Category: Infectious Disease

Less is More, Cellulitis Edition

Generally speaking, the diagnosis of cellulitis is a fairly straightforward clinical evaluation – even in the Emergency Department. This article, however, says “we’re doing it wrong!” to the tune of $225M of waste on the inpatient side.

These authors retrospectively reviewed 183 patients admitted through their hospital system for a diagnosis of cellulitis, with a focus on imaging and blood cultures obtained. Of these, 83 (45%) underwent at least one form of imaging, with a handful a greater number, with 8 identifying an important additional or alternative diagnosis. Then, 60 (33%) received blood cultures, one of whom had conclusive culture growth – although the authors do not characterize whether it changed or narrowed antibiotic therapy. They ultimately conclude, in these otherwise non-toxic patients, these tests are of low value and ought be severely curtailed.

As much as I generally agree with the various Less is More-themed articles in this vein, I’m not sure this one entirely hits the mark. These 183 patients are inpatient hospitalizations, with progressive disease or significant comorbid disease – a far cry from the uncomplicated cellulitis representing the majority of our throughput. While these statistics may look grim, and they absolutely reflect generally low-value practice, this is a heterogenous cohort of patients in whom some of these tests were reasonable based on clinical examination and a reasonable pretest likelihood of a clinical important alternative entity. There is prudence and value to be found in reflecting on the assessment of cellulitis – but $225M might be a little bit of hyperbole.

“Clinical Usefulness of Imaging and Blood Cultures in Cellulitis Evaluation”

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2676998

Metronidazole is Out for C. Diff

Time to update USMLE, ABEM, ABIM, and every other standardized test given in medicine – the old standby, metronidazole, has been downgraded for the treatment of Clostridium difficile infection.

This update from the Infectious Disease Society of America, published last month, refreshes clinical practice guidelines for C. diff. The article covers a few different topics, including the population to be tested, the criteria for diagnosis, and a whole host of management and prevention factors. As with any comprehensive guideline, there is the occasional discordance between the strength of the recommendation and the quality of the underlying evidence, so the generalizability of their recommendations may have limitations.

However, tucked into all the various nuances (which are all mostly worth looking over, of course), is one of the most profound changes – metronidazole has been demoted from first-line for C. diff infection. The co-first line agents are now oral vancomycin or oral fidaxomicin. The authors effectively cite the continued use of metronidazole as anachronistic dogma, with vancomycin repeatedly demonstrated as having greater effectiveness. Cure rates with oral vancomycin range from 80-97%, while metronidazole is a rung down at 70-84%. Unfortunately, the cost of oral vancomycin and fidaxomicin remains highly burdensome – leaving a role for metronidazole, but not preferred as before.

It should be noted virtually every author of the guideline has some sort of relationship with a pharmaceutical company, including the manufacturer of fidaxomicin.  That said, oral vancomycin is generic – if still expensive – and has been around a long time.

“Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)”
http://www.idsociety.org/Guidelines/Patient_Care/IDSA_Practice_Guidelines/Infections_By_Organ_System-81567/Gastrointestinal/Clostridium_difficile/

The qSOFA Story So Far

What do you do when another authorship group performs the exact same meta-analysis and systematic review you’ve been working on – and publishes first? Well, there really isn’t much choice – applaud their great work and learn from the experience.

This is primarily an evaluation of the quick Sequential Organ Failure Assessment, with a little of the old Systemic Inflammatory Response Syndrome thrown in for contextual comparison. These studies included those in the Intensive Care Unit, hospital wards, and Emergency Departments. Their primary outcome was mortality, reported in these studies mostly as in-hospital mortality, but also 28-day and 30-day mortality.

The quick synopsis of their results, pooling 38 studies and 383,333 patients, mostly from retrospective studies, and mostly from ICU cohorts:

  • qSOFA is not terribly sensitive, particularly in the settings in which it is most relevant. Their reported overall sensitivity of 60.8% is inflated by its performance in ICU patients, and in ED patients sensitivity is only 46.7%.
  • Specificity is OK, at 72.0% overall and 81.3% in the ED. However, the incidence of mortality from sepsis is usually low enough in a general ED population the positive predictive value will be fairly weak.
  • In their comparative cohort for SIRS, which is frankly probably irrelevant because SIRS is already well-described, the expected results of higher sensitivity and lower specificity were observed.

