Tetanus review in Lancet ID

 A recent review of the topic appeared in Lancet Infectious Disease, linked here:

Tetanus: recognition and management

General

Tetanus is rare in the developed world but worth discussing because it is a must not miss diagnosis.

Tetanus is caused by infection with Clostridium tetani. It produces a neurotoxin that is transported to the CNS retrogradely (by reverse axonal transport) where it blocks inhibitory neurotransmitter release thereby allowing unopposed motor activity. Four forms of tetanus are described: neonatal (not discussed here), localized (near the site of injury), cephalic (localized to the head and neck ), and generalized. Either of the localized forms can progress to generalized tetanus.

Epidemiology

Although considered rare in the developed world, 17 to 33 cases are diagnosed yearly in the United States. Inoculation sources can include any violation of skin integrity. Injection drug use, any type of wound, piercings, acupuncture, subQ or IM injections (either therapeutic or recreational), are possible sources. Up to 30% of cases are associated with no discernible history of a wound or injury.  This epidemiology argues strongly for universal vaccination.

Clinical features

Clinical features include rigidity, spasm, trismus,  opisthotonus, and dysphagia. Fever is often present but not invariably at presentation.

Diagnosis

Diagnosis is based on clinical features and confirmatory testing. A high index of suspicion is important due to non-textbook presentations (acute abdomen, dysphagia, stroke concerns, dystonia).  The diagnostic test of choice is C tetani PCR from wound material. Anti tetanus toxin antibodies are also recommended, and while a low tighter is supportive of the diagnosis and high antibody levels rule against the diagnosis, this test is not definitive.  Occasional cases have been reported in patients who had “protective” antibody titers. 

Aspects of immunity

Natural infection does not confer immunity. Near elimination of the disease in the developed world is attributable to universal vaccination practices. Since there is no person to person transmission, herd immunity does not exist.

Treatment

Surgical debridement even for innocuous appearing wounds is indicated. Antibiotics should include metronidazole which according to low level evidence is associated with better overall outcomes. Antioxin in the form of tetanus immunoglobulin is indicated. Invasive mechanical ventilation is necessary in around 50% of patients and should this be required, primary tracheostomy is preferred. 

Benzodiazepines are an important part of the treatment with diazepam as the benzo of choice. High doses and continuous drips are often necessary. Adjunctive neuromuscular blockade may be needed.

Dysautonomia

Dysautonomia is common and is a significant cause of mortality.

IV magnesium sulfate as a treatment for dysautonomia is associated with improved outcomes and a bolus/drip regimen is recommended, targeting serum levels of 2 to 4 mmole/L. Opiates have a significant role in the management of dysautonomia. Otherwise, vasoactive drugs as appropriate for the patient’s hemodynamic state may be indicated.

Finally, general symptomatic and supportive care to include fluids, nutritional support, stress ulcer prophylaxis, VTE prophylaxis along with skin and wound care are indicated. 

The patient with cirrhosis: poised to bleed or poised to clot?

It turns out to be a little of both. A number of reviews have addressed this. [1] [2] [3]  Here are some of the key points:

The old maxim that cirrhotic patients are auto-anticoagulated is a myth. Severe liver disease is associated with a delicate balance between bleeding and clotting. In general, cirrhosis tends to be a hypercoagulable state. The relative risk for VTE in such patients has been estimated at around 2.

 

What are the mechanisms for the hypercoagulability of liver disease?

In primary hemostasis, while platelet numbers are often decreased these platelets tend to be hyper-functional. This is due to low levels of ADAM TS 13, correspondingly increased levels of VW factor and multifactorial endothelial dysfunction.

In secondary hemostasis, reasons for hypercoagulability include decreased levels of liver dependent natural anticoagulants such as protein C, protein S, and antithrombin. Factor VIII (not synthesized in the liver) tends to be increased.

There is also impaired fibrinolysis with increased levels of PAI-1 and decreased levels of plasminogen.

What are the clinical implications?

Traditional hemostatic tests are generally used but are of limited reliability. There's been increasing interest in global hemostatic tests such as viscoelastic assays which are conceptually more valid but are not yet ready for translation into clinical practice.

For low risk procedures, prophylactic hemostatic products peri-procedure are generally not indicated.

Antithrombotic treatments should be given in accordance with standard clinical indications recognizing a potentially increased risk of bleeding.

