Infectious Diseases I PDF

Infectious Diseases I 4. g. Add antifungal therapy if Candida spp. grown from intra-abdominal cultures h. Consider using antibiotics effective against Enterococcus (especially if patient has received cephalosporins, has valvular disease, is immunocompromised or post-operative) Therapy...

Infectious Diseases I 4. g. Add antifungal therapy if Candida spp. grown from intra-abdominal cultures h. Consider using antibiotics effective against Enterococcus (especially if patient has received cephalosporins, has valvular disease, is immunocompromised or post-operative) Therapy duration: 4 days following source control IX. CLOSTRIDIOIDES DIFFICILE INFECTION Patient Case 11. R.K. is a 72-year-old man who presents to the emergency department with a 2-day history of redness and swelling of his upper right extremity. He scraped his arm while clearing some brush in his yard. Although the scratch was initially healing, the area around the injury has become red and warm to the touch over the past few days, and the redness appears to be spreading. His medical history includes gastroesophageal reflux disease, hypertension, hyperlipidemia, and osteoarthritis. R.K. is taking pantoprazole 40 mg orally daily, lisinopril 20 mg orally daily, atorvastatin 40 mg orally daily, and acetaminophen 500 mg orally as needed. R.K. has no known drug allergies. R.K. is hospitalized and sent home after a few days with a prescription for oral clindamycin for his cellulitis. Two weeks after completing therapy for his cellulitis, R.K. has watery diarrhea. R.K. goes to the emergency department, and his C. difficile toxin is positive. His WBC is 24,500 cells/mm3, albumin is 2.8 g/dL, and SCr is 1.74 mg/dL (normally around 0.90 mg/dL). Which is the best therapeutic regimen for R.K.? A. Metronidazole 500 mg orally three times daily for 7 days. B. Vancomycin 125 mg orally four times daily for 10 days. C. Fidaxomicin 200 mg orally twice daily for 14 days. D. Rifaximin 400 mg orally twice daily for 7 days. A. Introduction 1. Clostridioides difficile is transmitted by the fecal-oral route. 2. Overgrowth in the GI tract occurs after antibiotic therapy. 3. Risk factors: Hospital stays, medical comorbidities (e.g., oncology, inflammatory bowel disease, chronic kidney disease, organ transplant), extremes of age, immunodeficiency states, use of broad-spectrum antibiotics, use of proton pump inhibitors 4. Production of endotoxins A and B causes pathogenesis. 5. Symptoms: Watery diarrhea, abdominal pain, leukocytosis, GI tract complications 6. Disease severity: a. Non-severe: Leukocytosis with WBC less than 15 x 103 cells/mm3 and SCr 1.5 mg/dL or less b. Severe: Leukocytosis with WBC 15 x 103 cells/mm3 or greater or SCr greater than 1.5 mg/dL c. Fulminant: Hypotension or shock or ileus or megacolon 7. BI/NAP1 strain produces more enterotoxin, produces binary toxin, has increased sporulation capacity, and is resistant to fluoroquinolones. Increased risk of metronidazole failure, morbidity, and mortality B. Therapy 1. Initial episode a. Nonsevere infection i. Vancomycin 125 mg orally four times a day for 10 days ii. Fidaxomicin 200 mg orally twice daily for 10 days. No difference in clinical cure rates compared with vancomycin but lowered incidence of recurrence. IDSA guidelines conditionally suggest using first line over vancomycin. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-228 Infectious Diseases I iii. Metronidazole may be used in low-risk (younger, minimal comorbidities) patients (500 mg orally three times daily for 10 days) b. Severe infection i. Vancomycin 125 mg orally four times a day for 10 days ii. Fidaxomicin 200 mg orally twice daily for 10 days. IDSA guidelines conditionally suggest using first line over vancomycin. c. Fulminant infection: Vancomycin 500 mg orally four times daily for 48–72 hours, followed by 125 mg orally four times daily for 10 days. Consider adding metronidazole 500 mg intravenously every 8 hours (especially in patients with ileus). In addition, in patients with ileus, add vancomycin per rectum 500 mg in 100 mL of saline as an enema four times daily. Can discontinue metronidazole and enemas if ileus resolves. 2. First recurrence a. Following metronidazole: Vancomycin 125 mg orally four times daily for 10 days or fidaxomicin 200 mg orally twice daily for 10 days b. Following vancomycin: i. Vancomycin prolonged taper and pulsed dosing: 125 mg orally four times daily for 10-14 days, then twice daily for a week, then daily for a week then every 2-3 days for 2-8 weeks ii. Fidaxomicin 200 mg orally two times daily for 10 days. IDSA guidelines conditionally suggest using fidaxomicin over vancomycin standard or pulsed dosing for first recurrences. c. Following fidaxomicin: Vancomycin prolonged taper and pulsed dosing. IDSA guidelines conditionally suggest using fidaxomicin for first recurrences over vancomycin standard or pulsed dosing (even with recurrences after fidaxomicin therapy). 