Modified Gallbladder, Liver PDF

Gallbladder Disorders Cholelithiasis (Gallstones) Definition: Formation of gallstones in the gallbladder (cholesterol or pigment stones). Risk Factors: o "5 F's": Fat, Fertile, Forty, Female, Flatulent. o Obesity, rapid weight loss, pregnancy, Crohn’s disease, med...

Gallbladder Disorders Cholelithiasis (Gallstones) Definition: Formation of gallstones in the gallbladder (cholesterol or pigment stones). Risk Factors: o "5 F's": Fat, Fertile, Forty, Female, Flatulent. o Obesity, rapid weight loss, pregnancy, Crohn’s disease, medications (e.g., octreotide, ceftriaxone). Prevention: Low-carb diet, physical activity, high-fiber diet, NSAIDs, and caffeinated coffee (in females). Symptoms: Often asymptomatic; may cause episodic RUQ pain (biliary colic). Diagnosis: o Ultrasound (US): Gold standard for gallstones. Treatment: o Asymptomatic: No treatment needed, observation. o Symptomatic: Laparoscopic cholecystectomy. o Nonsurgical candidates: Ursodeoxycholic acid (bile acid therapy). Ursodeoxycholic Acid: MOA: Reduces cholesterol saturation in bile, dissolves cholesterol stones. Indication: Non-surgical candidates or prevention of stones (e.g., rapid weight loss patients). Side Effects: Diarrhea, pruritus. Clinical Pearls: Most effective for small, non-calcified cholesterol stones. Cholecystitis Definition: Inflammation of the gallbladder, often caused by gallstones (>90% of cases). Clinical Features: o Persistent RUQ pain, fever, vomiting, Murphy’s sign. o Jaundice in some cases. Diagnosis: o US: Gallbladder wall thickening (>5 mm), pericholecystic fluid, and Murphy’s sign. o HIDA scan: Confirms cystic duct obstruction. Treatment: o NPO, IV fluids, analgesics, broad-spectrum antibiotics (3rd-gen cephalosporins + metronidazole). Antibiotics for coverage of gram-negative and anaerobic bacteria: Ceftriaxone + Metronidazole: o MOA: Inhibits bacterial cell wall synthesis (ceftriaxone) and DNA synthesis (metronidazole). o Monitoring: Renal function, CBC. o Side Effects: GI upset, nephrotoxicity (ceftriaxone); metallic taste, neuropathy (metronidazole). o Clinical Pearls: Broad-spectrum; adjust dose for renal impairment. Alternatives: o Piperacillin-tazobactam (severe cases), because more broad. o Surgery: Laparoscopic cholecystectomy. Choledocholithiasis Definition: Gallstones in the common bile duct (CBD). Clinical Features: o RUQ colicky pain, fever, jaundice (Charcot’s triad). o If altered mental status and hypotension (Reynolds’ pentad), suspect acute suppurative cholangitis. Diagnosis: o Labs: Elevated AST, ALT, ALP, and bilirubin. o Imaging: US, ERCP (gold standard for diagnosis and treatment). Treatment: o ERCP: Stone removal, stent placement. o Antibiotics: Fluoroquinolone, ampicillin, gentamicin + metronidazole. o Cholecystectomy. Antibiotics in Choledocholithiasis and Cholecystitis Antibiotics are critical in managing choledocholithiasis and cholecystitis to control secondary infections and prevent complications like sepsis and abscess formation. These conditions often involve biliary obstruction, which predisposes the biliary tract to bacterial colonization and infection. Why Specific Antibiotics Are Used Bacteria Commonly Involved in GI/Biliary Infections 1. Gram-Negative Rods: a. Escherichia coli: Most common pathogen in biliary infections. b. Klebsiella species: Frequently isolated in bile. c. Proteus and Enterobacter species: Less common but significant. 2. Anaerobes: a. Bacteroides fragilis: Often found in polymicrobial infections. 