Bad Bugs in the Blood!

Transcription

1 Bad Bugs in the Blood! How to Work Up and Treat Bloodstream Infections Sharanjeet Thind M.D. Director of Inpatient Infectious Diseases, VA Medical Center Assistant Professor of Medicine, OUHSC, College of Medicine

2 Objectives Recognize the important pathogens that cause blood stream infections Identify the source of bacteremia by choosing appropriate laboratory and imaging tests Choose appropriate antimicrobial therapy to treat blood stream infections

3 Outline Bacteremias Definitions Sources of bacteremia Etiologic organisms Work Up of Bacteremias Identification of the source Utility of repeat blood cultures Treatment principals Antibiotic choice Duration of therapy Clinical Cases

4 Bacteremia Defined as the presence of viable microorganisms in the bloodstream May be transient, intermittent, continuous Transient: Lasts for a short amount of time, usually minutes or hours Following instrumentation of mucosal surfaces during dental procedures, cystoscopy, colonoscopy, after brushing your teeth Seifert et al. CID 2009; 28:S

5 Bacteremia Intermittent: Present in the blood for periods of time followed by nonbacteremic periods, due to a cycle of clearance and recurrence Most common pattern of bacteremia Undrained closed-space infections (abscesses) Focal infections such as pneumonia, osteomyelitis, meningitis Continuous: Endovascular infections; endocarditis, suppurative thrombophlebitis, infected aneurysm Seifert et al. CID 2009; 28:S

6 Epidemiology of Bloodstream Infections Bloodstream infection (BSI): presence of bacteria in association with infection High morbidity and mortality 10th leading cause of death in the United States patients develop BSIs every year in the US, most are acquired in hospitals May be primary or secondary; related to infections at other sites - urinary tract, skin and soft tissue, lung, catheters Mortality rate 16%-40% Importance of early antimicrobial therapy essential for survival 20% mortality with appropriate empiric therapy 34% inappropriate empiric therapy Leibovici L, et al. J Intern Med 1998;244: Wisplinghoff H et al. Clin Infect Dis 2004; 39:1093

7 Risk factors for BSI Hematopoietic stem cell, solid organ transplant Chronic liver disease Pulmonary disease Diabetes Hemodialysis HIV Steroids Elderly Greenberg BM et al. J Infect 2005; 50:288.

8 Source of Bacteremia Diekema et al. J Clin Microbiol Aug;41(8):

9 Other Sources of Bacteremia Joint infections Osteomyelitis Other device related infections Endocarditis Epidural abscess Primary bacteremia BMC Nephrology 2004, 5:18

10 Etiologic Organisms Prior to 1980s, Gram negative bacilli (GNB) were the predominant organisms associated with hospital-onset BSIs in the US E. coli, Klebsiella, Pseudomonas Since then Gram positive (GP) aerobes, candida spp. Coagulase negative staph (CoNS), Staph aureus, Enterococcus GNs still cause a high proportion of communityonset BSIs O'Grady NP et al. MMWR Recomm Rep 2002; 51:1 Gaynes R, Edwards JR. Clin Infect Dis 2005; 41:848.

11 Diekema, DJ et al. J Clin Microbiol Aug;41(8):

12 Etiologic Organisms Community Onset BSI GN bacteremias are more likely to be associated with community onset infections due to primary infections of the urinary tract, abdomen, respiratory tract Nosocomial BSI Most ~65% are caused by GPs (Staph aureus, CoNS, also Enterococci) 25% by GNs (E. coli, Klebsiella, Pseudomonas, Enterobacter, Acinetobacter, Serratia) 10% Candida spp. Associated with catheters Laupland KB et al. Clin Microbiol Rev Oct;27(4): Wisplinghoff et. Al. Clin Infect Dis, 2004, vol. 39 (pg )

13 Bloodstream Infections and Resistance Increasing number of resistant organism especially among nosocomial infections: Extended-spectrum β-lactamase (ESBL) producing GNs Carbapenem resistant Enterobacteriaceae (CRE) Proportion of S. aureus that is MRSA increased from ~ 22% in 1995 to 57% in 2001 in nosocomial setting, similar in community VRE in 60% of E. faecium

