I would like like to add a little update on clinical management. These updates are taken from UpToDate and are current upto Feb 2019.
How long should Gram negative bacteremia with enterobacteracae be treated?
A patient with uncomplicated Gram negative bacteremia with enterobacteracae who is responding to therapy should be treated for 7 days not 14 days. This is the recommendation for patients with no co-morbid conditions which are likely to alter the prognosis.
Gram-negative bacilli are the cause of approximately a quarter to a half of all bloodstream infections, depending on geographic region, hospital- or community-onset, and other patient risk factors such as diabetes, kidney failure, liver failure or immunosuppression.
Enterobacteracae are Gram negative bacteria many of which are symbiotic organisms and only cause disease in unusual circumstance. The pathogens include salmonella, eschirechia coli, yersinia pestis, klebsiella and shigella. Other disease causing bacteria in this family include proteus, enterobacter, serratia and citrobacter.
These bacteria may produce Class A beta-lactamase which includes Klebsiella pneumoniae carbapenemase (KPC), Class B beta-lactamase which includes the New Delhi metallo-beta-lactamase (NDM-1)
They may be resistant to the penicillins, cephalosporins, and carbapenems. Resistance genes for other antibiotics, including aminoglycosides and fluoroquinolones may be present. We are getting very close to the super bug!🤢
What treatment to use for these organisms? It depends o the degree of susceptibility. Suggested antibiotic combinations; ceftazidime-avibactam (add a carbepenam if necessary): meropenem-vaborbactam is another agent that can be used for KPC-producing organisms. Colistin can be a useful antibiotic
Aspirin for primary prevention of cardiovascular disease and cancer.
A 42 year old man consults you about whether he is at risk for ischemic heart disease? He has no symptoms and his ECG, exercise tolerance test and echocardiogram are normal. His father who is 75 years old has had 2 heart attacks and has been on aspirin for 6 years. He developed dyspepsia some months ago. His doctor has stopped the aspirin. The man wants to know whether taking aspirin regularly for the rest of his life is advisable? Is it safe for his father to stop aspirin?
Why should we not prescribe aspirin to all?
Primary prevention with aspirin is appropriate for most patients over age 40, but now the decision whether to use aspirin for primary prevention of cardiovascular disease and cancer should be made based on shared decision-making, taking into account the probable benefits and harms of aspirin relative to the specific patient.
In secondary prevention of cardiovascular disease (CVD), the absolute benefits of aspirin on occlusive cardiac or neurological events are greater than the absolute harm of major bleeding unless the patient is over 70-years-old.
For primary prevention, three recent large randomized trials evaluating all-cause mortality associated with aspirin use indicate that the benefits and harms of aspirin for primary prevention are very closely balanced. In both the ASCEND trial in patients with diabetes as well as the ARRIVE trial in patients with moderate CVD risk, the risk of all-cause death was similar with or without aspirin.
In the ASPREE trial of individuals 70 years or older, the risk of death was higher with aspirin (13 versus 11 percent). The decision whether to use aspirin for primary prevention should be made only after a detailed discussion between the patient and health care provider, guided by personal patient preferences and estimated benefits and harms relative to the specific patient. The balance between benefits and harms may weigh more heavily for harms over benefits in those over 70 years of age.
Answer. For the young man as he is at moderate risk of CVD if he is not obese, or a smoker or a diabetic, Taking aspirin regularly is a personal decision as the trials show that the all cause mortality will not be significantly affected. For the father stopping the aspirin is more likely to be helpful than harmful.
Dabigatran for patients with myocardial injury after non-cardiac surgery (MINS).
For patients with perioperative myocardial infarction or myocardial injury after non-cardiac surgery (MINS) who are not at increased bleeding risk, treatment with dabigatran 110 mg twice daily for two years.
