Infectious Diseases I PDF

Infectious Diseases I iii. Adverse effects (a) Oseltamivir: Gastrointestinal (GI) (nausea and vomiting), central nervous system (CNS) (anxiety, headache, insomnia, etc.) (b) Zanamivir: Bronchospasm, cough (not recommended in patients with asthma or COPD) (c) Peramivir: Diarr...

Infectious Diseases I iii. Adverse effects (a) Oseltamivir: Gastrointestinal (GI) (nausea and vomiting), central nervous system (CNS) (anxiety, headache, insomnia, etc.) (b) Zanamivir: Bronchospasm, cough (not recommended in patients with asthma or COPD) (c) Peramivir: Diarrhea; and elevation of aspartate aminotransferase, alanine aminotransferase, creatinine phosphokinase, glucose iv. Dosage (a) Oseltamivir: 75 mg orally twice daily for 5 days; decrease dosage to 30 mg twice daily orally in patients with a creatinine clearance (CrCl) of 31–60 mL/minute/1.73 m2 and 30 mg once daily orally in patients with a CrCl of 11–30 mL/minute/1.73 m 2. (b) Zanamivir: Two inhalations (5 mg/inhalation) twice daily for 5 days (c) Peramivir: 600 mg intravenously once; decrease dose to 200 and 100 mg in patients with a CrCl less than 50 and 30 mL/minute/1.73 m2, respectively (d) Initiate within 48 hours of symptom onset. d. Endonuclease inhibitors i. Baloxavir ii. Inhibits viral endonuclease which is vital for initiating viral transcription; symptoms resolve 1-1.5 days sooner iii. Adverse effects: gastrointestinal, bronchitis, headache (all similar to placebo) iv. Dosage: 40 mg once (40-79 kg) or 80 mg once (greater than or equal to 80 kg) 5. Prevention a. Prophylaxis in the community i. Patients at very high risk of developing complications when influenza vaccination is contraindicated or for whom the vaccine is expected to have low effectiveness. Use for the duration of influenza activity. ii. Hematopoietic stem cell or lung transplant recipients. Use for the duration of influenza activity. iii. Patients at high risk of complications or people in close contact with these patients. Use short term and give vaccine. b. Prophylaxis for institutional outbreaks i. All exposed residents or patients in outbreak-affected units regardless of influenza vaccination history ii. Unvaccinated or recently vaccinated caregivers iii. Use prophylaxis for at least 14 days and continue for 7 days after the last identified case in the institution. c. Amantadine, rimantadine: Not recommended for prevention because of current universal resistance d. Use neuraminidase inhibitors only: Oseltamivir 75 mg/day orally H. Coronavirus disease (COVID-19) 1. Characteristics of COVID-19 infection a. Caused by the SARS-CoV-2 virus b. Pandemic with significant mortality c. Occurs throughout the year d. Transmitted by exposure to respiratory fluids e. Incubation period of 3–6 days e. Mortality greatest in adults older than 65 years and in those with chronic conditions ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-204 Infectious Diseases I 2. Therapy a. Symptomatic/not hospitalized/not receiving supplemental oxygen i. Ritonavir-boosted nirmatrelvir (Paxlovid) is preferred first-line therapy as of January 2023 (a) Dose: Nirmatrelvir 300 mg with ritonavir 100 mg orally twice daily for 5 days (b) Monitor patient closely for drug interactions ii. Remdesivir is preferred second-line therapy (see dose below) iii. Molnupiravir is an alternative therapy if preferred therapies are not available/appropriate b. Hospitalized/receiving supplemental oxygen i. Remdesivir (a) Dose: 200 mg once; then 100 mg daily for total of 5 days (b) Benefit greatest when given early in disease course (within 10 days of symptom onset) ii. Dexamethasone Dose: 6 mg orally or intravenously daily for 10 days; data also support doses of 20 mg daily for 5 days followed by 10 mg daily for 5 days and 12 mg daily for 10 days Do not continue after