3.2 Infectious Diseases: Common & Severe Infections

Common & Severe Infections

Pneumonia

Community-Acquired Pneumonia (CAP)

The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines stratify empiric treatment of CAP based on the presence of comorbidities, risk factors for MRSA or Pseudomonas aeruginosa, and the severity of illness. Clinical severity scoring systems such as the Pneumonia Severity Index (PSI) and the CURB-65 score (Confusion, Uremia, Respiratory rate $\ge$ 30, Blood pressure < 90/60, Age $\ge$ 65) are recommended to objectively guide site-of-care decisions. Procalcitonin (PCT), a biomarker elevated in bacterial infections but not viral infections, is increasingly utilized to guide safe de-escalation and early discontinuation of antibiotics. Common pathogens include Streptococcus pneumoniae, Haemophilus influenzae, and atypicals (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila).

Outpatient Empiric Therapy:

• No comorbidities or risk factors for MRSA/Pseudomonas:
  • Amoxicillin 1g PO TID, OR
  • Doxycycline 100 mg PO BID, OR
  • Macrolide (azithromycin or clarithromycin) only if local pneumococcal resistance is < 25%.
• With comorbidities (e.g., chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; asplenia):
  • Combination therapy: Amoxicillin/clavulanate or a third-generation cephalosporin (cefpodoxime, cefuroxime) PLUS a macrolide or doxycycline.
  • Monotherapy: Respiratory fluoroquinolone (levofloxacin, moxifloxacin, or gemifloxacin).

Inpatient Empiric Therapy (Non-Severe):

• Combination therapy: Beta-lactam (ceftriaxone, cefotaxime, ampicillin-sulbactam, or ceftaroline) PLUS a macrolide (azithromycin) or doxycycline.
• Monotherapy: Respiratory fluoroquinolone (levofloxacin or moxifloxacin). Note that ciprofloxacin is not a respiratory fluoroquinolone due to inadequate S. pneumoniae coverage.

Inpatient Empiric Therapy (Severe CAP / ICU Admission):

• Regimen: A beta-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) PLUS either an IV macrolide (azithromycin) or an IV respiratory fluoroquinolone. Monotherapy is strictly contraindicated in severe CAP.
• If the patient has validated risk factors for Pseudomonas (prior isolation of P. aeruginosa from the respiratory tract) or MRSA (prior MRSA infection, recent IV antibiotics, recent hospitalization), the empiric regimen must be broadened accordingly (e.g., cefepime + levofloxacin + vancomycin).

Hospital-Acquired (HAP) and Ventilator-Associated Pneumonia (VAP)

HAP occurs $\ge$ 48 hours after hospital admission without intubation, while VAP arises $\ge$ 48 hours after endotracheal intubation. The primary concern shifts heavily to multi-drug resistant (MDR) pathogens, particularly MRSA and non-fermenting Gram-negative rods like Pseudomonas aeruginosa and Acinetobacter baumannii.

Risk Factors for MDR VAP: Intravenous antibiotic use within the past 90 days, septic shock at the time of VAP onset, acute respiratory distress syndrome (ARDS) preceding VAP, and 5 or more days of hospitalization prior to the occurrence of VAP.

Empiric Regimen Selection:

1. MRSA Coverage: Recommended if the patient has risk factors for antimicrobial resistance, is treated in a unit where >10-20% of S. aureus isolates are MRSA, or if the prevalence is unknown. Use vancomycin or linezolid. (Daptomycin cannot be used due to surfactant binding).
2. Antipseudomonal Coverage: All HAP/VAP empiric regimens require at least one antipseudomonal agent (e.g., piperacillin-tazobactam, cefepime, ceftazidime, meropenem, or levofloxacin).
3. Double Antipseudomonal Coverage: Indicated for VAP patients with risk factors for MDR pathogens, high risk of mortality (e.g., septic shock, need for ventilatory support), or in units with > 10% resistance to monotherapy options. The two agents must be from different classes with different mechanisms of action (e.g., a beta-lactam + an aminoglycoside, or a beta-lactam + a fluoroquinolone).

Bacterial Meningitis

Bacterial meningitis is a catastrophic neurologic emergency. Delays in appropriate antibiotic therapy are directly associated with increased mortality, irreversible neurologic deficits, and hearing loss. A lumbar puncture (LP) should be performed immediately, but antibiotics must never be delayed if the LP is contraindicated (e.g., due to coagulopathy or mass effect) or technically delayed.

