Infections Due to Pseudomonas, Burkholderia, and Stenotrophomonas Species¶

Chapter 170 | Part 5 – Infectious Diseases: Bacterial · Part 5 – Infectious Diseases: Bacterial · Chapter 170

Key Clinical Points¶

P. aeruginosa is the most common gram-negative bacteremia cause in neutropenic patients in parts of Asia and Latin America.
P. aeruginosa remains the leading cause of respiratory failure and mortality in cystic fibrosis (CF) patients.
Burkholderia pseudomallei and B. mallei are primary pathogens, while other species are opportunists.
Stenotrophomonas maltophilia is an opportunistic pathogen that overgrows with broad-spectrum antibiotic use.
P. aeruginosa virulence factors include pili, flagella, LPS, and exotoxins (ExoU, ExoS), but host compromise is required for infection.
ICUs are the primary setting for P. aeruginosa infections due to multiple predisposing factors.

1. DEFINITION & OVERVIEW¶

Pseudomonas, Burkholderia, and Stenotrophomonas species are gram-negative bacteria that cause opportunistic infections in immunocompromised hosts.

Definition (Harrison's 22e): Pseudomonas aeruginosa is a nonfastidious, motile, gram-negative rod that grows on most common laboratory media and produces yellow to dark green pigments.

Definition (Harrison's 22e): Stenotrophomonas maltophilia is a strictly opportunistic pathogen that overgrows in the setting of broad-spectrum antibiotic use.

1.1 Taxonomy and Classification¶

• Pseudomonas: The genus contains >140 species; P. aeruginosa is the most clinically significant. • Burkholderia: Comprises >20 species, including B. pseudomallei (melioidosis) and B. mallei (glanders). • Stenotrophomonas: Contains one medically important species: S. maltophilia.

2. EPIDEMIOLOGY¶

• Environmental Presence: P. aeruginosa is ubiquitous in moist environments (soil, water, plants) but requires host compromise for infection. • Clinical Setting: ◦ ICUs are the primary setting due to factors like mechanical ventilation and antibiotic use. ◦ Cystic Fibrosis: P. aeruginosa remains the leading cause of respiratory failure and mortality despite declining incidence in other populations.

2.1 Risk Factors¶

• Host Compromise: Neutropenia, burns, and chronic lung disease. • Clinical Context: ICU admission is the primary risk factor due to the convergence of multiple predisposing factors (e.g., mechanical ventilation, broad-spectrum antibiotic use).

3. PATHOGENESIS¶

• Virulence Factors: P. aeruginosa virulence depends on adhesion (pili, flagella), LPS-mediated inflammation, and exotoxins. • Host Interaction: Host compromise is required for infection despite the organism's metabolic versatility. • S. maltophilia Behavior: Thrives in antibiotic-altered microbiota but lacks competitive advantage in the gut.

3.1 Virulance Mechanisms (Table 170-1)¶

• Pili: Adhesion to cells. • Flagella: Adhesion, motility, inflammation. • Lipopolysaccharide (LPS): Antiphagocytic activity, inflammation. • Type III secretion system: Toxic activity (ExoU, ExoS). • Type II secretion system: Toxic activity. • Proteases: Proteolytic activity. • Phospholipases: Cytotoxicity. • Exotoxin A: Cytotoxicity. • Pyocyanin: Cytotoxicity.

4. CLINICAL MANIFESTATIONS¶

• P. aeruginosa: ◦ Burn wound sepsis ◦ Ventilator-associated pneumonia ◦ Urinary tract infections (UTI) ◦ Cystic Fibrosis: Chronic lung infections leading to respiratory failure. • B. cepacia complex: ◦ Chronic lung infection in CF. ◦ Melioidosis (rarely outside endemic regions). • S. maltophilia: ◦ Nosocomial infections (e.g., bacteremia, pneumonia) in neutropenic or antibiotic-treated patients.

5. DIAGNOSTIC APPROACH¶

• Laboratory Identification: ◦ P. aeruginosa: Shiny 'gun-metal' colonies with fruity odor; non-lactose fermenting on MacConkey agar. ◦ S. maltophilia: Resistant to multiple antibiotics (e.g., trimethoprim-sulfamethoxazole, ceftazidime). • Special Features: ◦ CF isolates may show mucoid phenotype due to alginate overproduction. ◦ Molecular methods (multiplex PCR) enable rapid detection in respiratory/blood samples.

