Slide 1Mechanism of actionSelect toxicityWhich to use?Did you know?Drug ResistanceThreat level URGENT (code level orange)Threat level SERIOUSThreat level ConcerningSlide 10Different ways to learn this materialGram positive – staph and strepGram positive cocciGram negativeGram negative organisms (don’t need to know the name)PseudomonasAnaerobesMycoplasmaSystemic fungiDestroy the wallCell Wall inhibitorsPCNPCNAmoxicillin/clavulanate (Augmentin)Pipercillin/tazobactam (Zosyn)CephalosporinsCeftriaxone (Rocephin)VancomycinIV VancomycinRed man syndromePO vancomycinDoxycyclineErythromycinClindamycinGentamycinMonitoring serum levelsANTI-INFECTIVE AGENTSNSG 325October 21, 2013Mechanism of action•Inhibit the bacterial cell wall synthesis or activate enzymes that destroy the cell wall•Increase bacterial cell membrane permeability•Inhibit protein synthesis•Causes lethal inhibition of protein synthesis•Inhibits bacterial synthesis or RNA & DNA•Disrupt specific biochemistry•Suppress viral replication•Do something to kill the bacteriaSelect toxicity•The ability to kill or damage the bacteria without damage to the host•Bacterial cells have many of the same structure as human cells. PCN has few SE because it targets structures that are absent in human cells. Therefore, PCN has high selective toxicity.Which to use?Antibiotics are chosen based on the type of bacteria that is causing infection. Gold standard: Culture and Sensitivity (right antibiotic for right drug) 3 days for it to come back so for the time being…Use broad spectrum antibioticsThen switch to focal therapyDid you know?•Over 2 million people acquire a serious infection with one or more resistant bacteria?•> 23,000 people die each year from antibiotic resistant infections.•250,000 people get hospital acquired C diff a year. 14,000 people die.•Estimated healthcare cost related to antibiotic resistant is $20 billion with an additional $35 billion for lost productivity. (2008 $ value)Drug Resistance•Innate or acquired? •Bacteria have changed in response to medications•CDC has categorizing drug resistant bacteria by threat level http://www.cdc.gov/drugresistance/threat-report-2013/•Report released 9/13Threat level URGENT (code level orange)•Clostridium difficile •Cabapenen-resistant Enterobacteriaceae (CRE)•Neisseria gonorrhoeaeThreat level SERIOUS•Multidrug resistant acinetobacter•Drug resistant campylobacter•Fluconazole resistant Candida•Extended spectrum b-lactamase producing enterocateriaceae (ESBLs)•VRE•Multidrug resistant Pseudomonas aeruginosa•Shigella•Salmonella•MRSA•TB – very problamatic in some populations (prison, poorer countries, areas with condensed living)Threat level Concerning•Vancomycin resistant Staphylococcus aureaus (VRSA)•Erythromycin-resistant Group A Streptococcus (flesh eating)•Clindamycin-resistant Group B StreptococcusDifferent ways to learn this material•Types of pathogens and antibiotics that are used to treat.•By the class of medication or how the medication worksWe will do both!Gram positive – staph and strep Nafcillin IV and Dicloxacillin PO provide excellent coverage against gram +First generation cephalosporins are effective against most skin and skin structure infections. Cefazolin (Ancef- cross sensitivity to penecillin) – given on almost every surgical patient prophylactically – three doses (reason: you cut into the skin)Staphylococcus StreptococcusGram positive cocci•Before PCN: gram positive cocci were responsible for the most infections.•They have developed a resistance to PCN.•Common site of infections for staph: Skin, wounds, surgical sites, indwelling catheters•Common site of infections for strep: pneumonia, meningitis, strep throatGram negativeThird generation cephalosporin's work well against gram – organisms. (four gen in total)Cephalosporins and penicillins may enhance the activity of aminoglycosides against gram neg bacteria. Such as Amp and Gent provides good coverage of gram +/- organismsTrimethoprim-sulfamethoxazole (Bactrim/Septra) work well against UTIAmoxocillin works well for Otitis Media and URIE. ColiH. influenzaeGram negative organisms (don’t need to know the name)Divide into 4 groups:•Enterics (in the gut) E Coli, Shigella, Salmonella, Klebsiella, Enterobacter Serratia, Proteus, plus others.•Haemophilus influenzae•Neisseria•Pseudomonas •Cause most nosocomial infections•Common site of infection: UTI, aspiration pneumonia, STDPseudomonas Gram-negative in environmentOverwhelming infection when host defenses are compromisedMedications: Ticarcillin or Ceftazidime cover most gram negatives. Imipenem and meropenem have good activity against PseudomonasRosefin works well withAnaerobesDoesn’t require oxygen for growth. (Usually found in GI tract in humans)•Metronidazole or clindamycin cover most anaerobic bacterial•Mouth anaerobes are adequately covered by PCNMycoplasmaLack a cell wall. Can cause pneumoniaErythromycin, Clarithromycin, Azithromycin(z-pack) are used to treat m pneumonia and other community acquired pneumoniaSystemic fungi•Fungi cause a wide variety of diseases in humans. Often encouraged by ABX use which causes death of normal flora which allows normal fungus to overgrow. •Examples: aspergillosis, Candidiasis, Coccidioidomycosis, Histoplasmosis•Most fungemia are treated with Amphotericin BDestroy the wallCell Wall inhibitors•Penicillin or β-lactam drugs•Developed in 1928•Bacteria changed and began to cleave the β-lactam ring therefore inactivating PCN •Second and third generations have resolved some of these issues.PCN•Blended with different salts. Potassium PCN G, Procaine penicillin G, Benzathine penicillin G•PCN G least toxic. Safe with the biggest problem being allergy•Between 0.4% and 7% of patients who receive PCN experience an allergic response. •Don’t need prior exposure because of antibiotic use in food supplyPCN•Can be administered PO, IM, IV•Dosage interval is usually 4-6 hours•Watch for signs of anaphylaxis•GI upset (most common)/pseudomembranous colitis can occur•May consider probiotics (yogurt) with ABX use•Continue taking medication until course is completeAmoxicillin/clavulanate (Augmentin)•Clavulanate is added to prevent cleaving of β-lactam chain. •PO dose 2-3 times a day•Decrease dose for ESRD•Treatment of otitis media, skin infections, sinusitis, URI, UTISE: diarrhea, anaphylaxis, serum