CSF Analysis (Bacterial vs. Viral)

• Bacterial Meningitis: Turbid appearance, elevated opening pressure, significantly elevated WBC count (> 1000 cells/mm$^3$) with a polymorphonuclear (PMN) neutrophil predominance, low glucose (< 40 mg/dL, or CSF:serum ratio < 0.4), and highly elevated protein (> 100 mg/dL).
• Viral (Aseptic) Meningitis: Clear appearance, normal to slightly elevated WBC (< 500 cells/mm$^3$) with a lymphocyte predominance, normal glucose, and normal to mildly elevated protein.

Empiric Therapy by Age Group

• Age 2 to 50 years: S. pneumoniae, Neisseria meningitidis.
  • Regimen: Ceftriaxone 2g IV q12h (or cefotaxime) PLUS Vancomycin (to aggressively cover highly penicillin-resistant S. pneumoniae until MICs are known).
• Age > 50 years, immunocompromised, or pregnant: Increased risk for Listeria monocytogenes.
  • Regimen: Ceftriaxone PLUS Vancomycin PLUS Ampicillin 2g IV q4h (specifically for Listeria).

Adjunctive Dexamethasone: Dexamethasone 0.15 mg/kg IV q6h for 4 days is recommended to mitigate the severe inflammatory response triggered by bacterial lysis in the subarachnoid space. It must be administered 10-20 minutes prior to, or at least concomitant with, the first dose of antibiotics. It is primarily beneficial in adults with pneumococcal meningitis. If CSF cultures ultimately reveal a pathogen other than S. pneumoniae, dexamethasone is typically discontinued early.

Severe Beta-Lactam Allergy: For patients with a history of anaphylaxis to beta-lactams, the ceftriaxone and ampicillin must be replaced. A standard, guideline-supported alternative is Vancomycin + Moxifloxacin (or Levofloxacin) + TMP-SMX (to provide bactericidal coverage for Listeria).

Healthcare-Associated/Post-Neurosurgical Meningitis: Following neurosurgery or the placement of an external ventricular drain, pathogens shift to include Staphylococcus species (including MRSA, Coagulase-negative Staph) and aerobic Gram-negative bacilli (including Pseudomonas).

• Regimen: Vancomycin PLUS an antipseudomonal beta-lactam with robust CNS penetration (Cefepime, Ceftazidime, or Meropenem). Piperacillin-tazobactam is explicitly avoided due to inadequate penetration across the blood-brain barrier.

Urinary Tract Infections (UTI)

Asymptomatic Bacteriuria

Defined as the presence of bacteria in the urine in the absence of signs or symptoms referable to a UTI. General Rule: Do not screen for or treat asymptomatic bacteriuria. Routine treatment drives antimicrobial resistance and increases the risk of C. difficile. Exceptions: Treatment is strictly indicated only for pregnant women (due to the risk of pyelonephritis, premature delivery, and low birth weight) and patients undergoing urologic procedures involving mucosal bleeding.

Uncomplicated Cystitis

Occurs in healthy, non-pregnant women with no structural or functional abnormalities of the urinary tract. Common pathogens are E. coli (>80%), Klebsiella pneumoniae, and Staphylococcus saprophyticus.

• First-line Options:
  1. Nitrofurantoin monohydrate/macrocrystals 100 mg PO BID for 5 days (Avoid if CrCl < 30 mL/min).
  2. Trimethoprim-sulfamethoxazole (TMP-SMX) DS 1 tablet PO BID for 3 days (Avoid if local E. coli resistance exceeds 20%).
  3. Fosfomycin tromethamine 3g PO as a single dose (Inferior efficacy to nitrofurantoin/TMP-SMX in some comparative trials, but highly useful for ESBL cystitis).
• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved as alternative agents due to "collateral damage" (e.g., tendon rupture, QTc prolongation, neuropathy, CDI).

Pyelonephritis

Infection of the upper urinary tract (kidneys). Nitrofurantoin and fosfomycin must not be used because they do not achieve adequate tissue concentrations in the renal parenchyma; they simply concentrate in the bladder.

• Outpatient Therapy:
  • Ciprofloxacin 500 mg PO BID for 7 days or Levofloxacin 750 mg PO daily for 5 days (Preferred only if local community resistance is < 10%).
  • If fluoroquinolone resistance is > 10%, give a one-time IV dose of a long-acting beta-lactam (Ceftriaxone 1g) or a 24-hour consolidated dose of an aminoglycoside (e.g., Tobramycin or Gentamicin 5-7 mg/kg) prior to discharging the patient on oral fluoroquinolones, TMP-SMX, or oral beta-lactams.

Catheter-Associated UTI (CAUTI)

The presence of symptoms (fever, altered mental status, flank pain) combined with a positive urine culture in a patient with an indwelling urinary catheter.

• Management: Remove or exchange the catheter if it has been in place for > 2 weeks prior to initiating antimicrobials. Treat for 7 days if prompt resolution of symptoms occurs, or 10-14 days for a delayed clinical response.