discharge unless patient is still receiving supplemental oxygen iii. In patients with rapidly increasing oxygen needs and systemic inflammation, consider adding an immunomodulatory drug: baricitinib, tocilizumab, sarilumab 3. Prevention a. Vaccination i. Pfizer-BioNTech vaccine – mRNA vaccine (a) Approved for age 12 years or older; Emergency Use Authorization (EUA) is 6 months–11 years (b) Monovalent vaccine (1) Dose for age 12 years and older: 0.3 mL (30 mcg) intramuscularly for 2 doses, 3–8 weeks apart; first booster at 5 months or more after the second dose; second booster at 4 months or more after the first booster in adults age 50 years and older (2) Dose for age 5–11 years: 0.2 mL (10 mcg) intramuscularly for 2 doses 3–8 weeks apart; first booster at 5 months or more after second dose (3) Dose for age 6 months to up to 5 years: 0.2 mL (3 mcg) intramuscularly for 2 doses 3–8 weeks apart; first booster at 5 months or more after second dose (4) Adverse reactions: Injection site pain/swelling/redness, fatigue, headache, muscle pain, chills, joint pain, fever, nausea, malaise, lymphadenopathy, hypersensitivity reactions, myocarditis/pericarditis (c) Bivalent vaccine (1) 0.3 mL (30 mcg) intramuscularly for 1 dose (2) Give at least 2 months after last dose of primary series/booster ii. Moderna vaccine – mRNA vaccine (a) Approved for age 18 years and older; EUA is 6 months–17 years (b) Monovalent vaccine (1) Dose for age 12 years and older: 0.5 mL (100 mcg) intramuscularly for 2 doses 4–8 weeks apart; first booster (50 mcg) at 5 months or more after second dose; second booster (50 mcg) at 4 months or more after first booster in those age 50 years and older (2) Dose for age 6–11 years: 0.5 mL (50 mcg) intramuscularly for 2 doses 4–8 weeks apart (3) Dose for age 6 months up to 6 years: 0.25 mL (25 mcg) intramuscularly for 2 doses 4–8 weeks apart (4) Adverse reactions: Injection site pain/swelling/redness, headache, fatigue, myalgia, nausea, fever, hypersensitivity reactions, cerebral venous sinus thrombosis, thrombocytopenia ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-205 Infectious Diseases I (c) Bivalent vaccine (1) 0.5 mL (50 mcg) intramuscularly for 1 dose (2) Give at least 2 months after last dose of primary series/booster iii. Janssen/J&J vaccine – adenovirus vector vaccine (a) EUA is age 18 years and older (b) Dose: 0.5 mL (5 × 1010 virus particles) intramuscularly for 1 dose; first booster (0.5 mL) at 2 months or more after primary dose (c) Adverse reactions: Injection site pain/swelling/redness, fatigue, headache, muscle pain, chills, joint pain, fever, nausea, malaise, and lymphadenopathy; hypersensitivity reactions; Bell’s palsy; myocarditis/pericarditis iv. Novavax vaccine, adjuvanted – recombinant protein subunit (a) EUA is age 18 years and older (b) Dose: 0.5 mL (5 mcg + 50 mcg adjuvant) intramuscularly for 1 dose; first booster (0.5 mL) 3 weeks after primary dose (c) Adverse reactions: Injection site pain/tenderness/redness/swelling/pruritis, fatigue/malaise, muscle pain, headache, joint pain, nausea/vomiting, fever, chills, hypersensitivity reactions, lymphadenopathy-related reactions, myocarditis/pericarditis Patient Case 3. S.C. is a 46-year-old woman who presents to the clinic with purulent nasal discharge, nasal and facial congestion, headaches, fever, and dental pain. Her symptoms began about 10 days ago, improved after about 4 days, and then worsened again a few days later. Which is the best empiric therapy for S.C.? A. Cefpodoxime proxetil 200 mg orally twice daily. B. Clindamycin 300 mg orally four times daily. C. Amoxicillin/clavulanate 875 mg/125 mg orally twice daily. D. No antibiotic therapy needed. I. Sinusitis 1. Definition and etiology a. Inflammation of the mucosal lining of the nasal passage and paranasal sinuses lasting up to 4 weeks b. Many different causes, including viruses, bacteria, and fungi c. Viruses account for more than 90% of cases, whereas bacteria account for less than 10%. 