DOACs can be used in many patients but certain published restrictions apply.

Special circumstances where warfarin is favored over DOACs

 When is warfarin favored over DOACs?

 Valvular atrial fibrillation. 

This term is becoming obsolete. For anticoagulation for stroke prevention in atrial fibrillation  DOACs are contraindicated and warfarin favored in severe rheumatic mitral stenosis and mechanical prosthetic valves.

Liver disease. 

If Child Pugh is C DOACs are not recommended. If B, apixaban and rivaroxaban can be used “with caution” (FDA labeling ).   Child Pugh calculator.

 Antiphospholipid syndrome. 

Warfarin is favored (Up to Date). 

Morbid obesity: 

DOAC is okay for BMI up to 40. Above 40 rivaroxaban and apixaban are acceptable but other DOACs should be avoided. 

History of gastrectomy or weight loss surgery: 

Warfarin preferred. This review summarizes the rationale and recommendations regarding morbid obesity and patients who have had weight loss surgery.

In addition, certain drug interactions with DOACs are category X thus prohibiting use.

ACC atrial fibrillation guidelines 2023

 A few key points from the 2023 atrial fibrillation guidelines American College of Cardiology

New classification: 

The old classification is maintained but it is encompassed in a broader classification outlining the stages of risk and /or the occurrence of atrial fibrillation. 

Stage 1:  at risk. This refers to the presence of risk factors such as obesity and hypertension. 

Stage 2: pre atrial fibrillation encompassing structural abnormalities such as LAE or warning arrhythmias such as  atrial ectopy.

Wiithin atrial fibrillation itself the traditional categories of paroxysmal persistent and permanent remain. Right above permanent atrial fibrillation is another designation referring to successful ablation. 

Flexibility is built into the CHA₂DS₂-VASc score for anticoagulation decisions. 

If the risk is intermediate there is considerable equipoise and shared decision making is advised. 

Increased preference for early rhythm control.

There is an increased emphasis on early rhythm control especially in patients with heart failure and reduced ejection fraction. Catheter ablation via pulmonary vein isolation now he has a class 1 indication particularly in patients with who present with heart failure and reduced ejection fraction at the time of the onset of atrial fibrillation detection.   Specifically:

Rhythm control recommended over rate control if decreased left ventricular function and persistent or high burden atrial fibrillation, class 1 

If atrial fibrillation is symptomatic, class 2a. 

Specific arrhythmias related to fibrillation have been defined. 

Atrial tachycardia is defined as a rate greater than or equal to 100, non sinus. Mechanisms can be automaticity, triggered or micro reentry  Atrial flutter. is considered any tachyarrhythmia  that involves macro re-entry. Typical flutter involves macro reentry that goes through the cavo tricuspid isthmus. All others are considered atypical.

Caffeine avoidance is noted not to be beneficial. 

The designation of valvular versus non-value or atrial fibrillation has become obsolete. 

The recommendation now is that for a mechanical prosthesis or severe rheumatic mitral stenosis warfarin is recommended.  DOACs are preferred for all other patients unless there are certain disease-related or pharmacokinetic contraindications. 

In cases of cryptogenic stroke there is a 2a recommendation for extended monitoring. The guidelines do not specify the duration of monitoring. 

For device detection of high rate episodes, (specifically pacemaker detection), stroke risk is believed to exist but believed to be less than that of clinical episodes. 

If a high rate episode is detected and lasts greater than or equal to 5 minutes it is almost always atrial fibrillation. For device detection of high rate episodes lasting greater than or equal to 24 hours systemic anticoagulation is given a 2a recommendation.   For the range of 5 minutes to 24 hours this same situation has a 2b recommendation. In both cases there is considered to be sufficient equipoise that shared decision making applies.

Atrial appendage occlusion devices such as the Watchman have a 2a recommendation if CHA₂DS₂-VASc  is greater than or equal to 2 and anticoagulation is contraindicated. 

For high bleeding risk but not a contraindication the device is given a 2b recommendation. 

There are some changes in systemic anticoagulation recommendations for varying degrees of kidney disease. 

Up to and including stage 3 systemic anticoagulation if otherwise recommended for atrial fibrillation has a class 1 recommendation. It drops to class 2a for stage 4 and to 2B if there is  esrg/hd. 