3. Enterococcus species: a. Common gram-positive cocci in biliary infections. Supplemental information: Comprehensive Review of Antibiotics for Biliary and GI Infections Ceftriaxone + Metronidazole 1. Ceftriaxone: a. MOA: A 3rd-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. b. Coverage: i. Excellent against gram-negative rods (e.g., E. coli, Klebsiella). ii. Some gram-positive organisms (e.g., Streptococcus species). c. Rationale: Targets the most common aerobic pathogens in biliary infections. d. Side Effects: i. GI upset. ii. Biliary sludging, especially in neonates (risk of gallbladder symptoms). iii. Rare risk of nephrotoxicity. e. Monitoring: i. Renal function (especially with concurrent nephrotoxins). ii. CBC for leukopenia or eosinophilia. iii. Avoid in neonates with hyperbilirubinemia (risk of kernicterus). 2. Metronidazole: a. MOA: Disrupts DNA synthesis in anaerobic bacteria by generating toxic free radicals. b. Coverage: Excellent anaerobic coverage, including Bacteroides fragilis. c. Rationale: Complements ceftriaxone by covering anaerobes in polymicrobial biliary infections. d. Side Effects: i. Metallic taste. ii. Peripheral neuropathy with prolonged use. iii. Disulfiram-like reaction with alcohol (severe nausea/vomiting). e. Monitoring: i. Neurological symptoms (e.g., tingling or numbness). ii. Avoid alcohol during treatment and for 48 hours after. 3. Clinical Considerations: a. Together, ceftriaxone and metronidazole provide synergistic coverage of aerobic and anaerobic pathogens commonly found in biliary infections. b. Used in moderate-to-severe infections, including cholecystitis and choledocholithiasis. Ampicillin-Sulbactam MOA: o Ampicillin: Inhibits bacterial cell wall synthesis. o Sulbactam: Inhibits beta-lactamase enzymes, extending the spectrum to beta-lactamase- producing organisms. Coverage: o Gram-negative rods (E. coli, Klebsiella).  o Anaerobes (Bacteroides). o Enterococcus species (one of the few options effective against this organism). Rationale: o Broad-spectrum, single-agent option when gram-positive organisms are suspected or polymicrobial infections are likely. Side Effects: o GI upset (nausea, diarrhea). o Allergic reactions (rash or anaphylaxis in penicillin-sensitive patients). Monitoring: o Renal function: Requires dose adjustment in renal impairment. o Signs of hypersensitivity. Clinical Considerations: o Effective in mild-to-moderate infections. o Broad-spectrum coverage but less potent than piperacillin-tazobactam in severe cases. Piperacillin-Tazobactam MOA: o Piperacillin: Inhibits bacterial cell wall synthesis. o Tazobactam: Beta-lactamase inhibitor, extending activity against resistant pathogens. Coverage: o Broad-spectrum: ▪ Gram-negative rods (E. coli, Klebsiella, Proteus). ▪ Anaerobes (Bacteroides fragilis). ▪ Some resistant pathogens. Rationale: o First-line for severe biliary infections or patients with sepsis due to its wide spectrum of activity. Side Effects: o Hypokalemia: Due to renal potassium loss; monitor potassium levels. o GI upset (nausea, diarrhea). o Hypersensitivity reactions (rash, anaphylaxis). Monitoring: o Renal function: Risk of acute kidney injury, especially with other nephrotoxins. o Potassium levels: Supplement as needed to avoid complications like arrhythmias. o CBC for neutropenia with prolonged use. Clinical Considerations: o Preferred in severe or polymicrobial infections, especially if sepsis or organ dysfunction is present. o Requires dose adjustment in renal impairment. Fluoroquinolones (e.g., Ciprofloxacin, Levofloxacin) MOA: Inhibits bacterial DNA gyrase and topoisomerase IV, preventing DNA replication. Coverage: o Effective against gram-negative organisms, including E. coli and Klebsiella. o No anaerobic activity (requires combination with metronidazole). Rationale: o Option for penicillin-allergic