2. Diagnosis a. Presence of at least two major symptoms or one major and two or more minor symptoms (Table 7) Table 7. Symptoms Associated with Diagnosis of Sinusitis Major Symptoms Purulent anterior nasal discharge Purulent or discolored posterior nasal discharge Nasal congestion or obstruction Facial congestion or fullness Facial pain or pressure Hyposmia or anosmia Fever (for acute sinusitis only) Minor Symptoms Headache Ear pain, pressure, or fullness Halitosis Dental pain Cough Fever (for subacute or chronic sinusitis) Fatigue ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-206 Infectious Diseases I b. Viral or bacterial? (Table 8) Table 8. Differentiating Viral from Bacterial Sinusitis Characteristics Symptoms Peak symptoms Viral Nasal discharge, congestion, and scratchy throat Clear to purulent to clear; purulence not present until days 4–5 None (or early in course, resolving in 48 hr) Headache, facial pain, and myalgia (resolving in 48 hr) Days 3–6 Duration 5–10 days Nasal discharge Fever Other symptoms Bacterial Nasal discharge, congestion, and scratchy throat Persistent purulent discharge (> 10 days) or early and severe (first 3–4 days) or increased on days 5–6 after typical viral infection (“double-sickening”) High temperature (≥ 102.2°F [39°C]) and early (first 3–4 days) Headache, facial pain, myalgia, daytime cough Persistent > 10 days or early and severe (first 3–4 days) or improved symptoms that worsen on days 5–6 In general, > 10 days 3. Treatment a. Begin antibiotics as soon as bacterial sinusitis is diagnosed (see criteria in Table 8). b. First-line therapy i. Amoxicillin/clavulanate ii. High-dose amoxicillin/clavulanate (2 g /125 mg twice daily in adults or 90/6.435 mg/kg/day divided twice daily) in: (a) Geographic regions with high endemic rates (greater than 10%) of invasive penicillinnonsusceptible S. pneumoniae (b) Those with a severe infection (e.g., evidence of systemic toxicity with a temperature of 102.2°F (39°C) or higher and a threat of suppurative complications) (c) Attendance at day care (d) Age younger than 2 years or older than 65 years (e) Recent hospitalization (f) Antibiotic use within the past month (g) Those who are immunocompromised c. Second-line therapy i. Respiratory fluoroquinolone (including children with type I hypersensitivity to penicillin) – Because of serious adverse effects, avoid if there are other treatment options. ii. Doxycycline iii. Cefixime or cefpodoxime proxetil with clindamycin (for children with non–type I hypersensitivity to penicillin) iv. Intranasal saline irrigation as adjunctive therapy v. Intranasal corticosteroids as adjunctive therapy in patients with allergic rhinitis d. Therapy duration i. Adults: 5–7 days ii. Children: 10–14 days ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-207 Infectious Diseases I II. URINARY TRACT INFECTIONS A. Introduction 1. Most common bacterial infection in humans: 7 million office visits per year; 1 million hospitalizations 2. Many women (15%–20%) will have a urinary tract infection (UTI) during their lifetime 3. 1–50 years of age: UTIs occur predominantly in women; after 50: men are increasingly affected because of prostate problems B. Microbiology (Table 9) Table 9. Incidence of Urinary Tract Infections by Organism Community Acquired (%) Escherichia coli Staphylococcus saprophyticus Proteus mirabilis Klebsiella pneumoniae Enterococcus 73 13 5 4 2 Nosocomial (%) E. coli Fungal Pseudomonas aeruginosa Other gram-negative bacilli K. pneumoniae Staphylococcus aureus P. mirabilis Enterococcus 31 14 10 10 9 6 5 2 C. Predisposing Factors 1. Age 2. Female sex 3. Diabetes mellitus 4. Pregnancy 