Their general conclusion, to which I generally agree, is qSOFA is not an appropriate general screening tool. They did not add much from a further editorial standpoint – so, rather than let our own draft manuscript for this same meta-analysis and systematic review languish unseen, here is an abridged version of the Discussion section of our manuscript written by myself, Rory Spiegel, and Jeremy Faust:

This analysis demonstrates qualitatively similar findings as those observed in the original derivation study performed by Seymour et al. We find our pooled AUC, however, to be lower than the 0.81 reported in their derivation and validation cohort, as well as the 0.78 reported in two external validation cohorts. The meaning of this difference is difficult to interpret, as the clinical utility of this instrument is derived from its use as a binary cut-off, rather than an ordinal AUC. Our sensitivity and specificity from our primary analysis, respectively, compare favorably to their reported 55% and 84%. We also found qSOFA’s predictive capabilities remained robust when exposed to our sensitivity analyses. When only studies at low risk for bias were included, qSOFA’s performance improved.

While our evaluation of SIRS is limited by restricting the comparison solely to those studies which contemporaneously reported qSOFA, our results are broadly consistent with results previously reported. The SIRS criteria at the commonly used cut-off benefits from superior sensitivity for mortality in those with suspected infection, while its specificity is clearly lacking due to its impaired capability to distinguish between clinically important immune system dysregulation and normal host responses to physiologic stress. The important discussion, therefore, is whether and how to incorporate each of these tools – and others, such as the Modified Early Warning Score or National Early Warning Score – into clinical practice, guidelines, and quality measures.

The current approach to sepsis revolves around the perceived significant morbidity and mortality associated with under-recognized sepsis, favoring screening tools whose purpose is minimizing missed diagnoses. Current sepsis algorithms typically rely upon SIRS, depending on its maximal catchment at the expense of over-triage. Such maximal catchment almost certainly represents a low-value approach to sepsis, considering the in-hospital mortality of patients in our cohort with ≥2 SIRS criteria is not meaningfully different than the overall mortality of the entire cohort. The subsequent fundamental question, however, is whether qSOFA and its role in the new sepsis definitions provides a structure for improvement.

Using qSOFA as designed with its cut-off of ≥2, it should be clear its sensitivity does not support its use as an early screening tool, despite its simplicity and exclusion of laboratory measures. However, in a cohort with suspected infection and some physiologic manifestations of sepsis, e.g., SIRS, the true value of qSOFA may be in prioritizing a subgroup for early clinical evaluation. In a healthcare system with unlimited resources, it may be feasible to give each patient uncompromising evaluation and care. Absent that, we must hew towards an idealized approach, where our resources are directed towards those highest-yield patients for whom time-sensitive interventions modify downstream outcomes.

Less discussed are the direct, patient-oriented harms resulting from falsely-positive screening tools and over-enrollment into sepsis bundles. Recent data suggests benefits from shorter time-to-antibiotics administration intervals are realized primarily in critically ill patients. As such, utilization of overly sensitive tools, such as the SIRS criteria, would lead to over-triage and over-treatment, leading to potential iatrogenic harms in excess of net benefits. These harms include effects on individual and community patterns of antibiotic resistance, as exposure to broad-spectrum antibiotics leads to induction of extended-spectrum beta-lactamase resistance in gram-negative pathogens or vancomycin- and carbapenem-resistance in enterococci. Unnecessary antibiotic exposures lead to excess cases of C. difficile infections. The aggressive fluid resuscitation mandated by sepsis bundles leads to metabolic derangement and potential respiratory impairment. Further research should assess the extent of these harms, and in what measure they counterbalance those benefiting from time-sensitive interventions.

