Infectious Diseases I PDF

Infectious Diseases I V. OSTEOMYELITIS A. Introduction 1. Infection of the bone with subsequent bone destruction 2. About 20 cases per 100,000 people B. Characteristics (Table 10) Table 10. Characteristics of Osteomyelitis Hematogenous Spread Contiguous Spread Vascular Insufficiency Defini...

Infectious Diseases I V. OSTEOMYELITIS A. Introduction 1. Infection of the bone with subsequent bone destruction 2. About 20 cases per 100,000 people B. Characteristics (Table 10) Table 10. Characteristics of Osteomyelitis Hematogenous Spread Contiguous Spread Vascular Insufficiency Definition Spread of bacteria through the bloodstream from a distant site Spread of bacteria from an adjacent tissue infection or by direct inoculation Infection results from insufficient blood supply to fight the bacteria Patient population Children (< 16 yr): femur, tibia, humerus Adults (25–50 yr): femur, tibia, skull Adults (> 50 yr) Predisposing factors Bacteremia (e.g., IV catheters, IVDU, skin infections, URI) Open reduction of fractures Diabetes Sickle cell anemia Gunshot wound PVD Dental or sinus infections Post-CABG (sternum) Adult: vertebrae Soft tissue infections Common pathogens Usually monomicrobial Children: Staphylococcus aureus (60%–90%), Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Enterobacter, Escherichia coli (all < 5%) Usually mixed infection: S. aureus (60%), S. epidermidis, Streptococcus Gram-negative bacilli: P. aeruginosa (foot punctures), Proteus, Klebsiella, E. coli Adults: S. aureus and gram-negative bacilli Anaerobic (human bites, Sickle cell anemia: Salmonella (67%), decubitus ulcers) S. aureus, S. pneumoniae Usually polymicrobial: S. aureus, S. epidermidis, Streptococcus Gram-negative bacilli Anaerobic (Bacteroides fragilis group) Infected prosthesis: S. aureus, S. epidermidis IVDU: P. aeruginosa CABG = coronary artery bypass graft; IV = intravenous; IVDU = intravenous drug use; PVD = peripheral vascular disease; URI = upper respiratory infection; yr = year. C. Clinical Presentation 1. Signs and symptoms a. Fever and chills b. Localized pain, tenderness, and swelling c. Neurologic symptoms if spinal cord compression 2. Laboratory tests a. Elevated WBC b. Elevated erythrocyte sedimentation rate c. Elevated C-reactive protein 3. Diagnostic tests a. Radiographic tests: Positive results lag behind infectious process. b. Computed tomography and magnetic resonance imaging scans c. Radionuclide imaging: Positive as soon as 24–48 hours after infectious process begins. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-216 Infectious Diseases I D. Empiric Therapy 1. Pediatric (neonate therapy should be tailored to the patient) a. Cefazolin b. Nafcillin, oxacillin c. Clindamycin (use if prevalence of MRSA in community is 10% or more) d. Vancomycin (use if prevalence of MRSA and clindamycin-resistant S. aureus in community is 10% or more) 2. Adults a. Nafcillin, oxacillin, cefazolin, ceftriaxone, clindamycin, or vancomycin (alternatives linezolid or daptomycin) b. Choose additional antibiotics according to patient-specific characteristics. 3. Patients with sickle cell anemia: Ceftriaxone/cefotaxime or ciprofloxacin/levofloxacin (no studies assessing best empiric therapy). Patients are at risk of Salmonella. 