5. Immunosuppression 6. Urinary tract instrumentation 7. Urinary tract obstruction 8. Renal disease, renal transplantation 9. Neurologic dysfunction ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-208 Infectious Diseases I Patient Case 4. G.N. is a 62-year-old woman who presents to the emergency department with a 3-day history of urinary frequency and dysuria. During the past 24 hours, she has had nausea, vomiting, and flank pain. G.N. has a history of type 2 diabetes, which is poorly controlled, with some diabetes-related complications. G.N. also has hypertension and a history of several episodes of deep venous thrombosis. Her medications include glyburide 5 mg orally daily, enalapril 10 mg orally twice daily, warfarin 3 mg orally daily, and metoclopramide 10 mg orally four times daily. On physical examination, she is alert and oriented, with the following vital signs: temperature 102.8°F (39°C), heart rate 120 beats/minute, respiratory rate 16 breaths/minute, supine blood pressure 140/75 mm Hg, and standing blood pressure 110/60 mm Hg. Her laboratory values are within normal limits except for elevated international normalized ratio 2.7, BUN 26 mg/dL, SCr 1.88 mg/dL, and WBC 12,000 cells/mm3 (78 polymorphonuclear leukocytes, 7 band neutrophils, 10 lymphocytes, and 5 monocytes). Her urinalysis reveals turbidity, 2+ glucose, pH 7.0, protein 100 mg/dL, 50–100 WBCs, positive nitrites, 3–5 red blood cells, and many bacteria and positive for casts. Which is the best empiric therapy for G.N.? A. Trimethoprim/sulfamethoxazole double strength orally twice daily for 7 days. Monitor INR carefully. B. C  iprofloxacin 400 mg intravenously twice daily and then 500 mg orally twice daily for a total of 7 days. Monitor INR carefully. C. Gentamicin 140 mg intravenously every 24 hours for 3 days. D. Tigecycline 100 mg once, then 50 mg intravenously every 12 hours and then doxycycline 100 mg orally twice daily for a total of 10 days. D. Clinical Presentation 1. Lower UTI: Cystitis (older adults may have only nonspecific symptoms, such as mental status changes, abdominal pain, and decreased eating or drinking) a. Dysuria b. Frequent urination c. Urgency d. Occasionally, gross hematuria 2. Upper UTI: Pyelonephritis (older adults may have only nonspecific symptoms, such as mental status changes, abdominal pain, and decreased eating or drinking) a. Frequency, dysuria, hematuria b. Suprapubic pain c. Costovertebral angle tenderness; flank pain d. Fever, chills e. Elevated WBC f. Nausea, vomiting 3. Factors associated with or used to define complicated UTI (UTI involving a structural or functional abnormality) a. Male sex b. Hospital acquired c. Pregnancy d. Anatomic abnormality of the urinary tract e. Poorly controlled diabetes mellitus f. Recent antimicrobial use g. Indwelling urinary catheter h. Recent urinary tract instrumentation i. Immunosuppression ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-209 Infectious Diseases I 4. Recurrent cystitis a. Relapse: Infection with the same organism within 14 days of discontinuing antibiotics for the preceding UTI b. Reinfection: Infection with a completely different organism; most common cause of recurrent cystitis E. Diagnosis: Urinalysis (blood cultures will be positive in 20% of patients with upper UTIs) 1. Pyuria (WBC greater than 10 cells/mm3) 2. Bacteriuria (more than 102 colony-forming units per milliliter is diagnostic) in symptomatic patients or those with catheters 3. Red blood cells 4. Cloudiness 5. Nitrite positive (E. coli, Proteus, Klebsiella) 6. Leukocyte esterase positive 7. Casts (if pyelonephritis) 8. Note: patient must also have symptoms; diagnosis cannot be made on urinalysis results alone. F. Asymptomatic Bacteriuria 1. Asymptomatic bacteriuria should only be screened for and treated in pregnant women, patients undergoing endoscopic urologic procedures, and renal transplant recipients in the first 30 days after transplantation. a. Pregnant women should be treated for 4–7 days. b. Patients undergoing endoscopic urologic procedures should be treated with one or two doses of antibiotics. 