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10/1/24 Blood Stream Infections (BSI) : Focus on Gram Positive Infection NINO MARZELLA, BS, MS, PHARMD, BCPS ASSOCIATE PROFESSOR OF PHARMACY PRACTICE LIU PHARMACY A & M SCHWARTZ COLLEGE OF PHARMACY AND HEALTH SCIENCES...

10/1/24 Blood Stream Infections (BSI) : Focus on Gram Positive Infection NINO MARZELLA, BS, MS, PHARMD, BCPS ASSOCIATE PROFESSOR OF PHARMACY PRACTICE LIU PHARMACY A & M SCHWARTZ COLLEGE OF PHARMACY AND HEALTH SCIENCES, LONG ISLAND UNIVERSITY CLINICAL PHARMACY SPECIALIST NEW YORK HARBOR HEALTHCARE SYSTEM (BROOKLYN CAMPUS) 1 CONTACT INFORMATION DR. NINO MARZELLA E – MAILS: *[email protected]* [email protected] PHONE: *BROOKLYN VA – 718.836.6600 EXT. 8064* LONG ISLAND UNIVERSITY – 718.488.3441 2 1  10/1/24 REQUIRED READING DIPIRO: PHARMACOTHERAPY A PATHOPHYSIOLOGIC APPROACH 12 ED. CHAPTER 134: BACTEREMIA AND INFECTIVE ENDOCARDITIS (DANIEL B CHASTAIN) 2022 3 LEARNING OBJECTIVES DEFINE “BACTEREMIA” IDENTIFY THE ETIOLOGY OF BACTEREMIA EXPLAIN THE PATHOGENESIS FOR THE DEVELOPMENT OF BACTEREMIA IDENTIFY CLINICAL MANIFESTATIONS RESULTING FROM BACTEREMIA INCLUDING PHYSICAL FINDINGS, LABORATORY ABNORMALITIES, BLOOD CULTURES, AND OTHER DIAGNOSTIC FINDINGS DIFFERENTIATE BETWEEN THE VARIOUS TYPES OF BACTEREMIA IDENTIFY THE RISKS AND COMPLICATIONS THAT ARE ASSOCIATED WITH BACTEREMIA BASED ON YOUR PHARMACOLOGY, MEDICINAL CHEMISTRY, AND CLINICAL PRINCIPLES FOR ID: DESIGN A TREATMENT REGIMEN FOR A PATIENT WITH STAPHYLOCOCCUS AUREUS BACTEREMIA (SAB) 4 2  10/1/24 PRESENCE OF VIABLE BACTERIA IN THE CIRCULATING BLOOD “BACTEREMIA” “BACTER” REFERS TO BACTERIA AND THE SUFFIX OF “EMIA” REFERS TO A CONDITION OF THE BLOOD OFTEN REFERRED TO AS BLOODSTREAM INFECTION (BSI) 5 BACTEREMIA BLOODSTREAM INFECTION (BSI) MICROORGANISMS ARE CAPABLE FOR CAUSING INFECTION SYMPTOMATIC CASES REQUIRE HOSPITALIZATION ACUTELY ILL COMMUNITY ACQUIRED (CA) HOSPITAL ACQUIRED (HA)/NOSOCOMIAL HIGHEST RISK FOR THE DEVELOPMENT OF BACTEREMIA ELDERLY ICU RELATED INFECTIONS AN IMMUNOCOMPROMISED HOST 6 3  10/1/24 PATHOPHYSIOLOGY NOT COMPLETELY ELUCIDATED DEPENDENT ON HOST IMMUNE SYSTEM Cellular innate and adaptive immune responses are GENETIC OR CONGENITAL AND ACQUIRED responsible for initial clearance of bacteria DEFICIENCIES Liver and spleen filter active bacteria in the circulating blood CIRCULATORY SYSTEM Colonization and translocation at the primary source of location Transient or can become local infection migrate to other organs (metastatic infection) Rule of thumb: Bacterial clearance depends on the infecting microorganism (inoculum and virulence) and host Pulmonary immune status Systemic Lymphatic 