Antibiotics in COPD exacerbation

The use of antibiotics in exacerbations of COPD is based on small placebo-controlled trials and large retrospective population studies. They found that antibiotics improve clinical outcomes in severe COPD exacerbations. There is little evident for the use of antibiotics in mild exacerbation.

A recent cochrane review on the topic concluded that "in COPD exacerbations with increased cough and sputum purulence antibiotics, regardless of choice, reduce the risk of short-term mortality by 77%, decrease the risk of treatment failure by 53% and the risk of sputum purulence by 44%; with a small increase in the risk of diarrhoea These results should be interpreted with caution due to the differences in patient selection, antibiotic choice, small number of included trials and lack of control for interventions that influence outcome, such as use of systemic corticosteroids and ventilatory support. Nevertheless, this review supports antibiotics for patients with COPD exacerbations with increased cough and sputum purulence who are moderately or severely ill".


Choice of antibiotics is an area where not a great deal of evidence exists. Most initial trials were with Amoxicillin, Doxycyclin and Septra. However, these antibiotics are no longer considered first-line for treatment of pathogens such as H.Flu and M. catarrhalis that maybe responsible for COPD exacerbations. When deciding on the antibiotic choice, risk factors such as older age (>65 years), comorbid conditions (especially cardiac disease), severe underlying COPD (defined as FEV1 <50 percent), frequent exacerbations (three or more per year), and antimicrobial therapy within the past three months should be taken into account.

The GOLD guidelines recommend antibiotic therapy for patients with:

1) Severe exacerbation requiring mechanical ventilation
2) With three cardinal symptoms of increased sputum purulence plus either increased dyspnea or increased sputum volume
(thought they don’t provide any guidance regarding the choice of antibiotics)

WITHDRAWN: Antibiotics for exacerbations of chronic obstructive pulmonary disease.
Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, Garcia-Aymerich J, Barnes NC. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004403.

4 for 2, 2 for 4

This morning we reviewed the drugs involved in treatment of active tuberculosis.

The initial phase of treatment usually consists of two months of therapy with four drugs--typically isoniazid, rifampin, pyrazinamide, and ethambutol. The continuation phase in most cases consists of isoniazid and rifampin for four months (remember “4 for 2, 2 for 4”).

Treatment requires careful monitoring for drug toxicity. Baseline transaminases, bilirubin and ALP, CBD, creatinine, and uric acid should be obtained. When starting ethambutol, patients should be referred to ophthalmology for visual acuity and red-green color discrimination testing. Patients should be monitored closely for signs of hepatic toxicity.

Here is a recent update on TB management.
Current concepts in the management of tuberculosis. Sia IG, Wieland ML. Mayo Clin Proc. 2011 Apr;86(4):348-61

* Ghon's complex, seen in left middle field in the above image, is a lung lesion caused by tuberculosis that consists of a calcified focus of infection and an associated lymph node.

The Right dose at the Right time

This morning we discussed a case of fever and headache. We reviewd the approach to diagnosis and treatment of bacterial meningitis. Two key points from our discussion were:

1. Antibiotic therapy should not be delayed for any reason and should be given immediately after blood cultures are obtained. Dexamethasone should be given shortly before or at the same time as the first dose of antibiotics, when S. pneumoniae is suspected.

2. The "meningitis doses" of the empiric antibiotics in patients with normal renal function is: Vancomycin 1.5-2g IV q12, Ceftriaxone 2 g IV every 12 hours, and if Listeria suspected Ampicillin 2gr IV q4hr.


Here is a previous post on Meningitis.

*Steptococcus Pneumoniae, a gram postive cocci in chains, is the most common cause of community acquired bacterial meningitis in adults.

A case of bloody diarrhea

Today we discussed a case of bloody diarrhea caused by Enterohemorrhagic E. coli (EHEC), strain O157: H7.

Patients with this infection generally present with bloody diarrhea, mild leukocytosis, abdominal pain, but no fever. This bacteria produces a toxin called the Shiga toxin which can result in the dreaded Hemolytic-uremic syndrome (HUS)- the major systemic complication of EHEC infection. HUS is characterized by the triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia

The treatment of EHEC infection consists of supportive care and monitoring for the development of microangiopathic complications. Administering antibiotic therapy to patients with EHEC is not recommended (Grade 1B- though the evidence is only in children <10).