2. Patients with functional and/or cognitive impairment should not be treated for asymptomatic bacteriuria solely on the basis of a history of falls or mental status changes/confusion. Patients must have local urinary symptoms or systemic signs of infection. G. Therapy 1. Uncomplicated cystitis a. Recommended therapy i. Trimethoprim/sulfamethoxazole 160 mg/800 mg twice daily for 3 days. Avoid if resistance prevalence is known to exceed 20% or if used for UTI in previous 3 months. ii. Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days (ineffective in patients with a CrCl less than 30 mL/minute/1.73 m2) iii. Fosfomycin tromethamine 3 g, one dose b. Alternatives i. Fluoroquinolones (not moxifloxacin) for 3 days – Because of serious adverse effects, avoid fluoroquinolones if there are other treatment options. ii. β-Lactams (amoxicillin-clavulanate, cefdinir, cefaclor, cephalexin, and cefpodoxime proxetil) for 5–7 days 2. Uncomplicated pyelonephritis a. Outpatient therapy (if patient is not immunocompromised or does not have nausea and vomiting) i. Trimethoprim/sulfamethoxazole 160 mg/800 mg twice daily for 14 days ii. Levofloxacin 750 mg orally daily for 5 days or ciprofloxacin 500 mg orally twice daily for 7 days (not moxifloxacin) – Because of serious adverse effects, avoid fluoroquinolones if there are other treatment options. iii. β-Lactams (see above) for 10–14 days (less effective than first two options) b. Uropathogen resistance greater than 10%: Use initial dose of an intravenous, long-acting β-lactam (e.g., ceftriaxone) or once-daily aminoglycoside. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-210 Infectious Diseases I 3. Complicated UTIs a. Outpatient therapy i. Trimethoprim/sulfamethoxazole 160 mg/800 mg twice daily for 7-14 days ii. Levofloxacin 750mg oral daily for 5 days or ciprofloxacin 500mg oral twice daily for 7 days (not moxifloxacin) iii. β-Lactams (see above) for 7–14 days b. Inpatient therapy i. Fluoroquinolone ii. Aminoglycoside iii. Ceftriaxone (consider a β-lactam with antipseudomonal activity in patients recently hospitalized or with urinary catheters or living in nursing homes) iv. Therapy duration: 5–14 days (5 days with levofloxacin) 4. Pregnancy (pregnant women should be screened for bacteriuria and treated, even if asymptomatic) a. Antibiotic options i. Amoxicillin/clavulanate for 3-7 days ii. Nitrofurantoin (avoid in the first trimester and at term if other options available) for 5-7 days iii. Cephalexin or cefpodoxime proxetil for 3-7 days iv. Fosfomycin tromethamine single dose b. Antibiotics to avoid i. Fluoroquinolones ii. Tetracyclines iii. Aminoglycosides iv. Trimethoprim/sulfamethoxazole (used frequently but avoidance recommended, especially during the late third trimester) 5. Recurrent cystitis a. Relapse i. Assess for pharmacologic reason for treatment failure. ii. Longer treatment (for 2–6 weeks, depending on length of initial course) b. Reinfection (reassess need for continuous prophylactic antibiotics every 6–12 months) i. If patient has two or fewer UTIs in 1 year, use patient-initiated therapy for symptomatic episodes (3-day treatment regimens). ii. If patient has three or more UTIs in 1 year and they are temporally related to sexual activity, use postintercourse prophylaxis with trimethoprim/sulfamethoxazole single strength, cephalexin 250 mg, or nitrofurantoin 50–100 mg and counsel on voiding after intercourse. iii. If patient has three or more UTIs in 1 year that are not related to sexual activity, use daily or three times