7 RISK FACTORS GRAM POSITIVE Skin soft tissue infection (portals of entry)/wounds, presence of indwelling prosthetic devices GRAM NEGATIVE (catheters, orthopedic hardware and cardiac devices), IVDU, post GI, GU, respiratory tract surgery (hospitalized patients) translocation from GI, GU, and Enterococcus spp. – translocation wounds from GI, GU Untreated urinary tract infections Staphylococcus aureus is the most most commonly cause community- common gram-positive organism acquired bacteremia Escherichia coli is the most common cause of gram-negative associated bacteremia 8 4  10/1/24 CATHETERIZATION INDEWLLING DEVICES AND TUBES (CLABSI) SURGICAL GI/GU BACTEREMIA SKIN/ABSCESS BONE AND JOINT RESPIRATORY CNS 9 RISK FACTORS o ADVANCED AGE IMMUNOCOMPROMISED HOST o IVDU o CHRONIC HEMODIALYSIS o INDWELLING DEVICES o HIV INFECTION o DIABETES MELLITUS o MALIGNANCY o TRANSPLANT RECIPIENTS o SOLID ORGAN o STEM CELL o CHRONIC LIVER DISEASE /LIVER FAILURE o ASPLENIA o URINARY RETENTION o RECENT SURGERY OR PROCEDURES o TRAUMA o MEDICATIONS o TREATMENT WITH GLUCOCORTICOIDS o IMMUNOSUPRESSIVE AGENTS 10 5  10/1/24 TERMS TO CONSIDER MODS Septic Shock Sepsis “BACTEREMIA” SIRS “SEPSIS” 11 Review DEFINITIONS FYI BACTEREMIA: BACTERIA ARE PRESENT IN THE BLOODSTREAM ASYMPTOMATIC OR SYMPTOMATIC PROCESS PATHOGEN AND PATIENT FACTORS SIRS: SYSTEMIC INFLAMMATORY RESPONSE SYNDROME IS CAUSED BY YOUR BODY’S OVERWHELMING RESPONSE TO A STRESSOR (TEMPERATURE, HR, RR, AND WBCS) SEPSIS: BACTEREMIA OR ANOTHER INFECTION TRIGGERS A SERIOUS RESPONSE WITHIN THE BODY SYMPTOMS ARE PROGRESSIVE AND INDICATIVE OF AN ACUTE INFECTION PROCESS INTERNAL VITAL ORGANS BEGIN TO FAIL KIDNEYS, HEART, LUNGS AND LIVER SEPTIC SHOCK: SEPSIS THAT CAUSES DANGEROUSLY LOW BLOOD PRESSURE (LIFE THREATENING) INTERNAL ORGANS RECEIVE LIMITED BLOOD SUPPLY AND AS A RESULT BEGIN TO FAIL MODS: IS A SYNDROME ASSOCIATED WITH THE FAILURE OF ONE OR MORE ORGAN SYSTEMS 12 6  10/1/24 CLASSIFICATION OF BACTEREMIA Primary – Focal Intravascular Consider: Modes of Community onset Transmission Nosocomial Associated Emerging Resistance with numerous bacterial species Secondary – Metastatic Foci Extravascular 13 IDENTIFY SOURCE OF INFECTION ** REMEMBER DETERMINING THE PRIMARY SOURCE OF INFECTION REMAINS CRITICAL IN THE MANAGEMENT OF BACTEREMIA ** APPROACH TO THE PATIENT HISTORY EXPOSURE HISTORY SOCIAL HISTORY DIETARY HABITS ANIMAL EXPOSURE TRAVEL HISTORY PE VITAL SIGNS LYMPHATICS SKIN INSPECTION FOR SIGNS AND/OR SYMPTOMS OF FOCAL INFECTIONS MINOR INFECTIONS – LOCALIZED TREATED OR UNKNOWN CHRONIC INFECTIONS FOREIGN BODY DEVICES OR HARDWARE 14 7  10/1/24 CLINICAL PRESENTATION Asymptomatic Limited