Needle in the haystack, infectious pathway, take 6.
This is a retrospective study looking at early vs late diagnosis of bacterial meningitis from three hospitals in Denmark (one looking at data from 1998-2014; the other two from 2003-2014). To be eligible, patients had to be >15 years of age, and, obviously, had to be hospitalized with a clinical presentation consistent with possible community acquired meningitis (any combination of headache, neck stiffness, fever, altered mental status, petechiae) with no alternative diagnoses made during or after admission. Furthermore, all patients also had to have a proven bacterial etiology by either: positive CSF culture, positive blood culture and CSF with >10 wbcs, bacteria seen on CSF gram stain, or bacteria in CSF by PCR or antigen analysis.
So what is early and what is late diagnosis? They define “early diagnosis” as being recognized in the ED (1.3 hours to antibiotics median), and “late diagnosis” as, well, not diagnosed in the ED (ie, diagnosed on the wards- 13 hours to antibiotics median). Over roughly 15 years, they saw 358 cases of bacterial meningitis, (~8 cases per year per institute – seems a bit high? They do not mention total number of annual ED visits), with 32% being classified as diagnosed “late.” … so, probably 2-3 cases a year of “late” diagnosis – a true needle in the haystack.
Why the late diagnosis? They tended to be older (65 years of age vs 56), less likely presenting with headache (58% vs 82%), less likely with neck stiffness (36% vs 78%), less likely with fever (59% vs 78%), with the classic triage of AMS, fever, and neck stiffness was only present 20% of the time in the late diagnosis group vs 50% in the early diagnosis…. So, it wasn’t an easy catch.
Why does this matter? Welp, with early antibiotics having a positive effect on mortality (18% vs 36%) as well as unfavourable outcome (which they do not actually define, 37% vs 66%, in favor of early antibiotics). This is a HUGE difference in mortality and unfavourable outcomes if you do not catch it early! … Then again, do we do more harm by giving 1-2g of ceftriaxone to everyone who is a bit altered? Would the risk of cdiff then outweigh the 2-3 annual misses? I’m not so sure. What about the recurrent headaches and repeat visits for post-LP headaches?
If you really want to tease out the data a bit, 53% of late diagnosis patients vs 26% or earlier diagnosis patients had a head CT before the LP. 72% of “late diagnosis” patients tentatively had a non-infectious etiology- so let’s explore some of the tentative diagnoses:
loss of consciousness (19 patients)
stroke (12 patients)
intracranial / subarachnoid hemorrhage (7 patients)
impaired mental status (6 patients)
headache (5 patients)
back pain (5 patients)
seizures (5 patients)
loss of vision (2 patients)
What I’m seeing here is a a trend towards a neurologic issue (a CT scan, a diagnosis of syncope / seizures, AMS, etc) – which may indicate that the thought of meningitis (or even endocarditis) may not have been entertained. Cant make the diagnosis if you dont think about it. In a similar vein, this diagnosis is rare and runs across a spectrum – on one end, the febrile, meningeal and altered, on the other, the vaguely unwell. And that, surprisingly, even a 12 hour delay to antibiotics can wreck havoc on the patient.
The take home points? Be vigilant, entertain the spectrum of disease for meningitis, but remember that every decision you make has consequences, including the decision to, and not to, perform an LP, not to mention the decision to indiscriminately give antibiotics for those “altered”. Choose wisely, and remember there is no such thing as zero risk.