Pseudomonas & Nonfermenting Gram-Negative Rods

Identification and virulence of P. aeruginosa

Lab profile. Pseudomonas aeruginosa is a motile, aerobic gram-negative rod that is oxidase-positive and catalase-positive. As a nonfermenter it makes energy by oxidative metabolism and ferments neither lactose nor glucose, so it forms pale (non-lactose-fermenting) colonies on MacConkey agar. Cultures give off a sweet odor likened to grapes or corn tortillas. Proteus also spares lactose, but it is oxidase-negative.

Pigments. Pyocyanin, a blue-green phenazine, redox-cycles to generate reactive oxygen species (superoxide and hydrogen peroxide) that injure host cells and slow ciliary beating. Pyoverdine is a yellow-green fluorescent siderophore that captures iron. Together they tint pus and burn dressings green.

Biofilm and cystic fibrosis. In the CF airway, Pseudomonas switches on alginate production (partly under quorum-sensing control), building a biofilm that shields it from antibiotics, antibodies, and neutrophils. Mucoid strains signal chronic, practically ineradicable infection. The same biofilm coats catheters, endotracheal tubes, and contact lenses. Inhaled tobramycin or inhaled aztreonam is used to suppress chronic infection in CF.

Water-loving infections and compromised hosts

Where it lives. Pseudomonas thrives wherever there is moisture: hot tubs, pools, contact-lens cases, sneaker insoles, and, in hospitals, sinks, respiratory circuits, and fluids.

A contact-lens wearer with a painful red eye needs urgent eye care and antipseudomonal drops (such as a fluoroquinolone); never patch a corneal abrasion in a lens wearer, because Pseudomonas keratitis can perforate the cornea within days.

Malignant otitis externa. Older diabetics develop severe, persistent ear pain and otorrhea with granulation tissue in the external canal. Infection spreads to the temporal bone and skull base, causing osteomyelitis and cranial nerve palsies, often the facial nerve first. CT or MRI defines the extent, and treatment is a prolonged course (often 6–8 weeks) of antipseudomonal therapy.

Sneaker puncture. A nail through a rubber-soled sneaker inoculates Pseudomonas from the moist foam, producing osteomyelitis or osteochondritis of the foot days to weeks later. S. aureus remains the most common cause of osteomyelitis overall.

Ecthyma gangrenosum. In neutropenic patients, bacteremia invades the walls of small dermal vessels: a red macule becomes a hemorrhagic bulla and then a necrotic black eschar with a red halo. It demands immediate antipseudomonal therapy.

Hospital infections. Pseudomonas is a leading cause of ventilator-associated and hospital-acquired pneumonia, catheter-associated UTI, burn-wound infection, and bacteremia. Febrile neutropenia is therefore treated empirically with an antipseudomonal β-lactam such as cefepime, piperacillin-tazobactam, or meropenem.

Antipseudomonal therapy and intrinsic resistance

Drugs that cover Pseudomonas.

• β-lactams — piperacillin-tazobactam, ceftazidime, cefepime, imipenem and meropenem, and aztreonam. Newer options for multidrug-resistant strains include ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol.
• Fluoroquinolones — ciprofloxacin and levofloxacin, the only oral antipseudomonal class; moxifloxacin is unreliable.
• Aminoglycosides — gentamicin, tobramycin, amikacin (nephrotoxicity, ototoxicity).
• Polymyxins — colistin and polymyxin B, reserved for resistant strains (nephrotoxicity, neurotoxicity).

Ertapenem is the carbapenem without activity against Pseudomonas or Acinetobacter. Ampicillin-sulbactam, ceftriaxone, and cefazolin do not cover Pseudomonas either.

Aztreonam. This monobactam is the antipseudomonal choice in severe penicillin allergy; it cross-reacts only with ceftazidime, which shares its side chain.

Intrinsic resistance. The outer membrane has few, restrictive porins, so drugs enter slowly; multidrug efflux pumps expel many classes; and a chromosomal inducible AmpC β-lactamase inactivates many β-lactams. Loss of the OprD porin gives imipenem resistance. Because resistance can emerge during therapy, susceptibility testing guides treatment.

Other nonfermenting gram-negative rods

Acinetobacter baumannii. An oxidase-negative, coccobacillary nonfermenter that survives for long periods on dry hospital surfaces. It causes ventilator-associated pneumonia, bacteremia, and infected combat wounds. Carbapenem-resistant strains are treated with polymyxins or sulbactam-based regimens (such as sulbactam-durlobactam); sulbactam, usually just a β-lactamase inhibitor, binds Acinetobacter PBPs and has its own activity.

Burkholderia cepacia complex. It spreads between people with CF, so clinics separate patients. It can cause accelerated lung decline or cepacia syndrome — fatal necrotizing pneumonia with bacteremia — and colonization can bar lung transplantation. Because it is catalase-positive, it is one of the classic infections of chronic granulomatous disease, alongside S. aureus, Serratia, Nocardia, and Aspergillus.

Burkholderia pseudomallei. Melioidosis follows exposure to soil and water in Southeast Asia and northern Australia, mainly in diabetics. It causes pneumonia, sepsis, and abscesses of liver, spleen, and prostate; gram stain may show bipolar "safety-pin" rods. It can lie latent and reactivate years later — veterans nicknamed it the "Vietnam time bomb." Treatment is IV ceftazidime or meropenem, then months of oral TMP-SMX to prevent relapse.

Stenotrophomonas maltophilia. An opportunist of ventilated, neutropenic, and catheterized patients that often emerges during carbapenem therapy, because a chromosomal metallo-β-lactamase makes it intrinsically carbapenem-resistant. TMP-SMX is the drug of choice; levofloxacin and minocycline are alternatives.