object Object],[object Object],[object Object]
 
 
Streptomycin  - treat Plague
Chloramphenicol ,[object Object],[object Object],[object Object]
Chloramphenicol
UDP-glucuronyl transferase
Aminoglycoside
[object Object],[object Object],[object Object],Injury to the Plasma Membrane
[object Object],[object Object],[object Object],Injury to the Plasma Membrane
 
 
 
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Inhibitors of Nucleic Acid Synthesis
 
 
 
Inhibition of Nucleic Acid Synthesis ,[object Object]
 
 
Antibacterials — Antimetabolites ,[object Object],[object Object],[object Object],[object Object]
Folic acid synthesis ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],Competitive Inhibitors Figure 5.7
Sulfonamides compete with PABA for the active site on the enzyme. The sulfonamide Sulfamethoxazole is commonly used in combination with trimethoprim
 
 
Necrotizing Fasciitis ,[object Object]
 
 
 
Summary of Targets
Antibiotic Resistance Figure 20.20
Antimicrobial Resistance ,[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],Mechanisms of Antibiotic Resistance
Antibiotic Selection for Resistant Bacteria
What Factors Promote Antimicrobial Resistance? ,[object Object],[object Object]
Inappropriate Antimicrobial Use ,[object Object],[object Object],[object Object],[object Object]
Inappropriate Antimicrobial Use ,[object Object],[object Object],[object Object],[object Object]
Antibiotics in Foods ,[object Object],[object Object]
Consequences of Antimicrobial Resistance ,[object Object],[object Object]
 
Multi-Drug Resistant TB
MRSA “mer-sah” ,[object Object],[object Object],[object Object]
Proposals to Combat Antimicrobial Resistance ,[object Object],[object Object],[object Object],[object Object]
Proposals to Combat Antimicrobial Resistance ,[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],The Future of Chemotherapeutic Agents
Side Effects
Resistance to Drugs ,[object Object],[object Object]
Mechanisms of Drug Resistance ,[object Object],[object Object],[object Object]
Mechanisms of Drug Resistance ,[object Object],[object Object]
Generations of Drugs ,[object Object],[object Object]
Limiting Drug Resistance ,[object Object],[object Object],[object Object],[object Object],[object Object]
Antibiotic Resistance ,[object Object],[object Object],[object Object]
Mechanisms of Resistance ,[object Object],[object Object],[object Object]
Drug Resistance ,[object Object],[object Object]
How does drug resistance develop? ,[object Object]
 
Resistance Factors – R Factors ,[object Object],[object Object]
Conjugation – plasmids and chromosomal elements, conjugative transposons plasmids ,[object Object],[object Object],[object Object]
Resistance Genes ,[object Object],[object Object]
Integrons ,[object Object],[object Object],[object Object]
Mechanism of Transfer ,[object Object],[object Object],[object Object]
 
Origin of Antibiotic Resistant Genes ,[object Object],[object Object]
Origin of resistance ,[object Object],[object Object]
Specific mechanisms of drug resistance ,[object Object]
Gene expression ,[object Object],[object Object],[object Object],[object Object]
Resistance ,[object Object]
Drug Inactivation Mechanisms ,[object Object]
Decreased Drug Permeability or Increased Drug Transport ,[object Object],[object Object],[object Object]
Resistance ,[object Object]
Multidrug Resistant (MDR) Pumps ,[object Object],[object Object],[object Object]
PUMPS ,[object Object]
Change of Drug Receptors ,[object Object],[object Object]
Changes in Metabolic Patterns ,[object Object]
Natural selection and drug resistance ,[object Object],[object Object]
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
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
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
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 .
 
Conjugative transposons ,[object Object],[object Object]
 
 

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Antibiotics ppt

Notas do Editor

  1. 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
  2. Daptomycin chemical structure.
  3. 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.
  4. 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
  5. 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
  6. 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
  7.   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. "MDR-GNB isolates" 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