per week prophylaxis with trimethoprim 100 mg, trimethoprim/sulfamethoxazole single strength, cephalexin 250 mg, or nitrofurantoin 50–100 mg. 6. Catheter-related UTIs a. Short-term indwelling catheters i. Risk of bacteriuria is 5% for each day of catheterization. ii. By 30 days, 75%–95% of patients with an indwelling catheter will have bacteriuria. iii. Preventive antimicrobial therapy is not recommended; it only increases the chance of selecting out resistant organisms. iv. Asymptomatic patients with bacteriuria should not be treated. v. Symptomatic patients with bacteriuria should be treated with 7 days of antibiotics if symptoms resolve promptly and with 10–14 days of antibiotics if there is a delayed response (both durations whether or not catheter removed). Treat for 5 days with levofloxacin if the patient is not severely ill; treat for 3 days in women 65 years and younger who have their catheters removed and who do not have upper urinary tract symptoms. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-211 Infectious Diseases I vi. The most common organisms are E. coli (21.4%), Candida spp. (21.0%), Enterococcus spp. (14.9%), P. aeruginosa (10.0%), K. pneumoniae (7.7%), and Enterobacter spp. (4.1%). b. Long-term indwelling catheters i. Almost all patients will be bacteriuric with two to five organisms. ii. Asymptomatic patients should not be treated. Catheters do not need to be replaced. iii. Symptomatic patients should be treated for a short period (7 days) to prevent resistance, and catheter replacement may be indicated. 7. Prostatitis a. Acute bacterial prostatitis i. Primarily gram-negative organisms ii.  Therapy duration 2–4 weeks, can extend for an additional 2 weeks if patient remains symptomatic (a) Trimethoprim/sulfamethoxazole (b) Fluoroquinolones b. Chronic bacterial prostatitis i. Difficult to treat ii. Therapy duration 1–4 months (a) Trimethoprim/sulfamethoxazole (b) Fluoroquinolones 8. Epididymitis a. Sexually transmitted (most likely caused by C. trachomatis or N. gonorrhoeae) i. Ceftriaxone 500 mg (1000 mg if weight greater than 150 kg) intramuscularly once plus doxycycline 100 mg twice daily ii. Use levofloxacin 500 mg daily instead of doxycycline in men who practice insertive anal sex. iii. Duration: 10 days b. Non-sexually transmitted (most likely caused by enteric gram-negative organisms): i. Men with bladder outlet obstruction (benign prostatic hyperplasia) or who have undergone prostate biopsy, vasectomy, or other urinary tract instrumentation procedures ii. Levofloxacin 500 mg daily iii. Duration: 10 days III. SKIN AND SKIN STRUCTURE INFECTIONS A. Cellulitis 1. Description a. Acute spreading skin infection that involves primarily the deep dermis and subcutaneous fat b. Nonelevated, poorly defined margins c. Warmth, pain, erythema and edema, and tender lymphadenopathy d. Malaise, fever, and chills e. Usually, patient has had previous minor trauma, abrasions, ulcers, or surgery (could be tinea infections, psoriasis, or eczema). f. Often, patients have impaired lymphatic drainage. 2.  Microorganism: Usually Streptococcus pyogenes and occasionally S. aureus (rarely other organisms); blood cultures are rarely positive and not routinely recommended unless severe systemic symptoms are present or the patient is immunosuppressed 3. Treatment: 5–10 days (may extend therapy if infection has not improved) a. Penicillin G if definitively streptococcal b. First-generation cephalosporin (cefazolin, cephalexin) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-212 Infectious Diseases I c. Ceftriaxone d. Clindamycin e. Treat empirically for MRSA if associated with penetrating trauma, injection drug use, purulent drainage, nasal colonization with MRSA, concurrent evidence of MRSA infection elsewhere or systemic inflammatory response syndrome (SIRS) criteria (severe nonpurulent). i. Outpatient: Clindamycin, trimethoprim/sulfamethoxazole (add β-lactam for Streptococcus), doxycycline (add β-lactam for Streptococcus) ii. Inpatient: Vancomycin, linezolid, daptomycin, or telavancin B. Erysipelas 1. Description a. Acute spreading skin infection that involves primarily the superficial dermis b. Spreads rapidly through the lymphatic system in the skin (patients may have impaired lymphatic drainage) c. Usually occurs in infants and older adults d. Usually occurs on the legs and feet (facial erysipelas can occur, but this is less common) e. Warmth, erythema, and pain f. Edge of infection is elevated and sharply demarcated from the surrounding tissue. g. Systemic signs of infection are common, but blood cultures are positive only 5% of the time. 2. Microorganism: Group A Streptococcus (S. pyogenes), but occasionally groups G, C, and B are seen 3. Treatment: 5 days (may extend therapy if infection has not improved) a. Penicillin G b. Cefazolin c. Clindamycin C. Necrotizing Fasciitis 1. Description a. Acute, necrotizing cellulitis that involves the subcutaneous fat and superficial fascia b. Infection extensively alters surrounding tissue, leading to cutaneous anesthesia or gangrene. c. Very painful (pain out of proportion to appearance) d. Streptococcal infection: Either spontaneous or attributable to varicella, minor trauma (cuts, burns, and splinters), or surgical procedures e. Mixed infection: generally secondary to perianal abscess, abdominal surgery, trauma, decubitus ulcers, or injection sites in persons who inject drugs f. Significant systemic symptoms, including shock and organ failure 2. Microorganisms a. Mixed infection with facultative and anaerobic bacteria (Type 1) b. S. pyogenes (Type 2) 3. Treatment a. Surgical debridement: Most important therapy and often repeated debridement is necessary b. Antibiotics are not curative; given in addition to surgery (if used early, may be effective alone) c. Empiric therapy: Vancomycin or linezolid plus piperacillin/tazobactam or a carbapenem or ceftriaxone with metronidazole d. If group A streptococci, S. aureus, or Clostridium spp. suspected, clindamycin should be included in the empiric regimen to suppress toxin and cytokine production e. Streptococcal necrotizing fasciitis: High-dose intravenous penicillin plus clindamycin ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-213 Infectious Diseases I Patient Case 5. G.N. returns to the clinic in 6 months with no urinary symptoms, but her chief concern is now an ulcer on her right foot. She recently returned from a vacation in Florida and thinks she might have stepped on something while walking barefoot on the beach. Her foot is not sore but is red and swollen around the deep ulcer. Her medications are the same as in Patient Case 4. Vital signs are stable, and there is nothing significant on physical examination except for the right foot ulcer. Laboratory values are within normal limits (SCr 0.86 mg/dL). Which is the best empiric therapy for G.N.? A. Nafcillin 2 g intravenously every 6 hours for 6–12 weeks. B. T  obramycin 120 mg intravenously every 12 hours plus levofloxacin 750 mg intravenously every 24 hours for 1–2 weeks. C. Ampicillin/sulbactam 3 g intravenously every 6 hours for 2–3 weeks. D. Below-the-knee amputation followed by ceftriaxone 1 g intravenously every 24 hours for 1 week. IV. DIABETIC FOOT INFECTIONS A. Epidemiology 1. 25% of people with diabetes develop foot infections. 2. 