number of bacteria which are rapidly removed from the bloodstream by Persistent fever, tachypnea, tachycardia, the immune system rigors, malaise, altered sensorium, hypotension, and gastrointestinal symptoms transient bacteremia may result in fever (abdominal pain, nausea, vomiting, which is transient diarrhea) Daily activities or medical or surgical procedures (surgical/prophylaxis ABX) Serious infection sepsis or septic shock valvular heart abnormalities (ABG’S and MULTI-organ failure) ARDS Sustained bacteremia leads to metastatic and AKI focal infection and/or sepsis Symptomatic Sepsis leading to Septic Shock may Abscess formation common in develop quickly in patients with significant Staphylococcal bacteremia and persistent bacteremia resulting in higher mortality 15 COMPREHENSIVE DIAGNOSIS ASSESSMENT OF VITALS WBC W/DIFF. LACTATE PROCALCITONIN CRP AND ESR URINALYSIS AND URINE CULTURE CXR STOOL STUDIES LP CT IMAGING ECHOCARDIOGRAPHY 16 8  10/1/24 COMPREHENSIVE DIAGNOSIS BLOOD CULTURE 2 – 3 SETS TAKEN FROM SEPARATE VENIPUNCTURE AVOID CONTAMINATION WITH NORMAL SKIN FLORA BLOOD CULTURE SAMPLING VOLUME OF BLOOD ~ 20 ML HOWEVER 8-10ML NUMBER OF CULTURES ESSENTIAL TIMING OF CULTURES FOLLOW-UP BLOOD CULTURES OFTEN NECESSARY ADDITIONAL SPECIMENS CAN BE OBTAINED WHEN APPLICABLE 17 TIMING OF BLOOD CULTURE TRANSIENT INTERMITTENT BACTERIA PRESENT FOR PERIODS OF TIME FOLLOWED BY NONBACTEREMIC PERIODS MANIPULATION OF INFECTED TISSUE, INSTRUMENTATION OF CONTAMINATED MUCOSAL SURFACES OR BACTERIAL INFECTIONS CONTINUOUS PERSISTENT BACTEREMIA 18 9  10/1/24 TREATMENT 19 APPROACH TO TREATMENT CLINCIAL (PHYSICAL EXAM, DIAGNOSTIC AND ID CONSULTATION) INITIATE EMPIRIC ANTIMICROBIALS (INITIALLY) EARLY INITIATION WITHIN 1 HOUR EMPIRIC ANTIMICROBIAL THERAPY INTRAVENOUSLY ADMINISTERED BACTERICIDAL APPROPRIATE PK/PD PARAMETERS APPROPRIATE DOSING TARGET EXPECTED PATHOGEN AND INFECTION SITE LOCATION AT TIME OF INFECTION (COMMUNITY OR NOSOCOMIAL) SEVERITY (DEGREE OF ORGAN FAILURES) RECENT ANTIMICROBIAL THERAPY (PAST 3 MONTHS) OR RESISTANT PATHOGENS: MRSA, MDR – PSEUDOMONAS, AND VRE ALWAYS CONSIDER PATIENT FACTORS PRIOR TO SELECTION OF ANTIMICROBIAL THERAPY 20 10  10/1/24 APPROACH TO TREATMENT CONTINUATION OF THERAPY BASED ON CULTURE AND SUSCEPTIBILITY RESULTS STREAMLINING OR DE-ESCALATION WITH PROMPT DISCONTINUATION OF ANTIBIOTIC THERAPY WHEN APPROPRIATE COST MINIMIZATION, DECREASED RISK OF DRUG-RELATED ADVERSE EVENTS, REDUCTION IN THE LIKELIHOOD OF EMERGENCE OF RESISTANT PATHOGENS ORAL THERAPY CAN BE RECOMMENDED WHEN THE PATIENT IS AFEBRILE FOR AT LEAST 48 HOURS, ORAL AGENT MUST BE SUSCEPTIBLE, AND PATIENT MUST REMAIN CLINICALLY STABLE WITH