Sepsis and Septic Shock Guidelines

One of the main guidelines in sepsis is the Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock from 2012 (updating the 2008 guidelines).

Pocket Guide

Key recommendations and suggestions:

• Early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C)
• Blood cultures before antibiotic therapy (1C)
• Imaging studies performed to confirm a potential source of infection (UG)
• Administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B)
• Infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C)
• Initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C)
• Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to acheive a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C)
• Fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG)
• Norepinephrine as the first-choice vasporessor to maintain mean arterial pressure >/= 65 mm Hg (1B)
• Epinephrine when an additional agent is needed to maintain adequate blood pressure (2B)
• Vasopression (0.03 U/min) can be added to NE to either raise MAP to target or to decrease NE dose but should not be used as the initial vasopressor (UG)
• Dopamine is not recommended except in highly selected circumstances (2C)
• Dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite acheiving adequate intravascular volume and adequate MAP (1C)
• Avoiding use of IV hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C)
• Hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B)
• Low tidal volume (1A) and limiation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS)
• Application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B)
• Higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C)
• Recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C)
• Prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of </= 100 mm Hg in facilities that have experience with such practicees (2C)
• Head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B)
• A conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C)
• Protocols for weaning and sedation (1A)
• Minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B)
• Avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C)
• A short course of neuromuscular blocker (no longer than 48 hours) for patients with early ARDS and a PaO2/FIO2 < 150 mm Hg (2C)
• A protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose </= 180 mg/dL (1A)
• Equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B)
• Prophylaxis for deep vein thrombosis (1B)
• Use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B)
• Oral or enteral (if necessary) feedings, as tolerated, rathern than either complete fasting or provision of only IV glucose with the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C)
• Addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hours of intesive care unit admission (2C). 

Leaving the Anti-Vaccine Movement

The anti-vaccine movement had me in its grips after the early birth of my first child In 2008. My son's lungs were not fully developed, and he needed the NICU. My husband and I had signed up for a "natural" childbirth class where epidurals were evil and rupture of membranes did not mean go to the hospital. We were also told to forgo the hepatitis B vaccine for our newborns because "babies don't have sex or do illicit drugs by injection." I am a hospital pharmacist and was falling for it all.

Jenny McCarthy and Dr. Andrew Wakefield were regularly in the news for the connection between vaccines and autism, and I was fearful for my son. After all, Dr Wakefield was a physician with a research paper in support of the connection between vaccines and autism. Also it was a little bit popular to be anti-vax.

Herd immunity is a form of immunity that results when the vaccination of a significant portion of the population provides a measure of protection for those who have not developed immunity. Herd immunity disrupts normal transmission of diseases covered by vaccination. The anti-vax movement directly compromises this immunity resulting in less people becoming vaccinated and increases in diseases that were virtually eradicated.

Measles is on the rise. Dr. Mark Grabowsky, a health official with the United Nations, wrote last year in the Journal of the American Medical Association-Pediatrics. “Many measles outbreaks can be traced to people refusing to be vaccinated; a recent large measles outbreak was attributable to a church advocating the refusal of measles vaccination.” Measles was once considered eradicated. For every 1,000 children who get the measles, one or two will die from it, and one will get brain swelling so severe it can lead to convulsions and leave the child deaf or mentally impaired, the U.S. Centers for Disease Control and Prevention said. In contrast the fears parents have to vaccinate in relation to autism and MMR according to the Wakefield study continues to rise even though the study was proven false. Wakefield was stripped of his license to practice medicine, and numerous conflicts of interest surrounding the study were discovered. Once upon a time before vaccinations, nearly everyone in the U.S. got measles before there was a vaccine, and hundreds died from it each year. Today, most doctors have never seen a case of measles, but cases keep popping up, the latest starting in Disneyland.

Still the anti-vax movement continues. 

Mumps have also made a comeback. Before widespread vaccination, there were about 200,000 cases of mumps and 20 to 30 deaths reported each year in the USA. Mumps can in some cases lead to encephalitis and deafness. Herd immunity is important because the mumps vaccine is just 88% effective, explaining why someone can easily contract the disease even if they have been vaccinated as I did back in 9th grade from a foreign exchange student. I was vaccinated, but for whatever reason was infected from someone overseas. The CDC reports that the number of mumps cases doubled in the past year - affecting more than 1,000 people nationwide.