6. TREATMENT¶

Bacteremia Management (Table 170-2): • Nonneutropenic host: ◦ Options: Ceftazidime (2 g q8h), Cefepime (2 g q8h), Piperacillin/tazobactam (4.5 g q6h), Imipenem (500 mg q6h), Meropenem (1–2 g q8h), or Doripenem (500 mg q8h). ◦ Add Amikacin (7.5 mg/kg q12h or 15 mg/kg q24h) or Tobramycin if in shock or in areas with high resistance to primary β-lactams. ◦ Duration: 6–10 days for uncomplicated cases. • Neutropenic host: ◦ Options: Cefepime (2 g q8h) or any of the above except Doripenem. ◦ Duration: 6–8 weeks until no longer neutropenic.
Pneumonia Management (Table 170-2): • Standard: Use drugs/dosages as for bacteremia; however, carbapenems should not be the sole primary drugs due to high resistance rates. • Add-ons: Add aminoglycoside or ciprofloxacin (500–750 mg q12h PO) until sensitivities are available. • Alternative: Cefepime or Ceftazidime at same dosages as bacteremia; aminoglycosides not necessary; ciprofloxacin (500–750 mg q12h PO). • Duration: 7 days.
CNS Infection Management (Table 170-2): • Options: Ceftazidime or Cefepime (2 g q8h) or Meropenem (2 g q8h). • Local: Topical tobramycin/ciprofloxacin/levofloxacin eyedrops. • Procedure: Abscesses or other closed-space infections may require drainage. • Duration: ≥ 2 weeks.
Urinary Tract Infection (UTI) Management (Table 170-2 & 170-3): • Standard Options: Ciprofloxacin (500 mg q12h), Levofloxacin (750 mg q24h), or any aminoglycoside (total daily dose given once daily). • Alternative options: Ceftazidime or Cefepime (1 g q8h) or Piperacillin/tazobactam (3.375 g q6h; Table 3: 3.75 g q8h). • Advanced Options (Complex UTI / Pyelonephritis): ◦ Ceftazidime/avibactam (2.5 g q8h, infused over 2 h) ◦ Ceftolozane/tazobactam (1.5–3 g q8h) ◦ Imipenem/relebactam (500 mg q6h) ◦ Cefiderocol (2 g q8h) ◦ Colistin (100 mg q12h IV for shortest possible period to obtain clinical response). • Duration: ◦ Uncomplicated cystitis: 3 days. ◦ Complicated cystitis and uncomplicated pyelonephritis: 5–7 days.
Burkholderia cepacia complex Management (Table 170-2): • Option A: Meropenem (2 g q8h) or TMP-SMX (1600/320 mg q12h) for 14 days. • Option B: Ceftazidime (2 g q6h), Meropenem (1 g q8h), or Imipenem (500 mg q6h) for 2 weeks → TMP-SMX (1600/320 mg q12h) for 3 months. • Note: Do not use these agents in combination due to possible antagonism.
Stenotrophomonas maltophilia Management (Table 170-2 & 170-3): • Standard: TMP-SMX (1600/320 mg q12h) plus either Levofloxacin (750 mg q24h), Minocycline (100–200 mg q12h), or Ticarcillin/clavulanate (3.1 g q4h) for 7 to 14 days. • XDR Strains: Ceftazidime-avibactam plus aztreonam, cefiderocol, or tigecycline; alternatives include ceftazidime, ticloxacillin, or cyprocycline. • Note: Combination therapy should be used for bacteremia, especially in immunosuppressed patients.
Special Cases (Table 170-3): • Keratitis/Ulcer: Topical tobramycin/ciprofloxacin/levofloxine; duration 2 weeks or until resolution of eye lesions. • Endophthalmitis: Ceftazidime or Cefepime plus fluoroquinolone therapy. • Melioidosis (B. pseudomallei): Meropenem (1 g q8h) or Imipenem (600 mg q8h) for 2 weeks → TMP-SMX (1600/200 mg q12h) for 10 months. • MDR/XDR P. aeruginosa: Cefiderocol (2.5 g q8h), Ceftolozane/tazobactam (1.5–3 g q8h), Imipenem (1 g q8h), Meropenem (1 g q8h), Linezolid (600 mg q12h), or Piperacillin/tazobactam (4.5 g q8h). Use shortest possible period to obtain clinical response.

7. PROGNOSIS AND PREVENTION¶

• P. aeruginosa: ◦ Mortality from bacteremia: 30–50% in ICU patients. ◦ Cystic Fibrosis: Leads to progressive respiratory failure. • B. pseudomallei: ◦ Case fatality rate: ~10–20% with appropriate treatment. • S. maltophilia: ◦ Prognosis depends on underlying comorbidities and antibiotic susceptibility.