1 in 15 needs amputation. B. Etiology 1. Neuropathy: Motor and autonomic a. Mechanical or thermal injuries lead to ulcerations without patient knowledge. b. Gait disturbances and foot deformities; maldistribution of weight on the foot c. Diminished sweating, causing dry, cracked skin 2. Vasculopathy: Decreased lower limb perfusion 3. Immunologic defects: Cellular and humoral C. Causative Organisms: In general, polymicrobial (average, 2.1–5.8 microorganisms) 1. S. aureus 2. Group A and B Streptococcus 3. Enterococcus 4. Proteus 5. E. coli 6. Klebsiella 7. Enterobacter 8. P. aeruginosa 9. Bacteroides fragilis 10. Peptostreptococcus D. Therapy 1. Preventive therapy a. Examine feet daily for calluses, blisters, trauma, and so forth. b. Wear properly fitting shoes. c. Do not walk barefoot. d. Keep feet clean and dry. e. Have toenails cut properly. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-214 Infectious Diseases I 2. Antimicrobial therapy a. Mild infections (and no antibiotics in the past month), defined as local infection involving only the skin and the subcutaneous tissue, with no SIRS criteria and erythema of 2 cm or less i. No MRSA risk factors: Dicloxacillin, nafcillin, cephalexin, cefazolin, levofloxacin, or clindamycin ii. MRSA risk factors (see below): Doxycycline or trimethoprim/sulfamethoxazole b. Moderate to severe infections, defined as local infection with erythema greater than 2 cm, or involving structures deeper than skin and subcutaneous tissues without (moderate) or with (severe) 2 or more SIRS criteria i. Ampicillin/sulbactam ii. Ertapenem iii. Cefoxitin iv. Moxifloxacin alone or ciprofloxacin/levofloxacin plus clindamycin v. Tigecycline vi.  If risk of P. aeruginosa (uncommon in diabetic foot infections and often a nonpathogenic colonizer), use piperacillin/tazobactam, ceftazidime, cefepime, meropenem, or imipenem. Risk factors for Pseudomonas include high local prevalence of Pseudomonas infection, warm climate, frequent exposure of the foot to water, a severe infection, and failure of previous therapy with nonpseudomonal antibiotics. vii. If risk of MRSA, use vancomycin, linezolid, or daptomycin. Risk factors for MRSA include history of MRSA infection or colonization, high local prevalence of MRSA, or a severe infection. c. Treatment duration: 1–2 weeks for mild infections and 2–3 weeks for moderate to severe infections. Extended duration is needed for osteomyelitis. After amputation, treatment duration is 2–5 days if there is no remaining infected tissue or or bone, 1–3 weeks if residual infected tissue only, and 4–6 weeks if residual infected bone. E. Surgical Therapy 1. Drainage and debridement (appropriate wound care) are very important. 2. Amputation is often necessary; if infection is discovered early, can maintain structural integrity of the foot. Patient Case 6. W.A. is a 55-year-old man who is admitted with weight loss, malaise, and severe back pain and spasms that have progressed during the past 2 months. He has also experienced loss of sensation in his lower extremities. Four months before this admission, he had surgery for a fractured tibia, followed by an infection treated with unknown antibiotics. W.A. has hypertension and a history of diverticulitis. On physical examination, he is alert and oriented, with the following vital signs: temperature 99.4°F (37.4°C), heart rate 88 beats/minute, respiratory rate 14 breaths/minute, and blood pressure 130/85 mm Hg. His laboratory values are within normal limits, except for WBC 14,300 cells/mm3, erythrocyte sedimentation rate 89 mm/hour, and C-reactive protein 12 mg/dL. Magnetic resonance imaging reveals bony destruction of lumbar vertebrae 1 and 2, which is confirmed by a bone scan. A computed tomography–guided bone biopsy reveals gram-positive cocci in clusters. Which is the best therapy for W.A.? A. Vancomycin 15 mg/kg intravenously every 12 hours for 6 weeks. B. Nafcillin 2 g intravenously every 6 hours for 2 weeks. C. Levofloxacin 750 mg orally every 24 hours for 6 weeks. D. Ampicillin/sulbactam 3 g intravenously every 6 hours for 2 weeks. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-215