In atrial fibrillation with rheumatic valve disease or mechanical prosthesis for which vitamin K antagonist anticoagulation is recommended the CHA₂DS₂-VASc  score does not apply. 

The long-term rate control goal is an upper rate limit of 100-110 and has a 2a recommendation. 

Acute rate control

If EF is greater than 40, IV beta blocker or non-dihydropyridine calcium blocker, class 1.  Digoxin  if above ineffective or contraindicated class 2a. 

IV mag sulfate class 2a. It may be better than standard agents. Up to five grams is considered low dose. Occasionally one could use greater than or equal to 5 g.  The main use is adjunctive.

Amiodarone if others ineffective or contraindicated, class 2b.

AVN ablation indications

AV node ablation if rate control is refractory to medication and the patient is otherwise a candidate, 2a. This will be combined with pacing obviously and initial lower rate limit, to avoid malignant ventricular arrhythmia, should be set at 80 to 90 with plans to program down by monthly decrements of 10 until 60 is reached. 

 Stroke prevention associatied with cardioversion 

 If atrial fibrillation could have been going on greater than or equal to 48 hours 3 weeks of anticoagulation first or tee prior to cardioversion and anticoagulation for greater than or equal to 4 weeks afterwards. 

 Drugs to maintain sinus rhythm long-term. 

The guidelines are not very explicit about whether drugs should even be used in the first place. They merely say that such are “ reasonable “  for patients who are " not candidates for, or decline” ablation. Similarly those who prefer antiarrhythmic therapy to ablation are considered reasonable candidates. The implication is that you should probably do something to maintain sinus rhythm. 

If normal EF and no structural heart disease and no coronary disease then fleccanide or propofanone 2a

Dronedarone 2a if no recent decompensated HR and if HF class II or better.

Dofetilide 2a if no long QT or torsades risks and no hypokalemia or hypomag, or tendency thereto.

Amiodarone  is 2a but the agents above may be preferable. 

Sotalol is 2b with the same precautions that apply to dofetilide. 

In pts with prior MI, structural disease or EF less than or equal to 40% no recent decompensation or functional class III or worse, dronedarone is 2a.

When does antiarrhythmic therapy need to be administered in the hospital?  And for how long?

Dofetilide 3 d

Sotolol, admit to hospital but the guideline does not specify how long.

ICs:  Observe at least after the first dose.

PVI catheter ablation (pulmonary vein isolation ):

if antiarrhythmics not tolerated, contraindicated or not preferred, class 1.  For younger patients with no or few comorbidities class 1 as  first line even if the atrial fibrillation is paroxysmal. 

For atrial flutter, class 1 ( it would be implied that this is typical flutter ). For a new diagnosis of atrial fibrillation in heart failure with reduced ejection fraction both at the same time early rhythm control is class 1 and ablation is said to be “ beneficial when appropriate” class 1. 

Autonomic dysfunction as a cause of cardiovascular disease

 

This free full text review focuses on neurodegenerative synucleinopathies and briefly, in addition, touches on other disorders such as POTS, vasovagal syncope and inappropriate sinus tachycardia.

Synucleinopathies result from misfolded protein aggregates of α-synuclein. The normal function of α-synuclein in the nervous system is not well understood.

The synucleinopathies are parkinson disease, lewy body dementia, pure autonomic failure and multiple system atrophy. Any of these disorders can be accompanied by autonomic dysfunction.

Orthostatic hypotension, supine hypertension, or both may occur. All of the long-term consequences of hypertension may be associated with the supine hypertension seen in autonomic dysfunction. Use of a short acting antihypertensive administered at night is a suggested treatment strategy.

Nucleic acid testing for viral pathogens in community-acquired pneumonia

 

The American thoracic Society has published a guideline for this in the American Journal of Respiratory and Critical Care Medicine. These are soft recommendations based on low-level evidence.

The guideline does not address influenza or covid.  For influenza, the IDSA community-acquired pneumonia guidelines recommend influenza PCR testing during flu season (in preference to antigen testing ). The  guidelines did not address covid-19 as there was insufficient data at the time of the literature review.

The guideline calls for viral PCR panel testing in the following groups of patients: those with neutropenia, those undergoing active cancer therapy, those with a transplant history, those with advanced HIV,  those with a history of chronic immunosuppression including systemic corticosteroids, and those whose community-acquired pneumonia is classified as severe.