Here is a review article on the topic.

Escherichia coli O157:H7 and the hemolytic-uremic syndrome.Boyce TG, Swerdlow DL, Griffin PM. N Engl J Med. 1995;333(6):364.

* Romanian greenhouse employees destroy tons of cucumbers for fear of E. coli. In May 2011, a new Shiga toxin-producing EHEC strain, O104:H4, was identified as the cause of an outbreak in Germany and other countries in Europe.

"a case of abnormal bone softening"

We talked about a case of newly diagnosed Multiple Myeloma. Here is a previous blog post on the topic.

*Sarah Newbury, the first reported patient with multiple myeloma. (A) Bone destruction in the sternum. (B) The patient with fractured femurs and right humerus. (C) Bone destruction involving the femur. Reported by Solly 1844.

Combined ASA and Plavix in setting of Acute Stroke

This morning we talked about the evidence behind dual therapy with ASA and plavix in the setting of acute stroke.

A large study called the MATCH trial, with over 7500 patients, did not find any benefic with the combined use of aspirin and clopidogrel but found significant increase in the risk of bleeding complications.


The FASTER trial, a much smaller study with 392 patients with TIA or mild stroke, compared either aspirin plus clopidogrel (300 mg loading dose, then 75 mg daily) or aspirin alone. The trial ended prematurely due to slow recruitment. At 90 days, there was no statistically significant difference between the groups but a trend toward decreased primary outcome measure of combined ischemic and hemorrhagic stroke (7.1 versus 10.8 percent).

Silk Road Disease

This morning we discussed a case of oral ulcers and our differential diagnosis included Behcet’s disease.

This disorder is a systemic vasculitis that can effect veins of variable sizes. The disease is characterized by relapsing episodes of oral and genital ulcers, skin lesions, and ocular lesions, and can affect other systems including vascular, gastrointestinal, and neurological systems.

It occurs most frequently in an area that coincides with the Old Silk Route, so the disease is sometimes referred to as the Silk Road Disease.

Mainstay of treatment is immunosuppression with corticosteroids, azathioprine, cychlophosphamide, cyclosporine A, and more recently biologics including interferon-alpha, anti-tumour necrosis factor alpha agents.


Here is a recent feview article on the topic.

Behçet's disease--a contemporary review. Mendes D, Correia M, Barbedo M, Vaio T, Mota M, Gonçalves O, Valente J. J Autoimmun. 2009 May-Jun;32(3-4):178-88. Epub 2009 Mar 26.


* The image is a picture of Hulusi Behçet, a Turkish dermatologist and scientist who first described the illness in 1936.

Tachycardia-induced Cardiomyopathy

We discussed a case of tachycardia-induced cardiomyopathy this morning. This condition results from prolonged periods of rapid ventricular heart rates, and often improves with heart rate control with a good prognosis in most patients.

Patients may present with palpitations, fatigue, decreased exercise tolerance, or symptomatic congestive heart failure.

Treatment of tachycardia-mediated heart failure is the same as any other heart failure (eg, ACE or ARB inhibitors, beta blockers, diuretics), with aggressive control of heart rate.

Here is a recent review article on the topic

Tachycardia-induced cardiomyopathy: evaluation and therapeutic options. Lishmanov A, Chockalingam P, Senthilkumar A, Chockalingam A. Congest Heart Fail. 2010 May;16(3):122-6.


* Chest x ray showing cardiomegaly (panel A) in a patient with tachycardia (panel B). Panel C shows improved cardiomegaly after 3 months of aggressive heart-rate control (panel D). Images in Cardiology. Heart 2001;86:642.

Diabetic Autonomic Neuropathy

This morning our we talked about diabetic autonomic neuropathy (DAN) in long-standing diabetes.

DAN is a common and distressing complication that can affect any or all parts of the autonomic nervous system (ANS). Many organs are innervated dually by the parasympathetic and sympathetic fiber. DAN can cause hypo- or hyperactivity of each or all parts of the ANS.