patients. o Used in combination with metronidazole for full coverage in polymicrobial infections. Side Effects: o Tendinopathy: Increased risk of tendon rupture, especially in older adults or those on corticosteroids. o QT prolongation: Risk of arrhythmias, especially with electrolyte imbalances. o CNS effects (dizziness, confusion): More common in older adults. Monitoring: o Renal function: Adjust dose in renal impairment. o ECG for QT prolongation in high-risk patients. o Symptoms of tendinopathy (early signs of tendon pain or swelling). Clinical Considerations: o Effective in mild-to-moderate infections or in patients who cannot tolerate beta-lactams. o Avoid in severe infections unless combined with metronidazole. Comparative Summary of Antibiotics Key Common Side Antibiotic Coverage Rationale Monitoring Effects Renal Gram-negative rods, Aerobic coverage for Biliary sludging, Ceftriaxone function, some gram-positive biliary pathogens GI upset CBC Anaerobic coverage Neuropathy, Metallic taste, Metronidazole Anaerobes in polymicrobial alcohol use neuropathy infections Renal Gram-negatives, Ampicillin- Broad-spectrum function, GI upset, allergic anaerobes, Sulbactam single-agent option hypersensitiv reactions Enterococcus ity Renal Piperacillin- Broad-spectrum, Severe infections or function, Hypokalemia, GI Tazobactam resistant pathogens sepsis potassium upset levels Fluoroquinolo Gram-negatives + Alternative for Renal Tendinopathy, QT nes + anaerobes (with penicillin-allergic function, QT prolongation, CNS Metronidazole metronidazole) patients interval effects Clinical Pearls Empiric Selection: Start with broad-spectrum antibiotics (e.g., ceftriaxone + metronidazole or piperacillin-tazobactam) for biliary infections until cultures narrow therapy. Severe Cases: Use piperacillin-tazobactam or carbapenems in critically ill or septic patients. Penicillin-Allergic Patients: Use fluoroquinolones combined with metronidazole. Duration: Antibiotics are typically continued for 4–7 days after source control (e.g., ERCP or cholecystectomy). Rationale for Empiric Antibiotic Selection 1. Biliary Obstruction and Infection: a. Obstruction creates a high-pressure environment, reducing bile flow and allowing bacteria to colonize and proliferate. b. Gram-negative bacteria (e.g., E. coli, Klebsiella) are typically translocated from the intestines via the portal system. c. Anaerobes become significant in polymicrobial infections. 2. Broad-Spectrum Coverage: a. Biliary infections are often polymicrobial, so empiric therapy must target gram-negative aerobes, gram-positive cocci, and anaerobes. 3. Severity of Disease: a. Mild to moderate cases: Ceftriaxone + Metronidazole or single-agent Ampicillin-Sulbactam. b. Severe cases or sepsis: Piperacillin-Tazobactam or a carbapenem for extended-spectrum coverage. GI-Related Infections Requiring Antibiotics (Supplemental information) Diverticulitis Pathophysiology: Microperforation of diverticula leads to bacterial infection. Bacteria: Polymicrobial, often E. coli and Bacteroides fragilis. Treatment: o Outpatient: Ciprofloxacin + Metronidazole. o Inpatient: Piperacillin-Tazobactam or Ertapenem. Infectious Diarrhea Bacterial Causes: o Shigella, Salmonella, Campylobacter, E. coli (e.g., EHEC, ETEC). Antibiotics (for specific cases): o Azithromycin or Ciprofloxacin: Traveler’s diarrhea. o Avoid antibiotics for EHEC (risk of hemolytic-uremic syndrome). Clostridioides difficile Infection (CDI) Pathophysiology: Antibiotic-associated disruption of gut flora allows C. difficile overgrowth. Treatment: o Mild to moderate: Vancomycin (oral) or Fidaxomicin. o Severe: High-dose oral Vancomycin ± IV Metronidazole. o