Criteria for severity overlap with some of those just mentioned and include the presence of septic shock or need for mechanical ventilation. Absent these two conditions three of the following minor criteria denote severity: impaired respiratory physiology in the form of either a respiratory rate greater than 30 or a PO2 to Fio2 ratio below 250, multilobar infiltrates, altered mental status, BUN greater than 20, white blood cell count less than 4,000, platelet count less than 100,000,  hypothermia less than 36.8 centigrade or hypotension requiring aggressive fluid resuscitation.

Could aspergillus be hiding out in your critically ill patient?

 

An issue from the American Journal of respiratory and Critical Care Medicine contains two articles and a related an editorial addressing this subject.

This study looked for evidence of aspergillus infection in patients diagnosed with VAP:

Rationale: Aspergillus infection in patients with suspected ventilator-associated pneumonia remains uncharacterized because of the absence of a disease definition and limited access to sensitive diagnostic tests.

Objectives: To estimate the prevalence and outcomes of Aspergillus infection in adults with suspected ventilator-associated pneumonia.

Methods: Two prospective UK studies recruited 360 critically ill adults with new or worsening alveolar shadowing on chest X-ray and clinical/hematological parameters supporting suspected ventilator-associated pneumonia. Stored serum and BAL fluid were available from 194 nonneutropenic patients and underwent mycological testing. Patients were categorized as having probable Aspergillus infection using a definition comprising clinical, radiological, and mycological criteria. Mycological criteria included positive histology or microscopy, positive BAL fluid culture, galactomannan optical index of 1 or more in BAL fluid or 0.5 or more in serum.

Measurements and Main Results: Of 194 patients evaluated, 24 met the definition of probable Aspergillus infection, giving an estimated prevalence of 12.4% (95% confidence interval, 8.1–17.8). All 24 patients had positive galactomannan in serum (n = 4), BAL fluid (n = 16), or both (n = 4); three patients cultured Aspergillus sp. in BAL fluid. Patients with probable Aspergillus infection had a significantly longer median duration of critical care stay (25.5 vs. 15.5 d, P = 0.02). ICU mortality was numerically higher in this group, although this was not statistically significant (33.3% vs. 22.8%; P = 0.23).

Conclusions: The estimated prevalence for probable Aspergillus infection in this geographically dispersed multicenter UK cohort indicates that this condition should be considered when investigating patients with suspected ventilator-associated pneumonia, including patient groups not previously recognized to be at high risk of aspergillosis.

Another study in the same issue looked at the prevalence of aspergillus in patients on mechanical ventilation with covid-19. They found it in over 20% of patients.

The accompanying editorial cited additional evidence all of which suggests that aspergillus infection is under-diagnosed in critically ill patients.

Patients need not be immunosuppressed in the traditional sense although the use of corticosteroids, even short-term, is a major risk factor. The main use of corticosteroids  was for treatment of COPD exacerbations.

Antimicrobial resistance in critically ill patients

 

This review focuses mainly on gram-negative bacteria. Although it approaches the problem in light of the covid-19 pandemic it has general applicability.

First a few definitions.

ESKAPE microorganisms : Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp

Enterobacterales: new term for enterobacteriaceae

MDR: resistant to at least one antibiotic in three or more categories

XDR (extensive drug-resistant): resistant to at least one antibiotic in all but two or fewer categories

PDR (pan drug-resistant): resistant to all antibiotics

Difficult to treat resistant pathogens: resistant to front line agents and requiring second-line agents of greater toxicity and often lower efficacy (eg aminoglycosides, colistin).

Rates of infections due to ESBL producing organisms and carbapenemase producing organisms are rising. K. pneumoniae carbapenemase (KPC) producing bacteria are the ones predominant in the United States. The New Delhi Metallo-beta-lactamase (NDM) and the OXA-48 carbapenemase are rising in importance.

Acinetobacter is a complex and rising concern. From the review:

Finally,A. baumannii complex frequently causes nosocomial infections, particularly in ICUs where the incidence has increased over time. The SENTRY program evaluated the frequency of cases and anti-microbial susceptibility profiles of the A. baumannii collection from medical centers registered in this program [13]. This study showed that these isolates were recovered mainly from patients with pneumonia and bloodstream infections and evidenced reduced susceptibility to most antimicrobials tested. In all regions, colistin was the most active agent followed by minocycline.