Clinical manifestations can include the cardiovascular system (tachycardia, exercise intolerance, cardiac denervation leading to silent ischemia, orthostatic hypotension), GI system (esophageal dysfunction, gastroparesis, diarrhea or constipation, fecal incontinence), GU system (erectile dysfunction, neurogenic bladder), skin (impaired sweating), and metabolic dysfunction(hypoglycaemia unawareness).

Here a review article on the topic.
Diabetic autonomic neuropathy. Vinik AI, Freeman R, Erbas T. Semin Neurol.(4):365-7.

* A plain abdominal radiograph showing a very dilated stomach (arrows) secondary to diabetic autonomic neuropathy (Images in Clinical Medicine NEJM)

Water Intoxication

This morning, we discussed a case of hyponatremia.

Remember that disorders of sodium are really problems with water balance, so it is helpful to think of hyponatremia as excess free water. Prior to being able to test for serum sodium concentrations, the clinical syndrome that is now known as hyponatremia, characterized by confusion, muscle cramps, fatigue, delirium, seizures, and death, was called “water intoxication” syndrome.

Here are two previous post on hyponatremia.
Hyponatremia
Hyponatremia - no it's Hyperhydroemia


* MRI scan of person with central pontine myelinolysis (Saggital view, the dark area inside the circle is the region of damage). CPM is a devastating consequence of rapid fluctuations in sodium status.

Equilibrium

Today in morning report a few of the presented cases had disorders of equilibrium with the two cardinal symptoms of either vertigo – an illusion of bodily or environment spinning- or ataxia- incoordination of limbs or gait.

Disorders of disequilibrium can be produced by conditions that affect the vestibular pathways, the cerebellum, or sensory pathways in the spinal cord or peripheral nerves.

We considered the diagnosis of stroke in all of the above cases. A recent article in CMAJ called "Does my dizzy patient have a stroke" addresses that same question. Here is the article.

*Jean Louis Forain's 19th Century Tightrope Walker. How many organ systems is the performer using to maintaining her balance in the dark?

Is This Patient Malnourished?

In our physical exam rounds today, we examined a patient for signs of malnutrition, and reviewed the JAMA RCE article on the topic.

The gist of the articles is to know the “Subjective Global Assessment” which includes the following:
•History (Weight change,Dietary intake change,GI symptoms,Functional capacity)
•Physical exam (Loss of subcutaneous fat, Muscle wasting, Edema)

Based the above, you can categorize patients into “well-nourished”, “moderately malnourished”, or “severely malnourished”. These categories then correlate with patient likelihood of being admitted, and post-operative complications.

Here is the article.
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed?term=is%20this%20patient%20malnourished%20detsky%20JAMA

* Given our topic of conversation, I like to remind everyone of the famine in East Africa. A devastating drought and crumbling infrastructure have created one of the worst hunger emergencies in our generation. If you would like to make a donation, the Government of Canada has created the East Africa Drought Relief Fund, and will match your donations.

An aspirin a day? ASA in secondary prevention of CVD.

This morning we briefly mentioned the Antithrombotic Trialists' Collaboration overview article. This group reviewed the results of 195 randomized trials of aspirin, among more than 135,000 high-risk patients with prior history of cardiovascular or cerebrovascular events. The following are the major conclusions:

• Aspirin, significantly reduced the relative risk of subsequent vascular events (nonfatal MI, nonfatal stroke, and vascular death) by approximately 22 percent.
• There was no difference in efficacy between doses of 75 to 150 mg/day (called low-dose aspirin) and 160 to 325 mg/day (called medium-dose aspirin).

Here is the link to the paper if you like.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Antithrombotic Trialists' Collaboration. BMJ. 2002;324(7329):71.

http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed?term=BMJ.%202002%3B324(7329)%3A71.

* A French advertisement for aspirin from 1923. Aspirin (name originally coined by they Bayer company in 1897) lost its status as a registered trademark became a generic name in many countries. Today, Aspirin, with a capital "A", remains a registered trademark of Bayer Canada.