Recurrent: Consider fecal microbiota transplant. Spontaneous Bacterial Peritonitis (SBP) Pathophysiology: Infection of ascitic fluid, often in cirrhosis patients. Bacteria: Gram-negative (E. coli, Klebsiella); less commonly, gram-positive (Streptococcus). Treatment: o Empiric: Cefotaxime or Ceftriaxone. o Prophylaxis: Norfloxacin or Ciprofloxacin in high-risk patients. Appendicitis Pathophysiology: Bacterial infection following luminal obstruction. Bacteria: E. coli, Bacteroides fragilis. Treatment: o Pre-surgical: Ceftriaxone + Metronidazole or Piperacillin-Tazobactam. Monitoring and Follow-Up 1. Response to Treatment: a. Resolution of fever, leukocytosis, and abdominal symptoms. b. Repeat imaging if no clinical improvement within 48–72 hours. 2. Complications: a. Persistent abscess or new infections. b. Multisystem organ failure in severe cases. 3. Antibiotic Stewardship: a. Narrow-spectrum antibiotics should be used once cultures identify pathogens. b. Avoid unnecessary prolonged antibiotic courses. Liver Disorders Alcoholic Liver Disease Pathophysiology of Severe Alcoholic Hepatitis Alcohol consumption leads to: o Direct liver injury from alcohol metabolites (e.g., acetaldehyde). o Activation of Kupffer cells and inflammatory pathways. o Recruitment of neutrophils, production of pro-inflammatory cytokines (TNF-α, IL-1, IL-6), and oxidative stress. Severe inflammation causes: o Worsening hepatocyte damage. o Cholestasis and hepatic decompensation. o Potential progression to multi-organ failure. Definition: Progression from fatty liver to hepatitis and cirrhosis due to excessive alcohol intake. Symptoms: Jaundice, hepatomegaly, anorexia, ascites, and encephalopathy. Labs: o Elevated AST > ALT (2:1 ratio), alkaline phosphatase, bilirubin. o Macrocytic anemia. Treatment: Abstinence: o Medications for Alcohol Use Disorder: ▪ Naltrexone: Reduces craving. Corticosteroids (e.g., Prednisolone): Why prednisolone? Prednisone must be converted to prednisolone by the liver, which may be impaired in cirrhosis. o MOA: Reduces inflammation by inhibiting cytokine production. o Indication: Severe alcoholic hepatitis (Maddrey’s score >32). o Monitoring: Glucose, infection risk. o Side Effects: Hyperglycemia, immunosuppression. o Clinical Pearls: Consider pentoxifylline if steroids are contraindicated. Nutritional Support: o Thiamine (to prevent Wernicke’s encephalopathy), folate, zinc. o Severe hepatitis: Corticosteroids (e.g., methylprednisolone) or pentoxifylline if steroids are CI in such cases as active infections. Viral Hepatitis Hepatitis A: o Fecal-oral route, acute only. o Diagnosis: IgM anti-HAV (acute), IgG anti-HAV (immunity). o Treatment: Supportive care; vaccination for high-risk groups. Hepatitis B: o Transmission: Blood, body fluids. o Chronic infection risks: Cirrhosis, hepatocellular carcinoma. o Prevention: Vaccination. Treatment Antiviral Therapy: o Tenofovir, Entecavir: ▪ MOA: Inhibit HBV DNA polymerase, preventing viral replication. ▪ Side Effects: Lactic acidosis (rare), renal toxicity. ▪ Monitoring: Renal function, HBV DNA levels. Hepatitis C: o Transmission: Bloodborne (e.g., IV drug use). o Prevention: Screening for high-risk groups (e.g., "baby boomers"). Treatment Direct-Acting Antivirals (DAAs): o Sofosbuvir + Velpatasvir: ▪ MOA: Inhibits viral RNA replication. ▪ Side Effects: Fatigue, headache. ▪ Monitoring: Viral RNA levels, liver enzymes. ▪ Clinical Pearls: High cure rates (>95%) with 8–12 weeks of therapy. Cirrhosis Definition: Irreversible fibrosis and nodular regeneration of the liver. Symptoms: o Early: Fatigue, weight loss, nausea. o Late: Ascites, encephalopathy, spider nevi, palmar erythema. Treatment: Manage complications: o Ascites: Spironolactone (aldosterone antagonist), furosemide. ▪ Side Effects: Hyperkalemia (spironolactone), hypokalemia (furosemide). ▪ Monitoring: Electrolytes, renal function. o Hepatic Encephalopathy: Lactulose, rifaximin. Can use together. (Synergist) ▪ Lactulose MOA: Reduces ammonia absorption in the gut. ▪ Side Effects: Diarrhea, bloating. ▪ Rifaximin MOA: Reduces ammonia-producing gut bacteria. Definitive: Liver transplant. Use of Lactulose and Rifaximin in Cirrhosis Lactulose and rifaximin are used primarily for managing hepatic encephalopathy (HE) in patients with cirrhosis. HE is a reversible neuropsychiatric syndrome caused by the accumulation of ammonia and other toxins in the bloodstream, resulting from impaired liver function. Ammonia Accumulation: The liver normally detoxifies ammonia (a byproduct of protein metabolism) into urea for excretion. In cirrhosis, impaired liver function and shunting of blood around the liver (portosystemic shunting) lead to increased ammonia levels in the bloodstream. Ammonia crosses the blood-brain barrier, causing neurotoxicity and HE symptoms (e.g., confusion, asterixis, altered consciousness). Pancreatic Disorders Acute Pancreatitis Definition: Inflammation of the pancreas. Causes: Gallstones, alcohol abuse, hyperlipidemia, medications. Symptoms: Severe epigastric pain radiating to the back, nausea, vomiting. Diagnosis: o Labs: Elevated amylase, lipase. o Imaging: US or CT. Treatment: o Supportive care: ▪ NPO: Allows the pancreas to rest. ▪ IV Fluids: Prevent hypovolemia. ▪ Analgesics: Morphine: Pain relief. Side Effects: Respiratory depression, constipation. o Antibiotics: ▪ Reserved for infected necrosis (e.g., imipenem-cilastatin). Antibiotic Therapy Antibiotics are used to treat confirmed or strongly suspected infected necrosis and to prevent systemic spread of infection. Empiric therapy should target gram-negative bacteria (e.g., E. coli, Klebsiella, Proteus) and anaerobes (e.g., Bacteroides fragilis). First-Line Antibiotics: o Carbapenems (e.g., meropenem, imipenem-cilastatin): ▪ Broad-spectrum coverage for gram-negative, gram-positive, and anaerobic organisms. ▪ Preferred due to excellent pancreatic tissue penetration. o Piperacillin-Tazobactam: ▪ Broad-spectrum, covering gram-negative and anaerobes. ▪ Alternative if carbapenems are unavailable. o Fluoroquinolone (e.g., ciprofloxacin or levofloxacin) + Metronidazole: ▪ For patients with beta-lactam allergy. ▪ Covers gram-negatives (fluoroquinolone) and anaerobes (metronidazole). Duration of Therapy: o 4–6 weeks for confirmed infected necrosis. o Shorter courses may suffice if source control is promptly achieved. Monitoring: o Clinical response (fever resolution, WBC normalization). o Blood cultures for septic patients. o Renal and hepatic function for antibiotic adjustments. Chronic Pancreatitis Definition: Chronic inflammation causing irreversible pancreatic damage. Symptoms: Chronic abdominal pain, malabsorption, steatorrhea, diabetes. Treatment: o Pain management. o Pancreatic enzyme supplementation. o Address underlying causes (e.g., stop alcohol). Treatment: Pancreatic Enzyme Replacement: o MOA: Improves digestion by supplementing lipase, protease, and amylase. o Examples: Pancrelipase. o Side Effects: Nausea, abdominal cramps. o Monitoring: Symptom improvement (steatorrhea). Pain Management: o First-line: Acetaminophen, NSAIDs. o Refractory: Tricyclic antidepressants or pregabalin. Mechanism of Pain o Chronic inflammation and fibrosis of the pancreas. o Nerve damage (neuropathic pain). o Increased pancreatic ductal pressure from strictures or stones. Management Goals o Reduce pain and