This meta-analysis has several limitations. First, we were limited by the relative dearth of high quality prospective data; most of the studies included in our analysis were retrospective. Second, we restricted our prognostic analyses to mortality alone, rather than diagnosis of sepsis. We chose to analyze only mortality because of competing sepsis definitions among expert bodies and government-issued guidelines. Among them, however, mortality is a common feature, the most objective metric, and manifestly the most important patient-centered outcome. Our analysis would not capture other important sequelae of sepsis, including amputation, loss of neurologic and/or independent function, chronic pain, and prolonged psychiatric effects of substantial critical illness. Third, we do not know whether patients included in these studies were septic on presentation, or developed sepsis later in their hospitalization. This may degrade the accuracy assessment of both SIRS and qSOFA. Fourth, while we know that qSOFA alone may miss some cases of sepsis that SIRS might detect, we do not know how many would, in reality, have been deprived of antibiotics and other necessary treatments. In other words, the fate of “qSOFA negative” patients who were evaluated and treated by physicians qualified to detect and treat critical illness via clinical acumen is not known; nor it should not be presumed that all such patients would have necessarily been deprived of timely treatment. Our analysis and comparison of SIRS is definitively incomplete, and not the most reliable estimate of its diagnostic characteristics, but provided for incidental comparison.

The prudent clinical role for qSOFA, however, is as yet undefined, and these data do not offer insight regarding its superiority to clinician judgment for determining a cohort at greatest risk for poor outcomes. Compared with SIRS, at least, those patients identified by qSOFA likely better represent the subset of patients for whom aggressive early treatment confers a particular advantage, and may drive high-value care in the sepsis arena. Future research should assist clinicians in further individualizing initial treatment of sepsis for those stratified to differing levels of risk for poor outcome, as well as to account for the iatrogenic harms and system costs.

“Prognostic Accuracy of the Quick Sequential Organ Failure Assessment
for Mortality in Patients With Suspected Infection: A Systematic Review and Meta-analysis”
http://annals.org/aim/fullarticle/2671919/prognostic-accuracy-quick-sequential-organ-failure-assessment-mortality-patients-suspected

Is the Urinalysis Reliable in Young Infants?

The evaluation of the very young infant with a fever is complex, with multiple competing factors including the rarity of serious illness, the severity of serious illness, and the cost of the intensive evaluation frequently required. The most commonly identified bacterial source for fever is a urinary tract infection, and our bedside test in the Emergency Department is the urinalysis.

So, how reliable and accurate is that test?

This is an analysis of prospectively collected data from the PECARN network, looking at the evaluation of febrile infants fewer than 60 days of age. Of 4,147 patients enrolled, 289 patients had UTIs by a 50,000 CFUs/mL definition on the subsequent urine culture. Only 27 patients had bacteremia and a UTI. The news is generally mixed: using the 50,000 CFUs/mL cut-off, any abnormality on the UA was 94% sensitive for UTI and 91% specific, but was 100% sensitive for a UTI associated with bacteremia.

The authors also do analyses including different cut-offs for UTI based down to 10,000 CFUs/mL and, as you might expect, the sensitivity for any UTI diminishes. While the interpretation of the urine culture result is less applicable to the initial Emergency Department evaluation, the subsequent threshold for diagnosis is relevant to the ongoing follow-up care for the febrile infant, particularly if an initial decision involved observation without antibiotics and the infant remains symptomatic without another source.

Overall, it is reasonable to suggest – if the UA is negative, a serious bacterial illness is unlikely to be present. Some consideration should be made to the duration of illness, and natural course of delayed onset of development of cystitis or pyuria in the urine. A positive UA, however, despite the apparent high specificity, does not reliably indicate a true positive for UTI, owing to the low prevalence. This should also be taken into consideration regarding whether additional invasive evaluation is indicated.

“Accuracy of the Urinalysis for Urinary Tract Infections in Febrile Infants 60 Days and Younger”
http://pediatrics.aappublications.org/content/early/2018/01/12/peds.2017-3068

The HSV Meningitis Question

This is one of those questions that always crops up when evaluating an infant for sepsis and meningitis – should we test and/or empirically cover for herpes simplex virus infection? Just how frequently is this diagnosis made?

The answers, as described in this retrospective, multi-center study, are complex. First, the basics: 26,533 total encounters analyzed, with 112 children ultimately diagnosed with HSV meningitis. Then, it’s basically chaos. The percent of patients whose CSF was tested for HSV ranged from 12.5% to 70.9% across hospitals included, along with empiric coverage with acyclovir ranging from 4.2% to 53.0%. Rates of positive HSV results were unrelated to overall institutional testing or empiric acyclovir coverage rates, excepting in the sense that HSV infection was more frequent in younger infants – and younger infants were more likely to be tested and empirically treated, in general.  A handful of patients with ultimate diagnoses of HSV meningitis were not treated or tested initially, and were found on a subsequent visit.