Despite this seemingly grim picture the pipeline seems to have kept up with these trends reasonably well. Newer agents include:

Ceftolozane and tazobactam (Zerbaxa) Enhanced pseudomonas activity; activity against ESBL organisms but significant resistance rates; no activity against carbapenemase producing bacteria. (If used for intra abdominal infections coadministration of metronidazole is required).

Ceftazidime–avibactam (Avycaz) and imipenem–relebactam (Recarbrio) are active against most carbapenemase producing bacteria.

Not mentioned were fosfomycin (not yet available in IV form in the US) and omadacycline (Nuzyra). Omadacycline, though expected to be bacteriostatic, has an impressive spectrum. From another paper:

Omadacycline maintains activity against difficult-to-treat pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterobacteriaceae that produce extended-spectrum β-lactamases (ESBLs) and carbapenemases, and multidrug-resistant (resistant to greater than or equal to 3 classes of agents) strains of Acinetobacter spp. and Stenotrophomonas maltophilia (2).

ANCA testing in eosinophilic granulomatosis with polyangiitis (EGPA)

 

The American Journal of Respiratory and Critical Care Medicine published a consensus statement on the use of ANCA testing in patients with eosinophilic granulomatosis with polyangiitis  (EGPA,formerly Churg Strauss syndrome).  The article serves is a helpful update and review on some aspects of EGPA.

First some Basics about the ANCA test. The two main types have two different nomenclatures of designation depending on the assay used. In the ELISA test, which uses specific antigens, the two antibodies are proteinase three (pr3) and myeloperoxidase (MPO).  These correlate mainly (and there are some exceptions) with the immunofluorescent patterns of C and P ANCA respectively.

What about disease associations? Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) is generally associated with C ANCA. Microscopic polyangiitis (MPA) is generally associated with P ANCA. The same is true of pauci immune  renal limited vasculitis. These categories are not absolute.

When it comes to EGPA it's a little more complex. Only 40% or so of patients with EGPA are ANCA  positive and the predominant pattern is ANCA P.  Test characteristics of ANCA for GPA,  MPA and renal limited vasculitis are pretty good. This, as is evident from the above, is not the case for EGPA.

Now on to the paper.

Despite the poor test characteristics the consensus panel recommends testing on all patients or suspected EGPA patients because it may point to the correct diagnosis and has implications for disease phenotype. Here's the specific recommendation, from the abstract of the paper:

MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms; purpura; polyneuropathy; unexplained heart, gastrointestinal, or kidney disease; and/or pulmonary infiltrates or hemorrhage. A positive MPO-ANCA result contributes to the diagnostic workup for EGPA. Patients with MPO-ANCA–associated EGPA have vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations, more frequently than patients with ANCA-negative EGPA. However, the presence of MPO-ANCA is neither sensitive nor specific enough to identify whether a patient should be subclassified as having “vasculitic” or “eosinophilic” EGPA. At present, ANCA status cannot guide treatment decisions, that is, whether cyclophosphamide, rituximab, or mepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset.

According to the paper there are some important clinical correlations. EGPA patients who are anca positive tend more to have a vasculitic  manifestations such as glomerulonephritis, neuropathy, pulmonary Hemorrhage and skin lesions. Those who are negative tend more toward the infiltrative aspects of the disease which translates into cardiac involvement and pulmonary granulomas.

Treatment decisions are made more on clinical grounds than on the basis of the ANCA test. Again, from the paper:

Glucocorticoids  are  the  cornerstone  of  therapy  for  EGPA.  Additional  immunosuppressive agents  (e.g.,  cyclophosphamide)  should  be  prescribed  for  patients  with  life-  and/or  organ-threatening manifestations, such as heart disease, glomerulonephritis, alveolar hemorrhage or mononeuritis  multiplex,  and  can  be  considered  for  selected  patients  with  glucocorticoid dependence  or  recurrent  disease  [51].

Myths and facts in antibiotic stewardship

The current issue of the American Journal of Medicine (the Green Journal) has an article titled Top Myths of Diagnosis andManagement of Infectious Diseases in Hospital Medicine. This is one of the better articles pertaining to antibiotic stewardship that I have seen. Ten myths are listed. They are not complete myths (exceptions apply to just about all of these principles); rather, they are misconceptions.