14 Summary of crude mortality by organism or group for communityonset and nosocomial bloodstream infection episodes Diekema, DJ et al. J Clin Microbiol Aug;41(8):

15 Gram Negative Bacteremias E. coli, Klebsiella, Proteus, Enterobacter, Pseudomonas Usually urinary source Gastrointestinal, hepatobiliary infections, aspiration pneumonia Catheter related bloodstream infections Diabetic foot infections Less likely than GPs to cause endovascular infections unless prosthetic material

16 ESBL E.coli 14% of HAI in OK ~ national resistance CRE 0.8% of HAI in OK, 3.5% nationally

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18 Gram Positive Bacteremias Staph aureus, coag negative Staph (CoNS), Enterococci, Streptococci (Group A Strep, Group B Strep, Strep pneumo) GPs tend to adhere to prosthetic devices, heart valves, form abscesses, biofilm Skin and soft tissue infections Strep, Staph, Enterococci Prosthetic device infections Staph (especially CoNS), Staph aureus, Enterococci Joint infections Staph, Strep Endocarditis Staph, Strep, Enterococci Pneumonia Strep pneumo CNS infections Strep pneumo

19 Gram Positive Bacteremias: Staph aureus MSSA or MRSA (about 50/50) Empirically start with vancomycin, daptomycin Can deescalate based on susceptibility data Repeat blood cultures to ensure clearance! Need to evaluate for endocarditis: Transthoracic echocardiogram (TTE) or transesophageal echocardiogram (TEE) Consult ID

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21 Gram Positive Bacteremias: CoNS Staph hominis, Staph capitis, Staph epidermidis, also Staph lugdunensis Normal part of skin flora Often a contaminant of blood cultures Increasingly a cause of infection Prosthetic devices, catheter related blood stream infections Repeat blood cultures to ensure clearance! May need to evaluate for endocarditis: TTE or TEE Large proportion are resistant to methicillin need to use vanco or dapto

22 Workup for Bacteremia Identify organism in blood cultures Repeat blood cultures before starting antibiotics (if possible) Identify source: may need imaging studies ex. abdominal CT for intraabdominal infection, TTE/TEE for endocarditis, CXR for pneumonia, lab studies ex. urinalysis and urine culture for UTI, sputum cultures for pneumonia, ESR/CRP for joint infections/osteomyelitis Duration of therapy is determined by source of infection and etiologic organism Call ID for help

23 Are repeat blood cultures necessary? Depends on the organism and the suspected source of bacteremia For Staphylococci, Streptococci, Enterococci YES! Gram negative bacteremia may clear more quickly, may not be necessary Patients with fever, leukocytosis, or other signs of ongoing infection Limited antimicrobial penetration at site (abscess, joint infection) Suspected endocarditis Presence of prosthetic vascular graft, cardiac device, catheters Resistant organisms Unknown source Canzoneri CN et al. Clin Infect Dis Nov 13;65(11):

24 Are repeat blood cultures necessary? Of 500 episodes of bacteremia, 383 (77%) that had at least 1 follow up blood culture (FUBC) Fever on the day FUBC) was associated with higher rates of positive FUBC for gram-positive cocci (GPC) but not GNB 17 FUBC for GNB and 5 FUBC for GPC needed to be drawn to yield 1 positive result FUBC added little value in the management of GNB bacteremia Indiscriminate use of repeat blood cultures could lead to increase in healthcare costs, longer hospital stays, unnecessary consultations, and inappropriate use of antibiotics Canzoneri CN et al. Clin Infect Dis Nov 13;65(11):

25 Is the organism a contaminant? Contamination can occur even when precise techniques for collection and processing are used More likely if: growth first occurs after 72 hours minority of blood cultures are positive ex. 1/4 bottles, 2/4 bottles repeat blood cultures before dose of antibiotic! Delayed growth can occur in patients with: Prior antimicrobial therapy Fastidious organisms: ex. Eikenella, Haemophilus spp., Kingella, Cardiobacterium ISDD Blood Collection Device Richter SS et al. J Clin Microbiol 2002; 40:2437.