4. Prosthetic joint infections a. Debridement and retention of prosthesis or one-stage exchange of prosthesis i. Staphylococcal: Pathogen-specific intravenous therapy plus rifampin 300–450 mg twice daily for 2–6 weeks, followed by rifampin plus ciprofloxacin or levofloxacin for 3 months (hip, elbow, shoulder, ankle prosthesis) or 6 months (knee prosthesis) ii. Nonstaphylococcal: Pathogen-specific intravenous (or highly bioavailable oral) therapy for 4–6 weeks, followed by indefinite oral suppression therapy b. Resection of prosthesis with or without planned reimplantation or amputation i. Pathogen-specific intravenous (or highly bioavailable oral) therapy for 4–6 weeks ii. Only 24–48 hours of antibiotic therapy after amputation if all infected tissue is removed E. Therapy Length 1. Acute osteomyelitis: 3–6 weeks 2. Chronic osteomyelitis: 6–8 weeks of parenteral therapy and 3–12 months of oral therapy F. Criteria for Effective Oral Therapy for Osteomyelitis 1. Highly bioavailable antibiotic is available. 2. Adherence 3. Identified organism that is highly susceptible to the oral antibiotic used 4. C-reactive protein less than 2.0 mg/dL 5. Adequate surgical debridement 6. Resolving clinical course VI. CENTRAL NERVOUS SYSTEM INFECTIONS A. Meningitis: Introduction 1. Incidence: About 8.6 cases per 100,000 people 2. Occurs more often in male than in female patients 3. More common in children B. Microbiology (Table 11) 1. Bacterial (septic meningitis) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-217 Infectious Diseases I Table 11. Bacterial Etiology of Meningitis, Based on Age Age < 1 mo (newborns) 1–23 mo 2–50 yr > 50 yr Most Likely Organisms Streptococcus agalactiae Listeria monocytogenes Streptococcus pneumoniae Neisseria meningitidis Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae Streptococcus agalactiae N. meningitidis S. pneumoniae S. pneumoniae N. meningitidis L. monocytogenes Less Common Organisms Escherichia coli, Klebsiella spp. Herpes simplex type 2 Viruses E. coli H. influenzae Viruses Streptococcus agalactiae, H. influenzae, aerobic gram-negative bacilli, viruses 2. Other causes (aseptic meningitis) a. Viral b. Fungal c. Parasitic d. Tubercular e. Syphilis f. Drugs (e.g., trimethoprim/sulfamethoxazole, ibuprofen) C. Predisposing Factors 1. Head trauma 2. Immunosuppression 3. CNS shunts 4. Cerebrospinal fluid (CSF) fistula or leak 5. Neurosurgical patients 6. Alcoholism 7. Local infections a. Sinusitis b. Otitis media c. Pharyngitis d. Bacterial pneumonia 8. Splenectomized patients 9. Sickle cell disease 10. Congenital defects D. Clinical Presentation 1. Symptoms a. Fever, chills b. Headache, backache, nuchal rigidity, mental status changes, photophobia c. Nausea, vomiting, anorexia, poor feeding habits (infants) d. Petechiae or purpura (Neisseria meningitidis meningitis) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-218 Infectious Diseases I 2. Physical signs a. Brudzinski sign b. Kernig sign c. Bulging fontanel E. Diagnosis 1. History and physical examination 2. Blood cultures 3. Lumbar puncture a. Elevated opening pressure b. Composition in bacterial meningitis (Table 12) Table 12. CSF Changes in Bacterial Meningitis Component Glucose Protein WBC Normal CSF 30–70 mg/dL (2/3 peripheral) < 50 mg/dL < 5 cells/mm3 pH Lactic acid 7.3 < 14 mg/dL Bacterial Meningitis < 50 mg/dL (≤ 0.4 CSF and blood) > 150 mg/dL > 1000–5000 cells/mm3 (predominantly neutrophils) 7.1 > 35 mg/dL Viral Meningitis Normal Normal to slightly elevated 5–300 cells/mm3 (predominantly lymphocytes) 7.3 < 14 mg/dL CSF = cerebrospinal fluid. c. CSF stains and studies i. Gram stain (microorganisms): Helps identify organism in 60%–90% of cases ii. Latex agglutination: High sensitivity, 50%–100%, for common organisms (a) Not recommended routinely (b) Most useful in patients pretreated with antibiotics with subsequent negative CSF Gram stains and cultures iii. Polymerase chain reactions (PCR): Detects most common causes of bacterial meningitis; high specificity and sensitivity iv. Acid-fast staining (tubercular meningitis) v. Cryptococcal antigen vi. Herpes simplex virus polymerase