KEY PEARLS & HIGH-YIELD POINTS¶

• Ecthyma Gangrenosum: A critical clinical sign of systemic infection/sepsis in immunocompromised patients (Figure 170-1). • S. maltophilia: Often results from broad-spectrum antibiotic use; requires combination therapy for bacteremia in immunosuppressed patients. • B. pseudomallei: Requires prolonged treatment (6–12 weeks) with ceftazidime or meropenem; avoid aminoglycosides in severe disease. • P. aeruginosa: High mortality rates despite modern therapies; management depends on site of infection (e.g., 7 days for pneumonia vs. 6–8 weeks for neutropenic bacteremia).

Reference Tables¶

TABLE 170-1 Main Putative Virulence Factors of Pseudomonas aeruginosa¶

Harrison's 22e, p.1307

SUBSTANCE/ ORGANELLE	FUNCTION	VIRULENCE IN ANIMAL DISEASE
Pili	Adhesion to cells	?
	Adhesion, motility, inflammation
Lipopolysaccharide	Antiphagocytic activity, inflammation	Yes
	Toxic activity (ExoU, ExoS)
Type II secretion system	Toxic activity	Yes
	Proteolytic activity
Phospholipases	Cytotoxicity	?
	Cytotoxicity
Pyocyanin	Cytotoxicity	Yes

Harrison's 22e, p.1309

INFECTION	ANTIBIOTICS AND DOSAGES	OTHER CONSIDERATIONS
Bacteremia
Nonneutropenic host	Ceftazidime (2 g q8h IV) or cefepime (2 g q8h IV) or piperacillin/tazobactam (4.5 g q6h IV) or imipenem (500 mg q6h IV) or meropenem (1–2 g q8h IV) or doripenem (500 mg q8h IV) Optional: Amikacin (7.5 mg/kg q12h or 15 mg/kg q24h IV)	Add an aminoglycoside empirically for patients in shock and in regions or hospitals where rates of resistance to the primary β-lactam agents are high. Tobramycin may be used instead of amikacin (susceptibility permitting). A duration of 6–10 days of therapy can be used for uncomplicated bacteremia.
Neutropenic host	Cefepime (2 g q8h IV) or any of the other agents above (except doripenem) in the above dosages	Febrile neutropenic patients should be treated until no longer neutropenic.
	Antibiotic regimens as for bacteremia for 6–8 weeks
Pneumonia	Drugs and dosages as for bacteremia, except that the available carbapenems should not be the sole primary drugs because of high rates of resistance during therapy.	Add aminoglycoside or ciprofloxacin, as for bacteremia, until sensitivities available. The duration of therapy is 7 days.
	Cefepime or ceftazidime at the same dosages as for bacteremia; aminoglycosides not a necessary component of therapy; ciprofloxacin (500–750 mg q12h PO) may be used
Central nervous system infection	Ceftazidime or cefepime (2 g q8h IV) or meropenem (2 g q8h IV)	Abscesses or other closed-space infections may require drainage. The duration of therapy is ≥2 weeks.
	Topical therapy with tobramycin/ciprofloxacin/levofloxacin eyedrops
	Ceftazidime or cefepime as for central nervous system infection plus Topical therapy
Urinary tract infection (UTI)	Ciprofloxacin (500 mg q12h PO) or levofloxacin (750 mg q24h) or any aminoglycoside (total daily dose given once daily). Cefepime or ceftazidime (1g q8h) or piperacillin/tazobactam (3.375 g q6h)	Uncomplicated cystitis may be treated for 3 days with oral agents. Relapse may occur if an obstruction or a foreign body is present. The duration of therapy for complicated cystitis and uncomplicated pyelonephritis is 5–7 days.
	Ceftazidime/avibactam (2.5 g q8h, infused over 2 h) or ceftolozane/tazobactam (1.5–3 g q8h) or imipenem/ relebactam (500 mg q6h) or cefiderocol (2 g q8h) or colistin (100 mg q12h IV for the shortest possible period to obtain a clinical response)
Burkholderia cepacia complex infection	Meropenem (2 g q8h IV) or TMP-SMX (1600/320 mg q12h IV) for 14 days	Resistance to both agents is increasing. Do not use them in combination because of possible antagonism.
	Ceftazidime (2 g q6h) or meropenem (1 g q8h) or imipenem (500 mg q6h) for 2 weeks followed by TMP-SMX (1600/320 mg q12h PO) for 3 months
Stenotrophomonas maltophilia infection	TMP-SMX (1600/320 mg q12h IV) plus either levofloxacin (750 mg q24h) or minocycline (100-200 mg q12h) or ticarcillin/clavulanate (3.1 g q4h IV) for 7 to 14 days	Broad-spectrum antibiotic therapy leads to respiratory tract colonization and often warrants no treatment. Ceftazidime- avibactam plus aztreonam, cefiderocol, or tigecycline are alternatives for XDR strains. Combination therapy should be used for bacteremia, especially in immunosuppressed patients.