I have now posted quite a few times about ways to reduce antibiotic use in the NICU, and in the term baby nursery.
One thing that would help to reduce unnecessary usage is to abandon the idea that culture-negative sepsis is an entity that needs to be treated with antibiotics. I well remember a pair of mono-chorionic twins from several years ago that had identical presentations of early-onset sepsis with shock in the first few hours of life. One had a blood culture positive for E. Coli, the other had negative cultures. Presumably the cytokine/inflammatory response in the bacteremic twin had been shared with his brother through anastomotic channels. Treating such an inflammatory response syndrome with antibiotics is unlikely to improve outcome.
A great perspectives article recently published on-line in Pediatrics (Cantey JB, Baird SD. Ending the Culture of Culture-Negative Sepsis in the Neonatal ICU. Pediatrics. 2017) reviews the reasoning many people use to continue antibiotics in the face of negative cultures. They note the following:
1. if a culture of at least 1 mL is obtained before starting antibiotics, the sensitivity of detecting organisms down to a bacterial density of 4 CFU/mL is close to 100%, and is probably even better with the newest culture techniques.
2. Infants with negative cultures at 36 to 48 hours who have their antibiotics stopped virtually never need further treatment.
3. Infants who have negative cultures after maternal antibiotic therapy were either not infected or have been adequately treated. This is not a reason for continuing antibiotics.
4. Ancillary tests (CRP, procalcitonin, and the like) are of no use for deciding if a baby is septic, they have poor positive predictive value, and are non-specific.
5. Our clinical opinion as to the likelihood of sepsis is very poorly predictive of true sepsis.
“Culture negative sepsis” may indeed exist, the example I gave above is one situation which you could call by that name, viral infections, leading to an inflammatory response, are another. Neither situation is likely to benefit from prolonged antibiotic therapy.
The authors conclude that we need to learn to trust our blood cultures
Put simply, if the bacteria cannot grow in the blood culture bottle (an ideal medium at an ideal temperature, free of antibiotics, complement, or phagocytes), then why would they grow effectively in the infant’s bloodstream? As we learn more about the adverse effects of antibiotic exposure on short- and long-term neonatal outcomes, it becomes increasingly clear that prolonged antibiotic therapy for suspected sepsis is a luxury our infants cannot afford.
If you have access, I urge you to read this well-reasoned and well-written piece, and take its message to heart. Prolonged antibiotic therapy in the face of negative cultures increases the risk of later sepsis, and of necrotizing enterocolitis. Killing probiotic organisms in the gut with antibiotics allows the overgrowth of pathogens which can then wreak havoc.
I think we should have a rule that antibiotics are always stopped after 36 hours. Continuing them would then need a definitive decision, which would be easy if the cultures are positive, and should almost always be a decision to not restart in the face of negative blood cultures.