chain reaction 4. Laboratory findings a. Elevated WBC with a left shift b. CSF Gram stain c. CSF cultures (positive in 75%–80% of bacterial meningitis cases) d. Blood cultures (±) e. C-reactive protein concentrations: High negative predictive value ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-219 Infectious Diseases I Patient Case 7. D.M. is a 21-year-old university student who presents to the emergency department with the worst headache of his life. During the past few days, he has felt slightly ill but has been able to go to class regularly and eat and drink adequately. This morning, he awoke with a terrible headache and pain whenever he moved his neck. He has no significant medical history and takes no medications. He cannot remember the last time he received a vaccination. On physical examination, he is in extreme pain (10/10) with the following vital signs: temperature 102.4°F (39.1°C), heart rate 110 beats/minute, respiratory rate 18 breaths/minute, and blood pressure 130/75 mm Hg. His laboratory values are within normal limits, except for WBC 22,500 cells/mm3 (82 polymorphonuclear leukocytes, 11 band neutrophils, 5 lymphocytes, and 2 monocytes). A computed tomography scan of the head is normal, so a lumbar puncture is performed with the following results: glucose 44 mg/dL (peripheral, 110), protein 220 mg/dL, and WBC 800 cells/mm3 (85% neutrophils, 15% lymphocytes). Which is the best empiric therapy for D.M.? A. Penicillin G 4 million units intravenously every 4 hours. B. Ceftriaxone 2 g intravenously every 12 hours. C. Ceftriaxone 2 g intravenously every 12 hours plus dexamethasone 10 mg intravenously every 6 hours. D. Ceftriaxone 2 g intravenously every 12 hours plus vancomycin 1000 mg intravenously every 8 hours plus dexamethasone 10 mg intravenously every 6 hours. F. Empiric Therapy 1. Neonates (less than 1 month) a. Ampicillin plus aminoglycoside or b. Ampicillin plus cefotaxime 2. Infants (1–23 months): Ceftriaxone plus vancomycin* 3. Children and adults (2–50 years): Ceftriaxone plus vancomycin* 4. Older adults (50 years and older): Ceftriaxone plus vancomycin* plus ampicillin 5. Penetrating head trauma, neurosurgery, or CSF shunt: Vancomycin plus cefepime, ceftazidime, or meropenem *Vancomycin added for activity against highly drug resistant S. pneumoniae. G. Therapy for Common Pathogens 1. S. pneumoniae a. An MIC to penicillin of 0.1 mcg/mL or less i. Penicillin G 4 million units intravenously every 4 hours ii. Ampicillin 2 g intravenously every 4 hours iii. Alternative: Ceftriaxone 2 g intravenously every 12 hours or chloramphenicol 1–1.5 g intravenously every 6 hours b. An MIC to penicillin of 0.1–1.0 mcg/mL i. Ceftriaxone ii. Alternative: Cefepime 2 g intravenously every 8 hours or meropenem 2 g intravenously every 8 hours c. An MIC to penicillin of 2.0 mcg/mL or greater i. Vancomycin 15–20 mg/kg intravenously every 8–12 hours plus ceftriaxone ii. Alternative: Moxifloxacin 400 mg intravenously every 24 hours iii. If cephalosporin resistant: Vancomycin plus rifampin, vancomycin plus ceftriaxone or cefotaxime, rifampin plus ceftriaxone or cefotaxime, vancomycin plus moxifloxacin, linezolid ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-220 Infectious Diseases I 2. N. meningitidis a. An MIC to penicillin of less than 0.1 mcg/mL i. Penicillin G ii. Ampicillin iii. Alternative: Third-generation cephalosporin (cefotaxime or ceftriaxone) or chloramphenicol b. An MIC 0.1–1.0 mcg/mL i. Ceftriaxone ii. Alternative: Chloramphenicol, fluoroquinolone, or meropenem 3. H. influenzae a. β-Lactamase negative i. Ampicillin ii. Alternative: Third-generation cephalosporin (cefotaxime or ceftriaxone), cefepime, chloramphenicol, or fluoroquinolone