3. Second and subsequent recurrences a. Fecal microbiota transplantation b. Fidaxomicin 200 mg orally twice daily for 10 days c. Vancomycin prolonged taper and pulsed dosing d. Vancomycin 125 mg orally four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 4. Recurrence prevention a. Oral vancomycin prophylaxis i. Alternative in patients when fidaxomicin not an option/unsuccessful (up to 8 weeks) ii. Option in high-risk (older than 65 or immunocompromised with C. difficile infection in past 3 months) patients needing systemic antibiotics (use during and for 5 days after antibiotic discontinuation) iii. Vancomycin 125 mg orally daily b. Bezlotoxumab i. Human monoclonal antibody that binds to C. difficile toxin B, preventing recurrent infections ii. Indicated in patients who are at high risk of recurrence (one or more prior episodes within the previous 6 months, older than 65, immunocompromised, or have clinically severe C. difficile infection at presentation) iii. Dose: 10 mg/kg intravenously as a single 60-minute infusion given during standard antibiotic therapy (does not replace standard antibiotic therapy) iv. Lower incidence of recurrent C. difficile infection in 12 weeks (17% vs. 27%) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-229 Infectious Diseases I Patient Case 12. You are a pharmacist who works closely with the surgery department to optimize therapy for patients undergoing surgical procedures at your institution. The surgeons provide you with principles of surgical prophylaxis that they believe are appropriate. Which is the best practice for optimizing surgical prophylaxis? A. Antibiotics should be redosed for extended surgical procedures; redose if the surgery lasts longer than 4 hours or involves considerable blood loss. B. All patients should be given antibiotics for 24 hours after the procedure; this will optimize prophylaxis. C. Preoperative antibiotics can be given up to 4 hours before the incision; this will make giving the antibiotics logistically easier. D. Vancomycin is the antibiotic of choice for surgical wound prophylaxis because of its long half-life and activity against MRSA. X. SURGICAL PROPHYLAXIS A. Introduction 1. Prophylaxis: Administering the putative agent before bacterial contamination occurs 2. Early therapy: Immediate or prompt institution of therapy as soon as the patient presents; usually, contamination or infection will have preceded the initiation of therapy (e.g., dirty wounds). B. Classification of Surgical Procedures (Table 17) Table 17. Classification of Surgical Procedures Surgical Procedure Clean: No entry is made in the respiratory, GI, or genitourinary tracts or in the oropharyngeal cavity In general, it is elective with no break in technique and no inflammation encountered Clean contaminated: Entry in the respiratory, GI, genitourinary, or biliary tracts or oropharyngeal cavity without unusual contamination Includes clean procedures with a minor break in technique Contaminated: Includes fresh traumatic wounds, gross spillage from the GI tract (without a mechanical bowel preparation), a major break in technique, or incisions encountering acute, nonpurulent inflammation Dirty: Includes procedures involving old traumatic wounds, perforated viscera, or clinically evident infection Infection Rate (%) 1–4 5–15 16–25 30–100 C. Risk Factors for Postoperative Wound Infections 1. Bacterial contamination a. Exogenous sources: Flaw in aseptic technique b. Endogenous sources i. Most important except in clean procedures ii. Patient flora causes infection 2. Host resistance a. Extremes of age b. Nutrition (i.e., malnourished patients) c. Obesity ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-230 Infectious Diseases I d. Diabetes mellitus (decreased wound healing and increased risk of infection) e. Immunocompromised f. Hypoxemia g. Remote infection h. Presence of foreign body (healthy person tolerates inoculum of 105, but in the presence of a foreign body, only 102 are needed) D. Indications for Surgical Prophylaxis 1. Common postoperative infection with low morbidity 2. Uncommon postoperative infection with significant morbidity and mortality E. Principles of Prophylaxis (Figure 1) 1. Timing: Antibiotics must be present in the tissues at the time of bacterial contamination (incision) and throughout the operative period; on-call dosing is not acceptable. a.  Administering antibiotics earlier than immediately preoperatively (within 60 minutes before incision or 60–120 minutes if using vancomycin or a fluoroquinolone) is unnecessary. b. Initiating antibiotics postoperatively is no more effective than not administering prophylaxis. c. Redose if the surgery lasts longer than 4 hours (or more than 2 half-lives of the antibiotic) or involves considerable blood loss. 6 Infection Rate (%) 5 4 3 2 1 0 Hours before incision Hours after incision < -2 -2 -1 1 2 3 4 5 6 7 8 9 10 >10 Figure 1. Relationship between timing of surgical prophylaxis and postoperative infection rate. Data from: Classen DC, Evans RS, Pestotnik SL, et al. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 1992;326:281-6. 2. Dosage a. Adequate dosing is necessary to prevent postoperative skin infections. Obese patients have a higher incidence of postoperative infections. b. Appropriate dosing i. Cefazolin: 2 g (3 g for patients weighing 120 kg or more) ii. Ceftriaxone, cefotetan, cefoxitin: 2 g iii. Clindamycin: 900 mg iv. Vancomycin: 15 mg/kg ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-231 Infectious Diseases I 3. 4. 5. 6. Duration a.  