Mumps in the United States from 1970-2005

Mumps in the United States from 1980-2005

Pertussis or whooping cough was a universal disease in the pre-vaccination era was almost always seen in children. Between 1940 and 1945, before widespread vaccination, as many as 147,000 cases of pertussis were reported in the USA each year, with approximately 8,000 deaths caused by the disease. It is estimated that at the beginning of the 20th century as many as 5 of every 1000 children born in the USA died from pertussis.

Pertussis in the US from 1940-2000

Pertussis in the US from 1980-2005 (on the rise)

Why don't parents vaccinate today? Parents today did not grow up with these diseases and see the thousands of children die. We are not afraid of these diseases because they have not been a part of our lives and take for granted how these diseases can cause death or severe consequences. Parents hear celebrities like Jenny McCarthy, Alicia Silverstone and Kristin Cavallari cite fear as a reason not to vaccinate. But what many don't realize is that those against vaccines and not vaccinating their children depend on the rest of us to vaccinate to stay safe. The more people that join in the crusade that vaccines are evil, the higher the risk their own children will succumb to diseases that were virtually gone just a few years ago. 

Side effects of vaccines are mild according to the CDC. And while there are very rare cases of vaccine-related issues, the benefit far outweighs the risk if you compare the numbers pre-vaccination era vs. after vaccinations were introduced.

Why should parents vaccinate? Parents should vaccinate because vaccines are preventing complications from preventable childhood illnesses that can cause deafness, blindness, hospitalization, other life altering effects and death. Parents should become informed and become critical thinkers about the decisions made to increase the risk of these diseases to their children and others who are unable to fight infection (elderly, immunodeficiencies, and the very young). Parents should not, as I did, make decisions by fear and paranoia and look at the facts. We should also as a society consider public health and realize that vaccines are safe and very effective and not vaccinating is irresponsible.

Fortunately, I woke up from the "anti-vax movement" before endangering my son further. Although his vaccines were spaced out individually and further apart, he ended up receiving them all. My daugther, on the other hand, received them all on time as outlined by the CDC. I do have much greater peace of mind knowing the numbers don't lie, vaccines save lives and have since they were first introduced years ago. I am glad I did not let the fear of the unknown and debunked guide my choices to put them in harm's way.

Cephalosporins Are Not Created Equal

Just the other day I found where a pharmacist had discontinued cefepime off a patient's profile because a post-op order had included starting cefazolin post-op for three doses.  This particular patient had pseudomonas positive cultures, and I scratched my head trying to figure out why the cefepime was stopped.

Well...

Our computer system flags cephalosporins as duplicates regardless of what generation and what is being treated.  It is much too easy as a pharmacist to just allow the computer system to do all the thinking, but if you have an archaic computer system as many hospitals I have seen, well...

So here's a cephalosporin refresher.  Maybe some tips to help you remember things about each generation and why cefepime is not the same as cefazolin.  NEVER ever.

Some hints to just memorize I use:  (I did not create these)

How to remember the names of the MC used drugs third generation Cephalosporins? Easy. Third Generation–>cef-Tazidime,cefo-Taxime, and cef-Triaxone. All of them start with CEF (they are Cephalosporins) and have the letter T in their name, right after CEF. There is an exception of that rule. Cef-oTeTan is a second generation Cephalosporin, starts with CEF and has the letter T in its name. It can’t be easier than that. Second generation=IInd. generation–>double T in the name of Cef-oTeTan.