b. β-Lactamase positive i. Third-generation cephalosporin (cefotaxime or ceftriaxone) ii. Alternative: Cefepime, chloramphenicol, or fluoroquinolone 4. Streptococcus agalactiae a. Penicillin G b. Ampicillin c. Alternative: Third-generation cephalosporin (cefotaxime or ceftriaxone) 5. Listeria monocytogenes a. Penicillin G b. Ampicillin c. Alternative: Trimethoprim/sulfamethoxazole 5 mg/kg intravenously every 6–12 hours or meropenem H. Therapy Length: Based on clinical experience, not on clinical data 1. N. meningitidis: 7 days 2. H. influenzae: 7 days 3. S. pneumoniae: 10–14 days 4. S. agalactiae: 14–21 days 5. Listeria monocytogenes: 21 days or more I. Adjunctive Corticosteroid Therapy 1. Risks and benefits a. Significantly less hearing loss and other neurologic sequelae in children receiving dexamethasone for H. influenzae meningitis b. Significantly improved outcomes, including decreased mortality, in adults receiving dexamethasone for S. pneumoniae meningitis c.  May decrease antibiotic penetration (decreased penetration of vancomycin in animals after dexamethasone) 2. Dosage and administration a. Give corticosteroids 10–20 minutes before or at same time as first dose of antibiotics. b. Dexamethasone 0.15 mg/kg or 10 mg every 6 hours for 2–4 days c. Use in children with H. influenzae meningitis or in adults with pneumococcal meningitis; however, may need to initiate before knowing specific causative bacteria. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-221 Infectious Diseases I Patient Case 8. D.M.’s CSF cultures grew N. meningitidis. Which is the best recommendation for meningitis prophylaxis? A. The health care providers in close contact with D.M. should receive rifampin 600 mg orally every 12 hours for four doses. B. Everyone in D.M.’s dormitory and in all of his classes should receive rifampin 600 mg orally every 24 hours for 4 days. C. Everyone in the emergency department at the time of D.M.’s presentation should receive the meningococcal conjugate vaccine. D. Everyone in the emergency department at the time of D.M.’s presentation should receive rifampin 600 mg orally every 12 hours for four doses. J. Chemoprophylaxis 1. N. meningitidis For close contacts (household or day care) and exposure to oral secretions of index case a. Rifampin i. Adults: 600 mg every 12 hours, four doses ii. Children: 10 mg/kg every 12 hours, four doses iii. Infants (younger than 1 month): 5 mg/kg every 12 hours, four doses b. Ciprofloxacin 500 mg orally, one dose (adults only) c. Ceftriaxone 125–250 mg intramuscularly, one dose 2. H. influenzae For all close contacts in households with unvaccinated or immunocompromised children a. Adults: Rifampin 600 mg daily for 4 days b. Children (1 month to 12 years): Rifampin 20 mg/kg/day for 4 days c. Infants younger than 1 month: Rifampin 10 mg/kg/day for 4 days K. Brain Abscess 1. Pathophysiology a. Direct extension or retrograde septic phlebitis from otitis media, mastoiditis, sinusitis, and facial cellulitis b. Hematogenous: Particularly lung abscess or infective endocarditis: 3%–20% have no detectable focus. 2. Signs and symptoms a. Expanding intracranial mass lesion: Focal neurologic deficits b. Headache c. Fever d. Seizures e. Mortality is about 50%. 