Antibiotic-Use-Misuse-and-Abuse

Antibiotic Use, Misuse, and Abuse Brian Levy, MD Current Antibiotic Trends • In the United States, we are NOT very good about treating patients with antibiotics, in both the inpatient and outpatient settings • Per the CDC, numerous studies have shown that 30-50% of antibiotics prescribed in hospitals are unnecessary or inappropriate • Efforts to improve antibiotics are necessary to improve patient outcomes while reducing overall healthcare costs Problems with Antibiotic Misuse • Global problem of antibiotic resistance which is a public health crisis • Clostridium difficile infections • Health care costs • Adverse reactions to antibiotics • Drug interactions with antibiotics Antibiotic Resistance Antibiotic Resistance • Antibiotic resistance occurs after the administration of antibiotics where millions of bacteria may undergo selective pressure and the bacteria can develop mutations as well as the acquisition of new genes on plasmids • Per the CDC, in the US, there are at least million people infected with antibiotic resistant bacteria and 23,000 will die as a result Antibiotic Resistance • Even if not fatal, these infections can significantly have effects on extended hospital stays and costs • Many medical advancements such as joint replacements, organ transplants, cancer therapy, and treatment of chronic diseases such as diabetes, asthma, cystic fibrosis, bronchiectasis, and rheumatoid arthritis depend on the ability to fight infections Antibiotic Resistance Antibiotic Introduced • 1928 PCN • 1950 tetracycline • 1953 erythromycin • 1960 methicillin • 1972 vancomycin • 1985 imipenem • 1996 levofloxacin • 2000 linezolid • 2010 ceftaroline Organism Resistance Identified • • • • • • • 1940 PCN R-staphylococcus 1959 tetracycline R-shigella 1962 MRSA 1965 PCN R-pneumococcus 1968 erythromcyin R strep 1988 VRE 1996 levofloxacin R pneumococcus • 2002 Vanc resistant staph Antibiotic Resistance Antibiotic Introduced Organism Resistance Identified • 2002 vancomycin R-staph • 2004 multi drug resistant acinetobacter and pseudomonas • 2009 ceftriaxone RNeisseria • 2011 ceftaroline R-Staph Unfortunately Doctors Are Largely to Blame What Can Doctors and Hospitals Do? • Is the antibiotic indicated at all? • Is the appropriate antibiotic being given? • Is the right amount of time given for the antibiotic as opposed to a more extensive duration? • Is the right dose of the antibiotic being given? C Diff Treatment • In general avoid antiperistaltic medications • Relapse may occur in up to 20-25% of patients • For the first relapse, treat with a 10 day course of vancomycin, followed by a week taper • For multiple recurrences, fecal microbia transplantation is done and has shown promise to be successful (J Hosp Med, 11: 56, 2016) • Prophylaxis with vancomycin to prevent recurrent C diff in patients receiving antibiotics who have had prior c diff showed decrease in recurrence (Clin Infect Dis 63: 651, 2016) Gram Negative Bacteremia Gram Negative Bacteremia • Gram negative bacteremia is a major cause of morbidity and mortality in hospitalized patients • vs 14 days of treatment? • In hospitalized patients with gram negative bacteremia who achieved clinical stability before day 7, an antibiotic course of days was non-inferior to 14 days The primary outcome was at 90 days mortality, relapse, complications, readmission, or extended hospitalization (Clinical Infect Dis, Dec 2018) Staph Aureus Bacteremia Staph Aureus Bacteremia • Sepsis and septic shock are common • Mortality rate of 10-20% • Most common sources of infection: IVDU, intravascular catheters, skin and soft tissue infections (abscesses), bone and joint infections (osteomyelitis), pneumonia, endocarditis • Source not found in about 25% of cases Staph Aureus Bacteremia • Staph aureus bacteremia has a high risk of invasive disease if not treated promptly (osteomyelitis, endocarditis, etc) • Obtaining an echocardiogram is recommended in staph aureus bacteremia to rule out endocarditis (JAMA 312: 1330, 2014) • Identify primary and secondary foci of infection to reduce the risk of treatment failure or relapse (remove indwelling IV catheters, drain abscesses, infected joints aspirated) Staph Aureus Bacteremia • Until culture susceptibility results available, Vancomycin should be used as empiric therapy (Clinical Infect Dis 61: 361, 2015) • Treatment regimens: MSSA – nafcillin / oxacillin or cefazolin, MRSA – Vancomycin or daptomycin (significantly more expensive, typically reserved for Vancomycin failure) • For MSSA, Vancomycin has been shown to be less effective with more persistent bacteremia and relapse than betalactam agents and should not be used for MSSA unless the patient has an anaphylactic allergy to beta-lactams (Medicine (Baltimore), 2003, 82 (5): 33) Staph Aureus Bacteremia • For MSSA, cefazolin was found to have comparable results to anti-staphylococcal penicillins (BMC Infect Dis, 2018, 18: 508) • Treatment failures were higher with ceftriaxone than with cefazolin (Open Forum Infect Dis, 2018, May 18, (5)) • Always obtain follow up cultures to document clearance Positive blood cultures after 3-4 days of appropriate antibiotics is strong predictor of complicated bacteremia (i.e endocarditis, osteomyelitis, persistent abscess) Staph Aureus Bacteremia • Persistent bacteremia suggests endovascular infection and poor source control A search for the source with drainage or surgical debridement should be attempted Staph Aureus Bacteremia • Duraton of treatment – typically week for uncomplicated bacteremia (Anti Microb Agents Chemother 57: 1150, 2013) or 4-6 weeks for complicated bacteremia • What is uncomplicated bacteremia? Resolution of fever by day of therapy, negative blood cultures by day of therapy, presence of easily removable focus of infection, no echocardiographic signs of endocarditis, no osteomyelitis, no hematogenous secondary focus of infection, no pre-existing valve abnormalities (i.e prosthetic valve, rheumatic valve disease, bicuspid aortic valve), no implanted prosthetic device (i.e prosthetic hip) Staph Aureus Bacteremia • What is complicated bacteremia? Doesn’t meet the above mentioned criteria for uncomplicated Treatment for 4-6 weeks recommended for endocarditis or metastatic infection Treatment for 6-8 weeks for osteomyelitis Staph Aureus Bacteremia • What about treatment failure? This occurs with relapse or prolonged bacteremia while on appropriate therapy It is more common with vancomycin, MRSA infection, endocarditis, undrained focus, and vancomycin with MIC = For strains with an MIC > 2, an alternative agent to vancomycin should be used (JAMA 312: 1152, 2014) Staph Aureus Bacteremia • Treatment failure options for MRSA include: daptomycin, ceftaroline (Antimicrob Agents Chemother, 2017: 51 (2)), telavancin (Infect Dis, 47: 379, 2015)