1st: zolin, lexin are dying.

cefazolin, cephalexin, cephradine

2nd: actor fox, u rocks (most don't enter CNS)

actor: cefaclor, fox: cefoxitin, u rocks: cefuroxime

A Fox has a Furry Face ie ceFOXitin, ceFURoxime ceFAClor

3rd: tazi tri taxi enter CNS, opera no CNS

tazi: ceftazidime, tri: ceftriaxone, taxi: cefotaxime

oper: cefoperazone (doesn't enter CNS, from kaplan)

4th:  cefepime

From the fpnotebook.com:

1. General
   1. Spectrum changes from first to third generation
      1. First Generation: Better Gram Positive Cocci coverage
      2. Third Generation: Better Gram Negative Rod coverage
2. Contraindications
   1. Drug allergy to other Cephalosporin
   2. Type I Hypersensitivity Reaction to a Penicillin
      1. Less than 10% of those who report Penicillin Allergy actually have a Penicillin Allergy
      2. Penicillin Allergy has only a 1% risk of cross-reactivity with Cephalosporins (previously thought to be 10%)
         1. Herbert (2000) West J Med 172(5): 341
      3. Penicillin Anaphylaxis confers a 0.001% risk of Anaphylaxis to Cephalosporins
         1. Apter (2006) Am J Med 119(4):354.e11-9
      4. Cross reactivity appears limited to First Generation Cephalosporins and Penicillins
         1. Second and Third Generation Cephalosporins have minimal to no allergy cross reactivity
         2. Campagna (2012) J Emerg Med 42(5): 612-20
3. Class: First Generation Cephalosporins
   1. Oral Agents
      1. Cephalexin (Keflex)
      2. Cephradine (Velosef)
      3. Cefadroxil (Duricef)
   2. Parenteral Agents
      1. Cefazolin (Ancef)
   3. Organisms covered
      1. Gram Positive Cocci
      2. EKP Gram Negative Bacteria
4. Class: Second Generation Cephalosporins
   1. Second Generation Broad-spectrum Cephalosporins
      1. Oral Agents
         1. Loracarbef (Lorabid)
         2. Cefprozil (Cefzil)
         3. Cefuroxime (Ceftin, Zinacef)
         4. Cefaclor (Ceclor)
      2. Organisms Covered
         1. Gram Positive Cocci
         2. EKP Gram Negative Bacteria
         3. Gram Negative Coccobacilli
   2. Second Generation Anti-anaerobe Cephalosporins
      1. Parenteral Agents
         1. Cefoxitin
         2. Cefotetan
         3. Cefamandole
      2. Organisms Covered
         1. Bacteroides fragilis
5. Class: Third Generation Cephalosporins
   1. Third Generation Broad-Spectrum Cephalosporins
      1. Oral agents
         1. Cefixime (Suprax)
            1. Only indication is for Gonorrhea
         2. Cefpodoxime (Vantin)
            1. Does not cover Enterobacter or pseudomonas
      2. Parenteral agents
         1. Cefotaxime (Claforan)
         2. Ceftizoxime (Cefizox)
         3. Ceftriaxone (Rocephin)
      3. Organisms Covered
         1. Gram Positive Cocci
         2. EKP Gram Negative Bacteria
         3. ESP Gram Negative Bacteria
         4. No Pseudomonas activity
   2. Third Generation Anti-Pseudomonal Cephalosporins
      1. Agents
         1. Ceftazidime (Fortaz)
      2. Organisms Covered
         1. Pseudomonas
         2. EKP Gram Negative Bacteria
         3. ESP Gram Negative Bacteria
         4. Poor Gram Positive Cocci coverage
         5. No Coccobacilli coverage
   3. Fourth Generation Cephalosporins --Cefepime -  is a fourth-generation cephalosporin antibiotic developed in 1994. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both Gram-negative and Gram-positive organisms than third-generation agents.Cefepime is usually reserved to treat moderate-severe nosocomial pneumonia, infections caused by multi-resistant microorganisms (e.g.Pseudomonas aeruginosa) and empirical treatment of febrile neutropenia.^[3]

      Cefepime has good activity against important pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, and multiple drug resistant Streptococcus pneumoniae. A particular strength is its activity against Enterobacteriaceae. Whereas other cephalosporins are degraded by many plasmid- and chromosome-mediated beta-lactamases, cefepime is stable and is a front line agent when infection with Enterobacteriaceae is known or suspected.

So there you go.

Don't go discontinuing a broad spectrum cephalosporin used to treat a multi-resistant microorganism like Pseudomonas for a puny mostly gram positive post surgical cefazolin for they are not equal.