The authors go into some detail regarding the questionable value of empiric treatment, citing a number needed to treat of 152 for infants 0-28 days and an NNT of 583 for infants from 29-60 days. Generally speaking, these authors agree with a prior cost-effectiveness analysis recommending waiting for the initial CSF cell count, and empirically treating those with a CSF pleocytosis. Consequently, these authors would therefore recommend testing only those ultimately treated empirically – but this is naturally a pragmatic consideration, rather than a statistically modeled balance between sensitivity and specificity.

There are a few more nuances within the paper with regard to their gold standard for diagnosis of HSV meningitis, limitations with regard to selection of patients undergoing testing, and generalizability from these tertiary referral settings, but it is still generally an interesting snapshot of data. Unfortunately, their ultimate conclusion is still back at square one – reiterating a call for specific clinical and laboratory data to help guide clinicians in selecting patients for HSV testing and empiric treatment. In the meantime, we’ll just keep doing our best to differentiate the ill child at the bedside based on gestalt and the culture of our practice setting.

“Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation”
http://pediatrics.aappublications.org/content/early/2017/12/29/peds.2017-1688

Influenza, Sideways

Hello, everyone! Influenza, influenza, influenza. Influenza? Influenza. Influenza influenza, influenza – influenza – influenza, influenza!

It’s that time of year in the Northern Hemisphere, following up last year’s busy season, and a terrible one in the Southern Hemisphere in the interim. At this point, for your general ambulatory patient, I hope you’ve stopped sending swabs. If you think they have it, they probably do – although, there is some respiratory syncytial virus out there, too.

But, I’ve also been surprised by a couple of people who didn’t look like typical influenza, and this little expert commentary is a nice reminder of the less-common manifestations of influenza infection. The respiratory compromise is well-documented, but patients can not uncommonly become seriously ill with myocarditis, myositis, and viral encephalitis, as well as causing less serious serious hepatic injury and acute tubular necrosis. There have also been case reports implicating influenza less frequently in a scattershot of clinically interesting entities.

Just in case you weren’t getting enough influenza in your life.

“The hidden burden of influenza: A review of the extra- pulmonary complications of influenza infection”
http://onlinelibrary.wiley.com/doi/10.1111/irv.12470/abstract [open access]

Treatment Failure, or is Treatment the Failure?

Acute respiratory tract infections – otitis media, streptococcal pharyngitis, and sinusitis – comprise virtually a laundry list for antibiotic overuse in self-limited conditions. Certainly, a subset of each of these conditions are true bacterial infections and, again, a subset of these have their resolution hastened by antibiotics – and, finally, a subset of those would have clinically important worsening if antibiotics were not used. Conversely, the harms of antibiotics are generally well-recognized,though not necessarily routinely appreciated in clinical practice.

This patient-centered outcomes study, with both retrospective and prospective portions, enrolled children diagnosed with the aforementioned “acute respiratory tract infections” and evaluated outcomes differences between those receiving “narrow-spectrum” antibiotics and those receiving “broad-spectrum antibiotics”. Before even delving into their results, let’s go straight to this quote from the limitations:

Because children were identified based on clinician diagnosis plus an antibiotic prescription to identify bacterial acute respiratory tract infections, some children likely had viral infections.

“Some children likely had viral infections” is a strong contender for understatement of the year.

So, with untold numbers of viral infections included, it should be no surprise these authors found no difference in “treatment failure” between narrow-spectrum and broad-spectrum antibiotics. Nor, in their prospective portion, did they identify any statistically difference in surrogates for wellness, such as missed school, symptom resolution, or pediatric quality of life. However, adverse events were higher (35.6% vs. 25.1%, p < 0.001) in the broad-spectrum antibiotic cohort, and this accompanied smaller, but consistent, differences favoring narrow-spectrum antibiotics on those wellness measures.

So, the takeaway: broad-spectrum antibiotics conferred no advantage, only harms. If you’re using antibiotics (unnecessarily), use the cheapest, most benign ones possible.

“Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections”

https://jamanetwork.com/journals/jama/article-abstract/2666503

The Best Antibiotic Stewardship Money Can Buy

Believe it, or not:

Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance.