Patients with myocardial injury after non-cardiac surgery (MINS) are at increased risk for short- and long-term adverse cardiovascular outcomes. All such patients should be treated with aspirin and a statin. In the MANAGE trial, over 1750 MINS patients were randomly assigned to dabigatran 110 mg or placebo twice daily for a maximum of two years. Dabigatran treatment lowered the risk of major vascular complications (vascular mortality and nonfatal myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism) compared with placebo (11 versus 15 percent). The risk of major bleeding was similar between the groups (3 versus 4 percent). Adding dabigatran for two years to standard management of patients with MINS is advisable.
Transcatheter mitral valve repair for secondary mitral regurgitation
For most patients with moderate-to-severe or severe (3+ to 4+) chronic secondary mitral regurgitation and heart failure despite optimum management, we suggest referral to a Heart Valve Team to assess the feasibility and potential benefit and risk of transcatheter mitral valve repair (TMVR) (Grade 2B).
Two randomized trials assessing the efficacy of transcatheter mitral valve repair (TMVR), compared with continued medical therapy for patients with secondary mitral regurgitation (MR), have found conflicting results. At two-year follow-up, TMVR reduced mortality and hospitalization for heart failure in the COAPT trial, involving over 600 patients.
Primary MR is caused by disease or damage of the leaflets or other valve apparatus. Chronic secondary MR (also known as functional MR) is caused by left ventricular dysfunction in the presence of undamaged mitral valve leaflets. The common cause is heart failure following ischemic heart disease or cardiomyopathy.
Staging — Staging of secondary MR is based upon symptoms, valve anatomy, and valve hemodynamics (severity of MR), which are associated with LV dysfunction (due to coronary artery disease [CAD] or cardiomyopathy) as described in the 2017 focused update of the 2014 American Heart Association (AHA)/American College of Cardiology (ACC) valvular heart disease guideline. After optimal therapy to improve cardiac function and resynchronisation therapy the patient should be referred to a team of cardiac surgeons and cardiologists who can manage the transcatheter repair. Is it indicated? Transcatheter repair can be combined with revascularisation procedures which the patient may also require. However, for some patients durable TMVR is not feasible or appropriate due to technical issues, or if life expectancy (with TMVR) is less than one year, or comorbidities exist limiting the likelihood of improvement in the patient’s quality of life.
Two trials, the MITRA-FR randomized trial enrolled 304 patients with moderate to severe (2+ to 4+) secondary MR, an LVEF of 15 to 40 percent, and symptomatic HF. The mitroclip procedure was used but the results did not show significant benefit. The COAPT trial was larger, enrolled 614 patients, included longer follow-up and included patients with higher brain natriuretic peptide levels (mean 1043 versus 800 ng/L) and more severe MR (mean effective regurgitant orifice area 40.5 versus 31 mm2. When viewed together the results of these two trials showed benefit for the transcatheter repair of the mitral valve.
What questions are to be expected?
A 71-year-old man has had ischemic heart disease for the past 14 years. He had angioplasty and stenting 2 years ago. He has heart failure and gross functional MR, He needs a pacemaker because he has recurrent SVT.
What treatment is advisable?
Patients with chronic secondary MR and HFrEF should receive standard evidence-based therapy for HFrEF, including angiotensin converting enzyme inhibitor (ACE) inhibitor (or angiotensin II receptor blocker [ARB], or angiotensin receptor-neprilysin inhibitor [ARNI]), beta blocker and mineralocorticoid receptor antagonist (if indicated), and diuretic therapy as needed to treat volume overload.
What does he need to treat the arrhythmia?
He need to have a pacemaker put in.
He is not improving with diuretics, nitrates, statins, aspirin and ACE-I and aldosterone. He is not diabetic and hypertension is controlled.
What investigations will you do for him?
Do echocardiogram studies to stage his MR. Investigate his renal status, status of diabetes, lipid studies.
Can you offer him any other treatment?
Transcatheter mitral valve repair if the facilities exist in your part of the world,