Myth one: antibiotics do no harm. High-level data refute this myth. For example, a recent metaanalysis showed that the use of procalcitonin guidance to shorten the duration of antibiotic therapy was associated with lower mortality.

Myth two: antibiotic durations of 7, 14, or 21 days are typically necessary. Although these are common recommendations, evidence is lacking. In many situations (and there are exceptions) shorter duration therapy is as good as longer duration. Examples include 3 to 5 days for community acquired pneumonia; eight days for nosocomial pneumonia; 5 to 7 days for pyelonephritis; four days for intraabdominal infection; five days for acute exacerbations of COPD and 5 to 6 days for cellulitis. There are notable exceptions. Certain deep-seated and difficult to eradicate infections are not candidates for either shorter duration or procalcitonin guidance for discontinuation. These include tuberculosis, meningitis, prosthetic joint infections, staphylococcal bacteremia, endocarditis and invasive fungal infections. The same caution applies to some immunocompromised patients.

Myth three: if one drug is good two (or more!) must be better. This requires nuance.There are some indications for combination therapy. They are exceptions rather than the rule. The main indication for combination therapy is initial empiric treatment for life-threatening infection such as sepsis. The rationale is to cover all likely pathogens. De-escalation is appropriate if and when culture and sensitivity results indicate that a single agent would be appropriate. This principle is also applied in meningitis where in patients 50 years of age or older we include listeria coverage such that in non pen allergic patients ampicillin is added to the combination of ceftriaxone and vancomycin. Also in meningitis the combination of ceftriaxone and vancomycin accommodates the possibility of relative resistance of strep pneumo which might cause treatment failure with cephalosporin monotherapy. In community acquired pneumonia requiring hospitalizations the guidelines call for combination cephalosporin and macrolid therapy. For patients admitted to ICU it is recommended that MRSA coverage be added (this is in the IDSA MRSA guideline, not the pneumonia guidelines).

A frequently asked question is what to do about serious gram negative infections. Traditionally “double coverage“ with two gram-negative agents has been used. For the most part this is not supported by evidence. One exception is in the initial (empiric) antipseudomonal coverage for HAP/VAP., the guidelines for which indicate double coverage initially which should be de-escalated later if microbiologic data allow. In contrast, the CAP guidelines for patients with pseudomonas risk recommend monotherapy---not double coverage--from the start.

Myth four: oral antibiotics are not as good as IV antibiotics for hospitalized patients. This is, in general, a myth but there are exceptions. IV therapy is not inherently better than oral if there’s adequate bioavailability with the oral agent and if susceptibilities allow switch to an oral agent. Cautions apply in bacteremia. Some of these (eg staphylococcal bacteremia ) require intravenous therapy for the entire course. In other bacteremic infections step down to oral agents may be appropriate. Examples include certain streptococcal bacteremias and gram-negative bacteremic urinary tract infections. In such cases a switch to oral therapy can be considered as early as day four.

Myth five: bacteria in the urine signifies a UTI and should be treated. If it is asymptomatic treatment is only warranted in pregnancy and patients about to undergo a urologic procedure.

Myth six: history of penicillin allergy means the patient can never receive a beta lactam antibiotic. Former thinking was that there’s a 10 to 15% cross sensitivity rate between penicillin and cephalosporins. More recent findings indicate that the cross sensitivity rate to penicillin allergy is more like 3% for cephalosporins and 1% for carbapenems. The article provides some general principles for decision making in patients with purported penicillin allergy. For reactions that are mild and non specific a cephalosporin can be given. If the reaction was anaphylactoid either an alternative antibiotic to a cephalosporin or penicillin desensitization is recommended. Severe non anaphylactic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS syndrome are in a different category. In those cases the use of any beta lactam is contraindicated as is penicillin desensitization.

Myth seven: antibiotics for surgical prophylaxis should be continued for 24 hours or more .

Myth eight: antibiotics must be continued for as long as drains are in place. Although clinical judgment is required here there is no robust evidence to support such a practice.

Myth nine: nitrofurantoin can be used for UTIs only if the creatinine clearance is greater than 60. This is in accordance with product labeling but the data indicate 30 may be more reasonable cut off.