Most procedures, including GI, orthopedic, and gynecologic procedures, warrant antibiotics only as long as the patient is in the operating room; administration beyond surgical closure is not necessary. b. Cardiac procedures may warrant 24 hours of antibiotics after surgery. Spectrum a. Need only activity against skin flora unless the operation violates a hollow viscus mucosa b. GI, genitourinary, hepatobiliary, and some pulmonary operations warrant additional antibiotics. c. Colorectal surgery is one procedure in which broad-spectrum aerobic and anaerobic coverage is most effective. d. Try to avoid a drug that may be needed for therapy if infection occurs. Adverse reactions and bacterial resistance a. Antibiotic prophylaxis should not cause greater morbidity than the infection it prevents. b. Overuse may lead to resistance, which could prevent further use of the antibiotic for surgical prophylaxis or other infections (duration of administration is an important factor). Cost a. Prophylaxis can account for a substantial portion of the antibiotic budget. b. Must be weighed against the cost of treating one person with a postoperative infection F. Antibiotic Prophylaxis in Specific Surgical Procedures Note: For patients colonized with MRSA, a single preoperative dose of vancomycin can be added. 1. GI a. Gastric or duodenal i. Because of acidity, little normal flora ii. Rates of intragastric organisms and postoperative infections increase with increasing pH. iii. Indicated for morbid obesity, esophageal obstruction, decreased gastric acidity, or decreased GI motility iv. Recommendation: Cefazolin 2 g before induction b. Biliary i. Biliary tract normally has no organisms. ii. Indicated for high-risk patients. (Often, intraoperative cholangiography reveals unexpected common duct stones, so some studies recommend using antibiotics in all biliary surgery. In addition, studies have shown an increase in infection rates without risk factors.) (a) Acute cholecystitis (b) Obstructive jaundice (c) Common duct stones (d) Age older than 70 years iii. Recommendation: Cefazolin, cefoxitin, cefotetan, or ceftriaxone 2 g or ampicillin/sulbactam 3 g before induction c. Appendectomy i. Acutely inflamed or normal appendix: Less than 10% risk ii. Evidence of perforation: More than 50% risk (treatment necessary) iii. If perforated appendix, treat for 4 days. iv. Recommendation: Cefoxitin or cefotetan 2 g (or cefazolin plus metronidazole) before induction d. Colorectal i. A 30%–77% infection rate without antibiotics ii. One of the few surgical procedures in which coverage for aerobes and anaerobes has proved most effective ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-232 Infectious Diseases I iii. Preoperative antibiotics (a) Combined oral and parenteral regimens result in lower rates of surgical wound infections, anastomotic leaks, 30-day mortality, and postoperative ileus. (b) Oral regimens are inexpensive; however, some data suggest they are less effective when used alone (without parenteral agents), have greater toxicity, and may increase the risk of C. difficile infections. e. Recommendation i. Cefazolin or ceftriaxone 2 g plus metronidazole 500 mg (or cefoxitin or cefotetan 2 g or ampicillin/ sulbactam 3 g or ertapenem 1 g or gentamicin/tobramycin 5 mg/kg plus clindamycin 900 mg– metronidazole 500 mg) before induction ii. With or without neomycin 1 g orally and erythromycin 1 g orally at 19, 18, and 9 hours before surgery or neomycin 2 g orally and metronidazole 2 g orally at 13 and 9 hours before surgery iii. Mechanical bowel preparation is not recommended. 2. Obstetrics and gynecology a. Vaginal or abdominal hysterectomy i. Antibiotics are most effective in vaginal hysterectomies but generally are given for both procedures. ii. Recommendation: Cefazolin or cefoxitin or cefotetan 2 g (or ampicillin/sulbactam 3 g) before induction b. Cesarean section. Recommendation: Cefazolin 2 g after the cord is clamped 3. Cardiothoracic a. Cardiac surgery i. Antibiotics decrease the risk of mediastinitis. ii. Recommendation: Cefazolin or cefuroxime 2 g preinduction (plus intraoperative doses), if MRSA is probable or patient has been hospitalized, use vancomycin b. Pulmonary resection (i.e., lobectomy and pneumonectomy). Recommendation: Cefazolin 2 g before induction (or ampicillin/sulbactam 3 g or vancomycin 15 mg/kg) c. Vascular surgery i. High mortality with infected grafts ii. Recommendation: Cefazolin 2 g before induction and every 8 hours for three doses; if MRSA is probable, use vancomycin 4. Orthopedic a. Prophylaxis is indicated when surgery involves prosthetic materials (i.e., total hip or knee, nail, or plate). b. Recommendation: Cefazolin 2 g before induction (or vancomycin) 5. Head and neck a. Indicated for major surgical procedures when an incision is made through the oral or pharyngeal mucosa b.  Recommendation: Cefazolin or cefuroxime 2 g plus metronidazole 500 mg or ampicillin/sulbactam 3 g or clindamycin 900 mg before induction 6. Urologic a. In general, not recommended b. Indicated if patient has a positive urine culture before surgery (should treat and then operate) c. If therapy is unsuccessful, cover for the infecting organism and operate. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-233