26 Is the organism a contaminant? ALWAYS clinically important Strep pneumoniae Staph aureus Group A strep Hemophillus influenzae Enterobacteriaceae Pseudomonas aeruginosa Bacteroides spp. Candida spp. Possible contaminants Propionibacterium acnes Corynebacterium spp. Bacillus spp Coag neg staph Pien BC, et al. Am J Med 2010; 123:819.

27 Treatment Principals Source Control surgery, drainage procedures, removal of hardware, prosthesis, catheters Empiric antibiotics the earlier, the better Antibiotic choice - take into account patient's clinical syndrome, comorbidities, health care exposures, Gram stain/culture data, previous cultures, local resistance patterns Cover Pseudomonas? MRSA? Enterococci? Resistance organisms? Choice of antibiotic and duration of therapy is based upon: 1. Source (ensure penetration into the source) 2. Organisms ex. Staph aureus vs. GN (longer vs. shorter) 3. For endovascular infections, ensure antibiotic maintains good serum levels

28 Antibiotic Choice and Duration of Therapy 1. Source: ex. UTI, can use ceftriaxone, cefepime, piperacillin/tazobactam, cipro, start with IV therapy ex. pneumonia due to MRSA vanco or linezolid, NOT daptomycin 2. Organism: ex. BSI due to MRSA - at least 2-4 weeks of therapy vs. 1-2 weeks if E. coli or other GN 3. Ensure good serum levels for endovascular infections/primary bacteremias ex. endocarditis, use vanco or dapto for MRSA, nafcillin or cefazolin for MSSA, NOT linezolid

29 Duration of Therapy: Gram Negative Bacteremia No randomized controlled studies have evaluated the optimal duration of antibiotic therapy for GN bacteremia Duration should be determined by clinical response, source and severity/extent of infection Usually 7 to 14 days Antibiotics should be given parenterally, can be changed to oral agents with good bioavailability if afebrile for 48 hours Ceftriaxone, cefepime, pip/tazo, carbapenem, cipro/levo Chotiprasitsakul D et al. Clin Infect Dis Jan 6;66(2): Harvey TC et al. Crit Care. 2011; 15(6): R267.

30 Duration of Therapy GNs and GP Bacteremias Retrospective study of 700 patients with Enterobacteriaceae bacteremia Short courses (6-10 days) had similar clinical outcomes as prolonged courses (11-16 days) of antibiotic therapy, similar: mortality recurrent bacteremia Clostridium difficile trend towards lower risk for subsequent colonization or infection with MDR GNs Meta-analysis of patients with non Staph aureus bacteremia Intra-abdominal infection, CAP, pyelonephritis Shorter courses of therapy (5-7 days) vs. longer (7-21 days) course, no significant difference in: clinical outcomes microbiologic outcomes survival Chotiprasitsakul D et al. Clin Infect Dis Jan 6;66(2): Harvey TC et al. Crit Care. 2011; 15(6): R267.

31 Summary of Duration of Therapy Treatment for bacteremia is not always 14 days! Source of Infection Skin and soft tissue infection Urinary tract infection Catheter related BSI Pneumonia Abscess Endocarditis Osteomyelitis, septic arthritis, prosthetic joint infection Duration of Therapy 7-14 days 7 days 7-14 days 7-14 days 2-4 weeks, or longer 4-6 weeks 4-8 weeks

32 Case #1 62 M with Diabetes Mellitus (Hgb A1C of 10.7%), comes into the ER with fatigue, fever and decreased urine frequency WBC is , temp is F. UA shows many bacteria, >180 WBC The patient is given one dose of IV ceftriaxone and discharged with a 7 day course of sulfamethoxazole/trimethoprim Fever initially resolves but patient returns to the ED two days later, with dysuria, nausea and vomiting Temperature is 101 F, WBC is , creatinine is 1.6 (baseline 0.9) On exam, the patient has CVA tenderness, a renal US shows mild right sided hydronephrosis Urine culture and blood cultures from previous ED visit grew Klebsiella pneumoniae, S to ciprofloxacin, ceftriaxone, piperacillin/tazobactam R to sulfamethoxazole/trimethoprim