So, should we all be jumping on the procalcitonin bandwagon? Chances are, you probably already have – check with your critical care team, and I expect you’ll find some implementation of a procalcitonin-based protocol supporting antibiotic stewardship. The underlying concept is hardly unreasonable – when sensitive markers of bacterial infection are low, antibiotics can be discontinued.

However, the evidence base – as helpfully pooled in this individual-patient meta-analysis – is nothing more than a carefully orchestrated disinformation campaign by the manufacturers of these assays. Roche, Thermo-Fisher and bioMérieux have an obvious vested business interest in publishing favorable research findings in support of procalcitonin-based treatment algorithms, and it should come as no surprise the authors have a couple items to declare:

PS, MC-C, and BM have received support from Thermo-Fisher and bioMérieux to attend meetings and fulfilled speaking engagements. BM has served as a consultant for and received research support from Thermo-Fisher. HCB and MB have received research support from Thermo-Fisher for a previous meta-analysis regarding procalcitonin. DWdL’s hospital received financial support for the randomisation tool by ThermoFisher. DS, OB, and MT have received research support from Thermo-Fisher. TW and SS have received lecture fees and research support from Thermo-Fisher. CEL has received lecture fees from Brahms and Merck Sharp & Dohme-Chibret. JC has received consulting and lecture fees from P zer, Brahms, Wyeth, Johnson & Johnson, Nektar-Bayer, and Arpida. MW has received consulting and lectures fees from Merck Sharp & Dohme-Chibret, Janssen Cilag, Gilead, Astellas, Sano , and Thermo-Fisher. FT’s institution received funds from Brahms. CC has received an unrestricted grant of €2000 from Thermo-Fisher Scientific, and non-fiancial support from bioMérieux for the ProToCOLD study. YS has received unrestricted research grants from Thermo-Fisher, bioMérieux, Orion Pharma, and Pfizer. ARF has served on advisory boards for Novavax, Hologic, Gilead, and MedImmune; and has received research funding from AstraZeneca, Sanofi Pasteur, GlaxoSmithKline, and ADMA Biologics. J-USJ declares that he was invited to the European Respiratory Society meeting 2016 by Roche Pharmaceuticals.

And, it’s clearly no coincidence most of the 26 trials included in this systematic review are authored by those same financially-supported authors above – so, it’s turtles all the way down for this meta-analysis.

The results, then, for what they’re worth, despite all the concerted effort to spin them, are rather bland. The mortality differences are zero in the outpatient settings, and small enough in the intensive care unit side to potentially be skewed by design. The only signal I might ascribe reliable in these data is: procalcitonin does reduce antibiotic exposures. This manifests in practice in two different fashions, depending on the setting. In the outpatient setting, where virtually all the antibiotics are unnecessary (one of these trials enrolled patients with “bronchitis”!), it gives the clinicians a crutch to fall back upon to prevent them from practicing bad medicine.  In the intensive care unit, it helps titrate the use of broad-spectrum intravenous antibiotics, which is likely to reduce a number of important downstream effects.  I don’t object to the latter application, but my recommendation for the former: just don’t practice bad medicine in the first place (easier said than done, sadly).

So, the takeaway I’d like to promote in the context of this article – and its simultaneously published Cochrane Review by the same, COI-infested authors – is skepticism regarding the effect sizes for procalcitonin-guided therapy. These data do not exclude its clinical utility for the stated purposes, but its use ought be considered in the narrowest of clinical situations, and probably in those at the highest-risk for harms from otherwise clinically confounded antibiotic exposures.

“Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis”
https://www.ncbi.nlm.nih.gov/pubmed/29037960

Also, if you’re persistent enough to scroll to page 126 in the Cochrane Review full text, you glean this lovely pearl:
Philipp Schuetz received support (paid to his employer) from Thermo Fisher, Roche Diagnostics, Abbott and bioMerieux to attend meetings and fulfil speaking engagements. These conflicts breach Cochrane’s Commercial Sponsorship Policy (Clause 3), therefore Philipp Schuetz will step down as lead author at the next update of the review. Dr Schuetz’s declared conflicts were referred to the Funding Arbiter Panel and Cochrane’s Deputy Editor-in-Chief who have agreed this course of action but as an exception which does not set a precedent for similar situations in the future.