3. Microbiology a. Usually polymicrobial b. Streptococcus spp. in 50%–60% c. Anaerobes in about 40% 4. Therapy a. Incision and drainage: By craniotomy or stereotaxic needle aspiration b. Suggested empiric regimens based on source of infection i. Otitis media or mastoiditis: Metronidazole plus ceftriaxone ii. Sinusitis: Metronidazole plus ceftriaxone ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-222 Infectious Diseases I c. iii. Dental sepsis: Penicillin plus metronidazole iv. Trauma or neurosurgery: Vancomycin plus ceftriaxone v. Lung abscess, empyema: Penicillin plus metronidazole plus sulfonamide vi. Unknown: Vancomycin plus metronidazole plus ceftriaxone Corticosteroids if elevated intracranial pressure Patient Case 9. T.S. is a 48-year-old man who presents to the emergency department with fever, chills, nausea and vomiting, anorexia, lymphangitis in his right hand, and lower back pain. He has no significant medical history except for kidney stones 4 years ago. He has no known drug allergies. He is homeless and was a person with substance use disorder (intravenous heroin) for the past year but quit 2 weeks ago. On physical examination, he is alert and oriented, with the following vital signs: temperature 100.8°F (38°C), heart rate 114 beats/minute, respiratory rate 12 breaths/minute, and blood pressure 127/78 mm Hg. He has a faint systolic ejection murmur, and his right hand is erythematous and swollen. His laboratory values are all within normal limits. He had an HIV test 1 year ago, which was negative. One blood culture was obtained in the emergency department that later grew MSSA. Two more cultures were obtained 24 hours after the first culture and are now both growing gram-positive cocci in clusters. A transesophageal echocardiogram reveals vegetation on the mitral valve. Which is the best therapeutic regimen for T.S.? A. Nafcillin therapy for 7–10 days. B. Nafcillin plus rifampin plus gentamicin therapy for 6 weeks or longer. C. Nafcillin plus gentamicin therapy for 2 weeks of both antibiotics. D. Nafcillin therapy for 6 weeks. VII. ENDOCARDITIS A. Introduction 1. Infection of the heart valves or other endocardial tissue 2. Platelet-fibrin complex becomes infected with microorganisms: Vegetation 3. Main risk factors include mitral valve prolapse, prosthetic valves, and persons who inject drugs. 4. Three or four cases per 100,000 people per year B. Presentation and Clinical Findings 1. Signs and symptoms a. Fever: Low grade and remittent b. Cutaneous manifestations (50% of patients): Petechiae (including conjunctival), Janeway lesions, splinter hemorrhage c. Cardiac murmur (90% of patients) d. Arthralgias, myalgias, low back pain, arthritis e. Fatigue, anorexia, weight loss, night sweats 2. Laboratory findings a. Anemia: Normochromic, normocytic b. Leukocytosis c. Elevated erythrocyte sedimentation rate and C-reactive protein d. Positive blood culture in 78%–95% of patients ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-223 Infectious Diseases I 3. Complications a. Congestive heart failure: 38%–60% of patients b. Emboli: 22%–43% of patients c. Mycotic aneurysm: 5%–10% of patients C. Microbiology (Table 13) 1. Three to five blood cultures of at least 10 mL each should be obtained during the first 24–48 hours. 2. Empiric therapy should be initiated only in acutely ill patients. In these patients, three blood samples should be obtained during a 15- to 20-minute period before antibiotics are initiated. Table 13. Incidence of Microorganisms in Endocarditis Organism Incidence (%) Streptococcus Staphylococcus aureus Enterococcus Coagulase-negative Staphylococcus Gram-negative bacilli Candida albicans 50 25 8 7 6 2 D. Treatment (Table 14) Table 14. Treatment Recommendation for Endocarditis Length of Therapy (wk) Native Prosthetic Valve Valve Organism Recommended Therapy Viridans streptococci (with PCN MIC ≤ 0.12 mg/L) PCN G 4 6 PCN G + gentamicina 2 6b Ceftriaxone 4 6 Ceftriaxone + gentamicin 2 6b Viridans streptococci (with PCN MIC > 0.12 mg/L) Staphylococcus, methicillin sensitive Vancomycin (only if unable to tolerate PCN or ceftriaxone) 4 6 PCN G + gentamicin 4c 6d Ceftriaxone (+ gentamicin