Myth ten: fluoroquinolones are first line agents for many infections. We now have mounting evidence of adverse effects (CNS toxicity,, tendon rupture, dysglycemias, irreversible neuropathy, QT prolongation and aortic dissection) such that fluoroquinolones have been relegated to a lower position in the sequence. They should be used only when safer and equally effective alternatives are not available.

In a related antibiotic stewardship topic this article from Cinical Infectious Disease looked at the utility of MRSA PCR screening. Negative PCR can allow for discontinuation or avoidance of MRSA therapy such as vancomycin in many situations. Those studied in the article were bloodstream infections, intra-abdominal infections, respiratory infections, wound infections and urinary tract infections. Negative predictive value was 93% or better in all those situations.

Diagnostic time out

What is a diagnostic time out? Succinctly defined, it’s a deliberate exercise in differential diagnosis and systematic clinical reasoning in the care of an individual patient. But wait, I hear someone say… isn’t that what we do already? Well, no. We’re all familiar with the traditional model for clinical reasoning that we’re taught in medical school but those of us in the real world of practice nowadays, if we’re honest, realize that it seldom happens. There’s just not enough time when you’re forced to see too many patients each day. And hospitalist incentives, with their emphasis on speed and quick adoption of specific diagnostic labels, run in opposition. What do we as hospitalists do instead? Well, aside from all the care pathways and metric incentives that tell us what to do, we rely on clinical instincts and rules of thumb. Because they bypass formal analysis, they save time. They serve as cognitive shortcuts. We call these heuristics. This method of thinking (fast, instinctive, intuitive) is sometimes known as system 1 thinking. It has the advantages of being efficient and fast and sometimes, in critical situations, life saving. But it comes at the cost of a certain error rate. In order to better understand the process of system 1 thinking we have given the various heuristics names and categories. I recently listed some of those in this post. 

If system 1 is our usual measure of processing to get around time constraints the alternative is system 2: formal clinical reasoning .  System 2 thinking was the topic of a recent paper in CriticalCare Clinics. Although based on a survey of people working in a NICU the article has general applicability. The authors contrast system 1 and system 2 thinking in this manner:

Dual process theory holds that individuals engaging in medical decision-making use one of 2 distinct cognitive processes: a system 1 process based on heuristics – the use of rapid pattern recognition and rules of thumb – or a system 2 process, based on deliberate analytical modeling and hypothesis generation. While invoking system one processes individuals can think fast and reflexively and can even operate at a subconscious level, using pattern recognition to sort vast amounts of clinical information quickly before an illness script that allows for the rapid elaboration of a differential diagnosis. In contrast system 2 processes require focused attention and are purposefully analytical, relying on deliberate counter-factual reasoning to generate hypotheses regarding the pathophysiologic mechanisms by which a patient’s symptoms are produced.

The authors introduced the concept of the diagnostic time out to describe this shift of thinking because it requires deliberate effort. It’s not going to arise spontaneously in the natural course of the ward routine. (The authors were not the first ones to use this term). The diagnostic time out can be considered the cognitive equivalent of the better known procedural time out.

Why is a diagnostic time out needed? Research on diagnostic error has indicated that while some instances are due to system problems (such as failure to communicate test results) most are cognitive errors. These can be linked to the heuristics of system 1 thinking. The diagnostic time out, or the deliberate exercise of system 2 thinking, is a way to complement these cognitive shortcuts with a more analytical process.

Some opinion leaders in the field of diagnostic error have suggested universal adoption of system 2 thinking. This is problematic due to time constraints. Besides, there are some essential benefits of system 1 thinking, particularly in acute life-threatening situations. The real trick is how best to selectively employ system 2 thinking. In other words what are the situations in which system 2 thinking should be used? The authors suggest handoff situations in complex patients including ER to hospitalist, off service/on service and ICU to ward transfers.

How does it work? The authors propose a template but it’s really just the traditional clinical reasoning process. One of their points really got my attention: during the time out diagnostic labels should be removed and replaced by signs, symptoms, manifestations and clinical concerns. This of course is the opposite of what your coders and hospitalist leaders want you to do.

What are some of the barriers to implementation? In addition to time constraints, fear of ambiguity is an important factor. We are afraid to admit what we don’t know. One thing you will never hear a hospitalist say out loud is “I’ll have to think about that.”