Alas, Abscesses [heart] Antibiotics

“Fake news!” All you need for effective treatment for abscesses is an incision and drainage procedure – adjunctive antibiotics are just unnecessary exposures with only marginal benefit, at best.

Then, unfortunately, two trials have been published in the New England Journal of Medicine showing benefit for antibiotics – either trimethoprim-sulfamethoxazole or clindamycin – improve the rate of clinical cure. The magnitude of benefit was somewhere in the range of a number needed to treat between 7 and 14, with infrequent harms, suggesting the balance of benefit may favor antibiotics. However, the abscesses included in these study tended to be large, suggesting perhaps these results weren’t easily generalizable.

This is a subgroup analysis of one of these two studies, trying to dredge out a specific population for whom antibiotics weren’t actually of value. And, unfortunately, for the purists among us, the results are bleak. Accounting for the diminishing statistical power and reliability of such an analysis, there are few useful signals within these data. Neither the size of the abscess nor the area of surrounding erythema reliably predicted diminishing returns from adjunctive antibiotics, nor did presence of fever or comorbid illness. The only probably reliable signal in these data, consistent with results in the era prior to MRSA, shows antibiotics are probably unnecessary for those who are not infected with staphylococci. Unfortunately, until that point where the causative agent can be easily ascertained at the time of I&D procedure, these data aren’t terribly useful in a practical sense.

So, the benefit is not universal, but it’s nothing at which to scoff. Perhaps a delayed antibiotic strategy could be considered, but, it seems most patients ought be offered antibiotics following drainage of a clinically significant abscess.

“Subgroup Analysis of Antibiotic Treatment for Skin Abscesses”
http://www.annemergmed.com/article/S0196-0644(17)31383-5/abstract

CT (Almost) Never Before LP

The guidelines describing the patients with suspected bacterial meningitis for whom neuroimaging is indicated prior to lumbar puncture are quite broad. The Infectious Disease Society of America includes virtually every imaginable mental status or immune system impairment, and guidelines in Europe are similar. The anachronistic concern: cerebral herniation in the setting of increased intracranial pressure leading to an otherwise potentially avoidable death. But, guidelines in Sweden are different. In Sweden, their neuroimaging guidelines suggest only those virtually comatose or with focal neurologic signs should undergo CT prior to LP.

In this review of patients with acute bacterial meningitis from a Swedish registry, the authors attempt to parse out whether a decision to perform CT is not only unnecessary – but also potentially harmful. They analyze 815 patients ultimately diagnosed with bacterial meningitis and stratify them by those who received LP without CT, LP before CT, and CT before LP. Presenting features and comorbid medical conditions were abstracted retrospectively, and the results were analyzed with respect to the varying guideline recommendations, mortality, and functional outcomes.

The clear winner: CT rarely before LP, as in Sweden. By their guidelines, only ~7% of those ultimately diagnosed with bacterial meningitis had indication for CT prior to LP – but, unfortunately, 52% of patients underwent imaging anyway. The reason for “winning” if adherent to the Swedish strategy, however, was not just reduced resource utilization – it was mortality and functional outcomes. Mortality was almost halved in those for whom Swedish guidelines were followed, only rarely CT prior to LP. The authors attribute the signals for the underlying mortality difference to a greater percentage of patients receiving antibiotics within 1 hour or 2 hours when no CT was performed.

This probably overstates the magnitude of harm relating to CT use, as delays in antibiotics are probably more accurately delays in diagnosis, rather than logistics impacting timely delivery of antibiotics. After all, even in those with LP prior to CT, only 41% received steroids plus adequate antibiotics, so I expect the magnitude of effect seen here likely ties more reliably to confounding individual patient factors not easily adjusted for in a retrospective analysis.

That said, I do think the Swedes are doing the right thing – the vast majority of CTs were unhelpful. Their guidelines for neuroimaging – deep coma and/or lateralizing neurologic signs – will probably pick up any relevant findings (like the subdural empyema in this series), and reduce waste while obviating any possible delays in care.

“Lumbar puncture performed promptly or after neuroimaging in adult bacterial meningitis: A prospective national cohort study evaluating different guidelines”
https://academic.oup.com/cid/article-abstract/doi/10.1093/cid/cix806/4110207/Lumbar-puncture-performed-promptly-or-after