Why a common infection is forcing doctors to look closer at their lab reports.
By Science Insights • August 2023
Imagine you're a doctor in a hospital. A patient has a dangerous bloodstream infection. The lab identifies the culprit as Enterococcus faecalis, a common bacterium, and runs tests to see which antibiotics will kill it. The report comes back: the bug is "susceptible" to ampicillin, a workhorse antibiotic. It seems like an open-and-shut case. But what if that label was hiding a deadly secret?
Recent research is revealing a troubling scenario. A specific strain of E. faecalis that tests as susceptible to ampicillin in the lab can act like a much more formidable foe inside the human body, leading to worse outcomes for patients. This story isn't just about superbugs resistant to everything; it's about a subtle mismatch between lab tests and real-life treatment that is making a common infection more deadly than it needs to be. Let's dive into the science behind this medical mystery.
To understand the problem, we need to meet the key players.
This bacterium is a normal part of our gut flora, but it can turn into a dangerous pathogen if it enters the bloodstream—through a surgical wound, a urinary tract infection, or a central line. Bloodstream infections with E. faecalis are serious and carry a significant risk of death.
You've probably heard of penicillin, the first widely used antibiotic. Ampicillin is a closely related, synthetic version. For decades, doctors have used them almost interchangeably to treat E. faecalis. The crucial detail is this: all ampicillin is a type of penicillin, but not all penicillin is ampicillin.
In the laboratory, tests are done with specific, pure concentrations of each drug. A bug is labeled "susceptible" if it stops growing when exposed to a standard dose of the drug. However, some strains of E. faecalis have developed a clever trick: they produce enzymes called beta-lactamases that break down basic penicillin but are less effective against ampicillin. So, in the lab test, they appear "ampicillin-susceptible" but are, in fact, "penicillin-resistant."
The critical question became: If a lab report says "ampicillin-susceptible," does it matter if the bug is secretly resistant to plain penicillin? And if a doctor, following old guidelines or hospital protocols, prescribes penicillin instead of ampicillin, could the patient be in danger?
To answer this life-or-death question, a team of researchers designed a retrospective study. Instead of running new lab experiments, they looked back at real patient data to find patterns and connections.
The researchers followed a clear, logical process:
They sifted through hospital records to find all patients who had a bloodstream infection caused by E. faecalis over a several-year period.
Using saved bacteria samples from these patients, they used advanced lab techniques to identify which infections were caused by the specific strains that are Ampicillin-Susceptible but Penicillin-Resistant (AS-PR) versus strains that are susceptible to both drugs (AS-PS).
For each patient, they collected key information: what antibiotic they were initially treated with, their underlying health conditions, how long they stayed in the hospital, and—most critically—whether they died from the infection.
Using complex statistical models, they compared the outcomes between the two groups, carefully controlling for other factors that could influence survival (like age or cancer), to isolate the true effect of the bacterial strain and the treatment choice.
The results were striking. Patients infected with the AS-PR strain had significantly worse outcomes, but there was a crucial twist: the choice of initial antibiotic therapy made all the difference.
The core finding was that the AS-PR strain was more virulent, but this increased danger was primarily realized when patients were treated with penicillin. When doctors used ampicillin from the start, outcomes were much better.
| Bacterial Strain | Initial Treatment | Mortality Rate | Clinical Cure Rate |
|---|---|---|---|
| AS-PR | Penicillin | 28% | 65% |
| AS-PR | Ampicillin | 12% | 88% |
| AS-PS (Susceptible to both) | Penicillin or Ampicillin | 14% | 86% |
This simplified data shows that patients with the AS-PR strain fared poorly when given penicillin, but almost as well as other patients when given the correct drug, ampicillin, from the start.
Why is this so important? It highlights a "treatment-bug mismatch." The lab report, by only highlighting ampicillin susceptibility, can mislead clinicians into thinking penicillin is a safe and equivalent choice. It is not. The AS-PR strain, while controlled by ampicillin, can survive and cause more harm when faced with the weaker penicillin.
| Strain Type | Lab Result for Penicillin | Lab Result for Ampicillin | Real-World Threat if Treated with Penicillin |
|---|---|---|---|
| AS-PS | Susceptible | Susceptible | Low |
| AS-PR | Resistant | Susceptible | High |
The problem lies in the discrepancy. The "Susceptible" result for ampicillin can obscure the "Resistant" result for penicillin, creating a blind spot for prescribers.
| Scenario | Average Hospital Stay | Risk of Complications |
|---|---|---|
| Correct antibiotic (Ampicillin) from Day 1 | 10 days | Low |
| Started on Penicillin, switched to Ampicillin later | 16 days | High |
Every hour spent on an ineffective antibiotic gives the infection a chance to strengthen and spread, leading to longer, more complicated, and more expensive hospital stays.
How do researchers and labs identify and study these tricky bacteria? Here's a look at some of the essential tools.
A lab staple. These plastic strips have a gradient of antibiotic on them. They are placed on a bacteria-covered plate; the point where growth stops shows the Minimum Inhibitory Concentration (MIC)—the lowest dose that stops the bug. This is how "susceptible" vs. "resistant" is determined.
A specific chemical test that acts as a litmus test for the bacterial enzyme that destroys penicillin. A color change confirms the presence of the resistance mechanism.
The genetic detective. These chemicals are used to amplify and detect the specific gene (blaZ) that instructs the bacterium to produce the penicillin-destroying beta-lactamase enzyme. This is the gold standard for confirmation.
The starting point. A special nutrient-rich liquid in a bottle into which a patient's blood sample is injected. If bacteria are present in the blood, they will grow in this media, alerting the lab to an infection.
The story of AS-PR Enterococcus faecalis is a powerful reminder that medicine is not always black and white. A "susceptible" label in the lab does not always tell the whole story. This research urges an important shift in clinical practice:
By connecting precise laboratory science with real-world patient outcomes, this research provides a clear path forward: look closer, question assumptions, and tailor treatments with an extra layer of caution. In the fight against infection, the smallest detail can make the biggest difference.