if PCN MIC > 0.5 mg/L in native valves or MIC > 0.12 mg/L in prosthetic valves) 4 6d Vancomycin (only if unable to tolerate PCN or ceftriaxone) 4 6 Oxacillin or nafcillin Plus gentamicin and rifampin in prosthetic valves 6 ≥ 6c Cefazolin (only for nonanaphylactic penicillin allergy) Plus gentamicin and rifampin in prosthetic valves 6 ≥ 6c Vancomycin (only if severe PCN allergy) Plus gentamicin and rifampin in prosthetic valves 6 ≥ 6c ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-224 Infectious Diseases I Table 14. Treatment Recommendation for Endocarditis (Cont’d) Length of Therapy (wk) Native Prosthetic Valve Valve Organism Recommended Therapy Staphylococcus, methicillin resistant Vancomycin Plus rifampin and gentamicin in prosthetic valves 6 ≥ 6c Daptomycin (not for prosthetic valves) 6 — Enterococcus 4–6 6 Vancomycin + gentamicin (only if unable to tolerate a β-lactam) PCN G or ampicillin + gentamicin 6 6 Ampicillin + ceftriaxone 6 6 Enterococcus, PCN resistant Vancomycin + gentamicin 6 6 Enterococcus, PCN, aminoglycoside, and vancomycin resistant Linezolid >6 >6 Daptomycin >6 >6 HACEK group Ceftriaxone 4 6 Ampicillin/sulbactam 4 6 Fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) 4 6 Gentamicin should preferably be given as a single daily dose (3 mg/kg) for viridans streptococci endocarditis but may be given daily in three equally divided doses as an alternative. b Gentamicin can be added for 2 wk if CrCl is greater than 30 mL/minute/1.73 m 2. c Gentamicin for 2 wk. d Gentamicin for 6 wk. HACEK = Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella; MIC = minimum inhibitory concentration; PCN = penicillin. a E. Prophylaxis (Table 15) Table 15. Endocarditis Prophylaxis Conditions in Which Prophylaxis Is Necessary Prosthetic cardiac valves including bioprosthetic and homograft valves Previous bacterial endocarditis Congenital heart disease Unrepaired cyanotic congenital heart disease Completely repaired congenital heart defect with prosthetic material or device, during the first 6 months after the procedure Repaired congenital heart disease with residual defects adjacent to or at the site of a prosthetic patch or device Cardiac transplant recipients who develop cardiac valvulopathy Dental Procedures That Require Prophylaxis Any dental procedure that involves the gingival tissues or periapical region of a tooth and for procedures that perforate the oral mucosa Other Procedures That Require Prophylaxis Respiratory tract Tonsillectomy or adenoidectomy Surgical operations that involve an incision or biopsy of the respiratory mucosa ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-225 Infectious Diseases I F. Recommended Prophylaxis for Dental or Respiratory Tract Procedures (Table 16) Table 16. Prophylaxis for Dental or Respiratory Tract Procedures Situation Agent Regimen Standard general prophylaxis Unable to take oral medications Amoxicillin Ampicillin Adults: 2 g; children: 50 mg/kg 1 hr before procedure Adults: 2 g IM/IV; children: 50 mg/kg IM/IV within 30 min before procedure Adults: 1 g IM/IV; children: 50 mg/kg IM/IV within 30 minutes before procedure Adults: 600 mg; children: 20 mg/kg 1 hr before procedure Adults: 2 g; children: 50 mg/kg 1 hr before procedure Adults: 500 mg; children: 15 mg/kg 1 hr before procedure Cefazolin or ceftriaxone Allergic to penicillin Clindamycin Cephalexin Azithromycin or clarithromycin Allergic to penicillin and unable Clindamycin to take oral medications Cefazolin or ceftriaxone Adults: 600 mg; children: 20 mg/kg IV within 30 min before procedure Adults: 1 g IM/IV; children: 50 mg/kg IM/IV within 30 min before procedure IM = intramuscularly; IV = intravenously. Patient Case 10. Six months