Griebel explains that for Mannheimia infections, for example, recruitment of neutrophils is a death sentence, because they can activate a massive inflammatory response causing the destruction of lung tissue. “As a clinical veterinarian, you may not know what’s in that lung. If you knew that it was Mannheimia, then an anti-inflammatory may be absolutely critical. But if there is a Pasteurella multocida infection and it’s being contained by neutrophils, then treating with a corticosteroid may cause the Pasteurella multocida to spread through the lung. We’re dealing with a multi-factorial disease in terms of etiology and many of these therapeutic interventions may be very good for one bacterial infection and may make the disease much worse for another one. We just don’t have the diagnostic tools to know what’s down in that lung.”
And even the right drugs won’t restore the lung to its original state. “Some people buying and using antimicrobial therapies think they are making the lung all new again, that it restores normal function, but it doesn’t,” Hunsaker says. “That’s a tough concept to get across. Once irreversible damage hasbeen done, we just want to minimize that. You may get sudden death of an animal that was treated three months ago. That lung probably supported a 400- or a 500-pound carcass, but it doesn’t support an 800-pound carcass and that’s frustrating for the managers because they’ve spent money on therapy.”
MICs and sensitivity testing
For antibiotics to be effective, it is necessary to maintain a minimum inhibitory concentration. “We must consider the pharmacokinetics of antibiotic therapy,” Griebel states. “I think the failures in lung delivery are often about timing of treatment. When bacteria in the lung enter log-phase growth, we’re fighting a losing battle.” If we treat too early and our minimum inhibitory concentration has dropped, or if we come in too late and the extent of lung damage has reached a point where antibiotics can’t enter the site of infection, then their efficacy is compromised.
And if you’re too early, Hunsaker adds, you may disrupt or interfere with the commensal population to the extent that you allow an opportunity for pathogens to invade.
What frustrates Lukasiewicz are MIC and sensitivity levels of antibiotics. “You can have in vitro MICs that indicate resistance, but then you use the antibiotic in vivo and the anti-biotic works,” he says. “It’s resistant in the Petri dish, but it’s working in the animal. So is it the animal’s ability to metabolize that antibiotic and get it to the area that needs to be addressed?”