CLOSE MONITOR AND FOLLOW-UP SURGICALLY DRAINING OF ABSCESSES AND REMOVAL OF INTERNAL DEVICES/LINES THAT ARE THE SUSPECTED SOURCE OF INFECTION 21 STAPHYLOCOCCUS AUREUS BACTEREMIA (SAB) BLOOD CULTURES POSITIVE FOR S. AUREUS REQUIRES PROMPT CLINICAL EVALUATION AND EMPIRIC ANTIMICROBIAL THERAPY MUST EVALUATE FOR THE PRESENCE OF INFECTIVE ENDOCATDITIS SCREENING ECHOCARDIOGRAPH (TTE OR TEE) ADDITIONAL IMAGING IF NECESSARY Staphylococcus au reus bacteremia CT OR PET cases/100,000 po accounts for 50 pulation based Mor tality rate ap incidence ASSESSMENT FOR: Uniform guidelin proximating 20-3 0% es in clinical prac METASTATIC FOCI tice not availabl e EARLY SOURCE CONTROL INCISION AND DRAINAGE AND/OR REMOVAL OF INFECTED DEVICE/HARDWARE 22 11  10/1/24 SAB GENERAL APPROACH EMPIRIC ANTIMICROBIAL THERAPY RULE: ACTIVITY AGAINST MRSA INITIALLY WITH VANCOMYCIN OR DAPTOMYCIN DE-ESCALATE ANTIMICROBIAL TO BETA-LACTAM IF ISOLATE IS MSSA REMEMBER FOLLOW-UP BLOOD CULTURES SHOULD BE OBTAINED EVERY 24 – 48 HOURS TO ASSURE BACTERIAL CLEARANCE 23 INOCULUM EFFECT (Cefazolin) OBSERVED MIC (monitor) PCN sensitive Diminished efficacy with Vancomycin in PCN (4 MU IV every 4 hours) susceptible isolates NOT allergic to PCN (test for allergy) Routine combination therapy for gram positive (ID consultation) No benefit in the improvement of clinical MSSA outcomes and duration of bacteremia ONLY associated with ADRs MSSE ONLY benefit with rifampin in patients with prosthetic or orthopedic hardware Nafcillin or Oxacillin Cefazolin (2 grams IV every (2 grams IV every 4 hours) 8 hours) OR Vancomycin 24 12  10/1/24 MRSA BACTEREMIA *** “MIC creep” 0.5 – 2.0 mg/L MRSA DOC = Vancomycin (AUC/MIC) 400-600 MG/H/L AUC guided preferred or trough guided monitoring 1. Modification of S.aureus cell wall Clinical & Laboratory Standards Institute (CLSI) MIC 2. MIC creep breakpoints (E-test) 3. Acquisition of vanA plasmids < 2 mcg/ml = S 4-8 mcg/ml = I Daptomycin (Alternative) > 16 mcg/ml = R (MIC > 1 mcg/mL) HIGHER DOSES may be necessary European Committee on Antimicrobial Susceptibility PERFORM DAPTOMYCIN SUSCEPTIBILITY Testing (EUCAST) “see saw effect” > 2 resistant 25 MRSA BACTEREMIA Tailor regimen to susceptible options if available CA-MRSA Bactrim, clindamycin, TCNs PVL toxin Telavancin Oritavancin, dalbavancin HA-MRSA Linezolid, tedizolid – STATIC (NOT first line) Ceftaroline* Ceftobiprole Diminished daptomycin susceptibility MUST have ID CONSULTATION (COMBINATION THERAPY MAY BE CONSIDERED) Quinupristin/dalfopristin ONLY bacteremia associated with intravascular line, DO NOT USE due to ampicillin- and vancomycin-resistant Enterococcus faecium Tigecycline FQs except