improve quality of life. o Minimize opioid dependency in long-term management. Clinical Pearls In acute pancreatitis, IV opioids remain the standard for severe pain, with NSAIDs or acetaminophen as adjuncts. In chronic pancreatitis, a multimodal approach combining non-opioid analgesics, enzyme supplementation, and neuropathic pain medications is preferred. Lets talk about pain management real quick 😊 Pain Management Options 1. Non-Opioid Analgesics (First Line) a. Acetaminophen: i. Effective for mild to moderate pain. ii. Safe for long-term use if liver function is normal. b. NSAIDs (e.g., ibuprofen, naproxen): i. Reduce inflammation and pain. ii. Avoid in patients with significant renal or GI risks. 2. Opioids (Second-Line or Severe Pain) a. Examples: Tramadol, morphine, oxycodone, fentanyl. b. Used for persistent or severe pain unresponsive to other therapies. c. Clinical Pearls: i. Use the lowest effective dose to minimize dependency. ii. Tramadol is preferred for less severe cases due to its lower risk of dependency. 3. Pancreatic Enzyme Supplementation a. Examples: Pancrelipase (Creon, Zenpep). b. Indication: Pain due to pancreatic insufficiency and associated maldigestion. c. MOA: Decreases pancreatic stimulation by providing exogenous enzymes, reducing pressure within ducts. d. Clinical Pearls: Use enteric-coated formulations for better delivery. 4. Adjunctive Neuropathic Pain Medications a. Gabapentin or Pregabalin: i. MOA: Reduce neuropathic pain by modulating calcium channels in the nervous system. ii. Indication: Neuropathic pain associated with chronic pancreatitis. iii. Side Effects: Drowsiness, dizziness. b. Tricyclic Antidepressants (TCAs) (e.g., amitriptyline): i. Useful for neuropathic pain but limited by side effects. 5. Antioxidants a. Rationale: Reduce oxidative stress and inflammation in chronic pancreatitis. b. Examples: Vitamin C, selenium, methionine. c. Efficacy: Mixed evidence but considered adjunctive in selected cases. Quick Pharmacotherapy Review First-Line Condition Monitoring Clinical Pearls Medications Ursodeoxycholic Effective only for cholesterol Cholelithiasis LFTs acid stones; slow onset. Ceftriaxone + CBC, renal Cholecystitis Adjust for renal impairment. metronidazole function Choledocholith Post-ERCP Surgery post-recovery is ERCP, antibiotics iasis monitoring definitive. Alcoholic Prednisolone, Glucose, Abstinence critical for long-term Liver Disease nutritional support infection risk management. Renal function, Hepatitis B Tenofovir, entecavir Vaccination prevents infection. HBV DNA Sofosbuvir + Viral RNA, liver Hepatitis C DAAs offer high cure rates. velpatasvir enzymes Acute Electrolytes, vital Antibiotics only for infected IV fluids, morphine Pancreatitis signs necrosis. Chronic Pancrelipase, pain Symptom Emphasize alcohol cessation. Pancreatitis management resolution Why Do We Worry About Gram-Negative and Anaerobic Bugs in GI and GU Infections? Gram-negative and anaerobic bacteria are significant in gastrointestinal (GI) and genitourinary (GU) infections due to their roles in the normal flora of these systems, their pathogenicity, and the frequency of polymicrobial infections involving these organisms. Role of Gram-Negative and Anaerobic Organisms in GI Infections Gram-Negative Pathogens 1. Common Gram-Negative Bacteria in GI Infections: Escherichia coli: o Most common organism in intra-abdominal infections and UTIs originating from the GI tract. Klebsiella species: o Often associated with biliary infections and liver abscesses. Proteus species: o Contributes to GI-origin UTIs or infections associated with GI instrumentation. Pseudomonas aeruginosa: o Often found in hospital-acquired infections and postoperative abdominal infections. Enterobacter species: o Common in healthcare-associated intra-abdominal infections. 