And that would be an awesome song lyric!

BCPS 2013: Infectious Disease (Pneumonia)

Infectious Disease.  The topic that I like but loathe.  At the same time. Pneumonia

1. Community Acquired Pneumonia (CAP) - not hospitalized 2 days or more within the past 90 days, not in a LTC facility/residence, no IV antibiotic therapy, IV chemo, or wound care in the past 30 days, or attendance at a hospital or dialysis clinic.  Must have at least two of the following symptoms:  fever or hypothermia, rigors, sweats, new cough (with or without sputum), chest discomfort, onset of dyspnea, or fatigue, pain, headache, myalgias, anorexia.CURB-65 - predictor of complicated course and whether to admit to the hospital.  Give a point for each of the following:  age > 65, comorbid illnes (DM, CHF, lung dz, renal dz, liver dz), high temp > 101F, Bacteremia, altered mental status (think elderly), immunosuppression (cancer, steroid use), High-risk etiology (S. aureus, legionella, G- bacilli, anaerobic aspiration), multilobe involvement or pleural effusion.
2. Nosocomial Pneumonia:  Hospital Acquired Pneumonia (HAP) (48 hours or more after admission), Ventilator Assoc Pneumo (more than 48–72 hours after intubation), Health care Assoc Pneumo (2 or more days within 90 days of the infection) - know risk factors of nosocomial pneumonia.  Pretty common sense.
3. CAP Organisms:  Unidentifiable (40-60%), M.pneumo, S. pneumo, H.flu, C.pneumo, viruses, S. aureus, Moraxella cat,
4. Alcoholics - S. pneumoniae, oral anaerobes, gram negative bacilli
5. Nursing Home - S. pneumoniae, H. influenzae, gram negative bacilli, S. aureus
6. COPD - S. pneumoniae, H. influenzae, M. catarrhalis
7. Postinfluenza: H. influenzae, S. aureus, S. pneumoniae
8. Exposure to water: Legionella
9. Poor oral hygiene: oral anaerobes
10. HIV infection: P. jiroveci, S. pneumoniae, M. pneumoniae, Mycobacterium

HAP Organisms:  S. aureus, Pseudomonas aeruginosa, Enterobacter spp., Klebsiella pneumoniae, Candida, Acinetobacter spp., Serratia marcescens, Escherichia coli, S. pneumoniae

P. aeruginosa is transmitted by health care workers’ hands or respiratory equipment S. aureus is transmitted by health care workers’ hands Enterobacteriaceae endogenously colonize hospitalized patients’ airways (healthy people seldom have gram negative upper airway colonization) Stress changes respiratory epithelial cells so that gram-negative organisms can adhere Up to 70% of patients in the intensive care unit have gram-negative upper airway colonization, and 25% of them will become infected through aspiration

TREATMENT

CAP - duration of treatment at least five days:

Empiric nonhospitalized - prev healthy and no abx in past 3 mos - macrolide or doxy (macrolide if H.flu suspected) and if comorbidities present or recent antibiotics in past 3 months - Respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg])

-- OR -- Macrolide (or doxycycline) with high-dose amoxicillin (1 g 3 times/day) or amoxicillin/clavulanate (2 g 2 times/day) or with a cephalosporin (ceftriaxone, cefuroxime, or with cefpodoxime)

Empiric treatment of hospitalized patients with moderately severe pneumonia - Respiratory fluoroquinolone

--OR-- Ampicillin, ceftriaxone, or cefotaxime (ertapenem in select patients) plus a macrolide (or doxycycline)

Empiric treatment of hospitalized patients with severe pneumonia requiring intensive care unit treatment (may need to add other antibiotics if P. aeruginosa or MRSA is suspected)

• Ampicillin/sulbactam plus either a respiratory fluoroquinolone or azithromycin
• Ceftriaxone plus either a respiratory fluoroquinolone or azithromycin
• Cefotaxime plus either a respiratory fluoroquinolone or azithromycin

Treatment duration—at least 5 days, with 48–72 hours afebrile and no more than one sign of clinical instability (elevated temperature, heart rate, or respiratory rate; decreased systolic blood pressure; or arterial oxygen saturation) before therapy d/c

Hospital Acquired Pneumonia - Treatment duration—Efforts should be made to decrease therapy duration to as short as 7 or 8 days (14 days for pneumonia secondary to P. aeruginosa).