delafloxacin ? PLUS rifampin 26 13  10/1/24 DURATION OF THERAPY OPTIMAL DURATION OF THERAPY FOR BACTEREMIA IS UNKNOWN 7 - 14 DAYS LIMITED EVIDENCE SUGGESTS THAT THERE IS NO SIGNIFICANT DIFFERENCE IN MORTALITY, CLINICAL AND MICROBIOLOGICAL CURE BETWEEN SHORTER OR LONGER DURATIONS OF THERAPY IN CRITICALLY ILL PATIENTS DURATION OF THERAPY UNCOMPLICATED BACTEREMIA EXCLUSION OF IE INFECTION/SECONDARY METASTATIC INFECTION, OR PROSTHESIS; NEGATIVE F/U B/C WITHIN 2-3 DAYS; DEFERVESCENCE WITHIN 72 HOURS OF EFFECTIVE THERAPY 14 DAYS OF THERAPY AFTER FIRST NEGATIVE BLOOD CULTURE IV TO PO WHEN CLINICALLY STABLE AND ORAL REGIMEN IS SUSCEPTIBLE COMPLICATED BACTEREMIA LONGER DURATION OF THERAPY REQUIRED 4-6 WEEKS AT A MINIMAL 27 HOSPITAL ACQUIRED INFECTIONS CENTRAL LINE ASSOCIATED BLOOD STREAM INFECTION (CLABSI) INTRAVENOUS CATHETERS IMPREGNATED LOCK THERAPY TOPICAL CERTAIN SITUATIONS SHORT TERM CATHETERS (IN PLACE 14 DAYS) SHOULD BE REMOVED IF THE PATIENT IS DEVELOPING SIGNS OR SYMPTOMS OF SEPSIS OR ENDOCARDITIS, OR IF BLOOD CULTURES REMAIN POSITIVE FOR MORE THAN 72 HOURS 28 14  10/1/24 TREATMENT FAILURE TIME FOR MRSA CLEARANCE 3 - 7 DAYS OF ACTIVE THERAPY (MEDIAN) TREATMENT FAILURE PATIENT NOT RESPONDING OR PROGRESSING ON ACTIVE THERAPY PERSISTENT BACTEREMIA RESULTS IN TREATMENT FAILURE BUG – DRUG MISMATCH ACQUIRED RESISTANCE DRUG/DOSE OPTIMIZATION PK/PD LEADS TO SERIOUS COMPLICATIONS AND DEATH 29 SUMMARY BACTEREMIA CAN OCCUR SPONTANEOUSLY AND OFTEN TRANSIENT INFECTIOUS DISEASE CONSULTATION SYMPTOMS ARE TYPICALLY MILD (FEVER) ISOLATION AND CONTACT PRECAUTION SUSTAINED BACTEREMIA MAY CAUSE METASTATIC FOCAL INFECTION OR COMPLICATED INFECTION PROCESS LEADING TO SEPSIS OR SEPTIC SHOCK BACTEREMIA IS MORE COMMON AFTER INVASIVE PROCEDURES, PARTICULARLY THOSE INVOLVING INDWELLING DEVICES OR MATERIAL IF BACTEREMIA IS SUSPECTED, INITIATE EMPIRIC ANTIBIOTICS WHEN THE PATHOGEN HAS BEEN IDENTIFIED DE-ESCALATE TO APPROPRIATE THERAPY BASED ON SUSCEPTIBILITY RESULTS SURGICAL INTERVENTION MAY BE REQUIRED 30 15  10/1/24 ADDITIONAL REFERENCES ** PRACTICE GUIDELINES ARE CURRENTLY BEING DEVELOPED** LIU C, BAYER A, COSGROVE SE, ET AL. "MANAGEMENT OF PATIENTS WITH INFECTIONS CAUSED BY METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS: CLINICAL PRACTICE GUIDELINES BY THE INFECTIOUS DISEASES SOCIETY OF AMERICA (IDSA)” CLINICAL INFECTIOUS DISEASES ; 52 (ISSUE 3) FEBRUARY 2011: PAGES E18 - E55. MERMEL LA, ALLON M, BOUZA E, ET AL. CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF INTRAVASCULAR CATHETER-RELATED INFECTION: UPDATE BY THE INFECTIOUS DISEASES SOCIETY OF AMERICA. CLIN INFECT DIS; 52 (ISSUE 9) MAY 2011: PAGES E162 - E193. 31 32 16