33 Case #1 What do you do next? Admit patient Do you need to repeat blood cx? Not necessary due to clear source of infection, GN bacteria but he is febrile and has a leukocytosis What antibiotic due you start? (K. pneumo, S to ciprofloxacin, ceftriaxone, pip/tazo R to smx/tmp) IV ceftriaxone or IV ciprofloxacin The next day, WBC improves to , creatinine is 1.2 and temperature is The patient still has some nausea and is not eating, IV ceftriaxone is continued. The following day (48 hours later), repeat blood cultures are still negative, creatinine has normalized, nausea and leukocytosis have resolved. What do you do next? PICC line and IV antibiotics, PO antibiotics? Convert to PO ciprofloxacin and discharge to complete 7 days

34 Case #2 A 48 F comes to the ED due to a 1-week history of nasal congestion, rhinorrhea, dry cough, fever, chills, and myalgia She was beginning to feel better until 48 hours ago when she developed a recurrence of fever and chills, a cough productive of blood-streaked yellow sputum, and right-sided pleuritic chest pain She has had no recent hospitalizations On PE, Temp is 39.0 C (102.2 F), BP is 100/50 mm Hg, HR is 110/min, and RR is 24/min, crackles are heard over the right lateral chest WBC is 20,000 a BUN/crt is 28/1.3 Modified from MKSAP 16

35 Case #2 Modified from MKSAP 16 Creative Commons CC0 1.0 Universal Public Domain Dedication.

36 Case #2 Which of the following is the most appropriate empiric treatment of this patient? A. Aztreonam B. Ceftriaxone and azithromycin C. Ceftriaxone and vancomycin D. Moxifloxacin

37 Case #2 The following day, blood cultures and sputum cultures are growing GPC in clusters The next day, the GPC is identified as Staphylococcus aureus R to oxacillin S to vancomycin, clindamycin, linezolid Repeat blood cx are negative, and the patient significantly improves with vancomycin TTE is ordered and is negative CT chest confirms pneumonia, no abscess is seen Ceftriaxone is discontinued

38 Case #2 Which antibiotic and for what duration is most appropriate for this patient? A. IV vancomycin for 6 weeks B. PO clindamycin for 4 weeks C. IV vancomycin for 2 weeks D. PO linezolid for 1 week

39 Case #3: A 54 M with hypertension, DM, ESRD on HD for 4 months via right chest tunneled dialysis catheter (TDC), is seen by his PCP when he developed a low grade fever after receiving HD. He recently received cipro for a UTI after a ED visit, completing a 7 day course 1 week prior to presentation On PE, vital signs are T 100.4, HR 98, BP 114/78, no erythema, warmth or tenderness around right internal jugular TDC What do you do next? Send the patient to the ED for blood cultures! WBC , 6 % bands, UA - 21 WBC Urine cultures and blood cultures are drawn and the patient is started on pip/tazo for a presumed UTI

40 Case #3 The following day, urine culture is negative, he is afebrile and the patient is discharged home to complete 5 days of amoxicillin/clavulanic acid Shortly after discharge the lab notifies the PCP about blood cultures that are growing

41 Case #3 What do you do next? Advise the patient to go to ED Do you need repeat blood cultures? Yes! 3-4 sets of blood cultures, at least 1 set peripherally and one through the TDC What antibiotic due you start? Vancomycin or daptomcyin GPC is identified as Staph. epidermidis S to vanco, smx/tmp, clindamycin, daptomycin Repeat blood cultures are growing GPC in both catheter and peripheral sets Is this a true bloodstream infection? What is the source? Other tests? TTE negative

42 Case #3 Now the challenging part What to do with the catheter? Retain + antibiotic lock therapy vs removal What is the duration of therapy? Vancomycin 14 days (5-7 days if catheter removed)

43 Take Home Points Bacteremias are associated with significant mortality Timely, appropriate antibiotics improve clinical outcomes and mortality Antibiotic choice should be based on suspected source, likely organisms Consider risk factors for MRSA, pseudomonas, resistant organisms Identify source with clinical presentation, imaging, lab tests Source control! Duration of therapy based on source, organism and the patient Call Infectious Diseases and Infection Control for help

44 Thank You! Questions?