after treatment of his endocarditis, T.S. is visiting his dentist for a tooth extraction. Which antibiotic is best for prophylaxis? A. Tooth extractions do not warrant endocarditis prophylaxis. B. Administer amoxicillin 2 g 1 hour before the extraction. C. Administer amoxicillin 3 g 1 hour before the extraction and 1.5 g 6 hours for four doses after the extraction. D. T.S. is not at increased risk of endocarditis and does not need prophylactic antibiotics. VIII. PERITONITIS AND INTRA-ABDOMINAL INFECTIONS A. Introduction 1. Definition: Inflammation of the peritoneum (serous membrane lining the abdominal cavity) 2. Types a. Primary: Spontaneous or idiopathic, no primary focus of infection b. Secondary: Occurs secondary to an abdominal process B. Primary Peritonitis: Spontaneous Bacterial Peritonitis (see the “Gastrointestinal Disorders” chapter) C. Secondary Peritonitis 1. Etiology: a. Peptic ulcer perforation b. Perforation of a GI organ c. Appendicitis d. Endometritis secondary to intrauterine device e. Bile peritonitis f. Pancreatitis ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-226 Infectious Diseases I g. Operative contamination h. Diverticulitis i. Intestinal neoplasms j. Secondary to peritoneal dialysis 2. Microbiology of intra-abdominal infections a. Stomach and proximal small intestine: Aerobic and facultative gram-positive and gram-negative organisms b. Ileum: E. coli, Enterococcus, anaerobes c.  Large intestine: Obligate anaerobes (i.e., Bacteroides, Clostridium perfringens), aerobic and facultative gram-positive and gram-negative organisms (i.e., E. coli, Streptococcus, Enterococcus, Klebsiella, Proteus, Enterobacter) 3. Clinical manifestations and diagnosis a. Fever, tachycardia b. Elevated WBC c. Abdominal pain aggravated by motion, rebound tenderness d. Bowel paralysis e. Pain with breathing f. Decreased renal perfusion g. Ascitic fluid i. Protein: High (more than 3 g/dL); exudate fluid ii. WBCs: Many, primarily granulocytes D. Therapy: Secondary Peritonitis 1. Therapy or prophylaxis should be limited in a. Bowel injuries caused by trauma that are repaired within 12 hours (treat for less than 24 hours) b. Intraoperative contamination by enteric contents (treat for less than 24 hours) c. Perforations of the stomach, duodenum, and proximal jejunum (unless patient is on antacid therapy or has malignancy) (prophylactic antibiotics for less than 24 hours) d. Acute appendicitis without evidence of perforation, abscess, or peritonitis (treat for less than 24 hours) 2. Mild to moderate community-acquired infection a. Cefoxitin b. Cefazolin plus metronidazole or cefuroxime plus metronidazole or ceftriaxone plus metronidazole c. Ertapenem d. Moxifloxacin e. Ciprofloxacin plus metronidazole or levofloxacin plus metronidazole f. Tigecycline 3. High-risk or severe* community-acquired or health care–acquired infection (*High-risk or severe is defined as APACHE II score greater than 15, advanced age, poor nutritional status/low albumin concentration, comorbidities and organ dysfunction, an inability to achieve adequate source control, presence of malignancy, severe physiologic disturbance, or immunosuppression.) a. Piperacillin/tazobactam b. Ceftazidime plus metronidazole or cefepime plus metronidazole c. Imipenem/cilastatin or meropenem d. Ciprofloxacin plus metronidazole or levofloxacin plus metronidazole (not for health care–acquired infections) e. Consider adding an aminoglycoside when extended-spectrum β-lactamase–producing Enterobacteriaceae or P. aeruginosa is of concern (health care–acquired infections only) f. Consider adding vancomycin for MRSA (health care–acquired infections only) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-227