2. Why Gram-Negatives Are Critical in GI Infections: Prevalence: Dominant flora in the gut, especially the large intestine. Virulence: o Produce toxins (e.g., lipopolysaccharides in E. coli) that trigger inflammation. o Adhesion factors help colonize tissues and invade surrounding structures. Antimicrobial Resistance: o Many are multidrug-resistant (e.g., ESBL-producing organisms), complicating treatment. Anaerobic Pathogens 1. Common Anaerobic Bacteria in GI Infections: Bacteroides fragilis: o Most prevalent anaerobe in intra-abdominal infections, especially in abscesses. Clostridium species (e.g., Clostridium perfringens, C. difficile): o Causes gas gangrene and pseudomembranous colitis. Prevotella and Fusobacterium species: o Frequently found in deep-seated infections like peritoneal abscesses. 2. Why Anaerobes Are Critical in GI Infections: Thrive in oxygen-poor environments (e.g., peritoneal fluid, abscesses). Produce enzymes that degrade tissue and facilitate bacterial spread. Often found in polymicrobial infections, contributing to severity and resistance. GI Infections Involving Gram-Negative and Anaerobic Bacteria 1. Peritonitis Primary Peritonitis: o Monomicrobial infection, typically caused by E. coli or Klebsiella. Secondary Peritonitis: o Polymicrobial infection following bowel perforation, involving gram-negatives (E. coli) and anaerobes (Bacteroides). Treatment: o Ceftriaxone + Metronidazole or Piperacillin-Tazobactam for broad-spectrum coverage. 2. Appendicitis Often caused by a combination of gram-negatives and anaerobes (e.g., E. coli and Bacteroides fragilis). Treatment: o Ceftriaxone + Metronidazole or a single agent like Ertapenem. 3. Diverticulitis Associated with micro-perforations of the colon. Common organisms: E. coli and Bacteroides species. Treatment: o Outpatient: Ciprofloxacin + Metronidazole. o Inpatient: Piperacillin-Tazobactam or carbapenem. 4. Liver Abscess Pyogenic abscesses: o Caused by gram-negatives (E. coli, Klebsiella) and anaerobes. Treatment: o Empiric broad-spectrum therapy with ceftriaxone + metronidazole or meropenem. 5. Clostridioides difficile Infection (CDI) Anaerobic Clostridioides difficile causes pseudomembranous colitis. Treatment:  o Vancomycin (oral) or fidaxomicin for mild to moderate cases. o Add metronidazole (IV) for fulminant disease. 6. GI Perforation Polymicrobial infections with gram-negatives and anaerobes following bowel perforation. Treatment: o Broad-spectrum agents (e.g., piperacillin-tazobactam, imipenem-cilastatin). Connecting Gram-Negative and Anaerobes in GU Infections The close anatomical relationship between the GI and GU systems leads to crossover of pathogens, especially in: 1. UTIs from GI Flora: a. E. coli, Klebsiella, and Proteus species from the gut are the most common causes of UTIs. 2. Fournier’s Gangrene: a. Polymicrobial necrotizing fasciitis of the perineum caused by GI flora (gram-negatives and anaerobes). 3. Ascending Infections: a. GU infections such as pyelonephritis may involve gram-negative organisms originating from the GI tract. Antibiotic Treatment Principles 1. Gram-Negative Coverage: a. Ceftriaxone, piperacillin-tazobactam, or carbapenems. 2. Anaerobic Coverage: a. Metronidazole (preferred for anaerobes). b. Beta-lactam/beta-lactamase inhibitors (e.g., piperacillin-tazobactam) cover anaerobes effectively. 3. Combination Therapy: a. Used for polymicrobial infections (e.g., ceftriaxone + metronidazole). 4. Tailor Therapy: a. Base definitive therapy on culture and sensitivity results to avoid resistance.