1. Early onset (less than 5 days) and no risk factors for multidrug-resistant organisms -  Common organisms include S. pneumoniae, Haemophilus influenzae, (MSSA), Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., and Proteus spp. -- Treatment -- Third-generation cephalosporin (cefotaxime or ceftriaxone), Fluoroquinolone (levofloxacin, moxifloxacin, ciprofloxacin), Ampicillin/sulbactam, OR Ertapenem
2. Late onset (5 days or longer) or risk factors for MDR organisms - Common organisms include those listed above for early onset plus Pseudomonas aeruginosa, K. pneumoniae (extended spectrum β-lactamase positive), Acinetobacter spp., MRSA, and Legionella pneumophila. -- Treatment -- a.  Ceftazidime or cefepime plus aminoglycoside or fluoroquinolone (cipro-, levo-)  b.  Imipenem, meropenem, or doripenem plus aminoglycoside or fluoroquinolone (ciprofloxacin, levofloxacin), OR c.  Piperacillin/tazobactam plus aminoglycoside or fluoroquinolone (ciprofloxacin, levofloxacin)  ***Vancomycin or linezolid should be used only if MRSA risk factors (e.g., history of MRSA infection/colonization, recent hospitalization or antibiotic use, presence of invasive health care devices) are present or there is a high incidence locally (greater than 10%–15%).

Risk factors for MDR organisms -- Antibiotic therapy within the past 90 days, Hospitalization of 5 days or more, High resistance in community or hospital unit, Risk factors for health care–associated pneumonia, Immunosuppressive disease and/or therapy

A wonderful article published just last November that I love.  (Pharmacy Times)  Only thing is it doesn't go into the detail of the different antibiotics with Late vs Early Onset of Hospital Acquired.  Just CAP.  That's OK

And because guidelines haven't changed, my quizlet from last year.  Hope you enjoy:

BCPS 2013: Pediatrics Otitis Media

Such a fun topic!  Who loves it when the kid says his/her ear hurts?  I cringe just thinking about this one: Otitis Media:  The Bane of all Daycare and all School-aged Youngsters

Common Pathogens

• Viral
• S. pneumoniae
• Nontypeable H. influenzae
• Moraxella catarrhalis

Treatment

• Watch and wait if > 2 yo and pain/fever less than 48-72 hours
• Bulging tympanic membrane/perforation = antibiotics
• Always antibiotics if < 6 months old 4. Middle ear fluid does not indicate repeated treatment unless persists > 3 months
• Corticosteroids, antihistamines, and decongestants are not recommended

Antibiotic regimens a. Amoxicillin (high dose: 80–90 mg/kg/day): Recommended by AAP as the first-line therapy for acute otitis media b. Amoxicillin/clavulanate c. Cefuroxime d. Other antibiotic options (e.g., cefdinir, cefpodoxime) may be effective. e. Duration i. The most appropriate duration is unclear. ii. In general, 7–10 days, but a shorter course (5 days) has been used in children older than 2 years iii. For confirmed cases of acute otitis media not responding to the initial antimicrobial regimen within 48–72 hours, a change in antibiotic regimen is warranted. Failure of the the above warrants ceftriaxone IM for 3 days or tubes i. Intramuscular ceftriaxone may also be considered if adherence is a concern. ii. Tympanostomy with tube placement may be most beneficial for children with persistent otitis media with effusions and significant hearing loss (e.g., greater than 25-dB hearing loss in both ears for more than 12 weeks).

Prophylaxis 1. Reserved for patients with recurrent acute otitis media 2. Reduces occurrence by about one episode per year 3. The risk of promoting bacterial resistance may outweigh the slight benefit

BCPS 2013: Pediatrics

I feel I have a bit of insight into the test and can attest to what is needed to know in each section.  Keep in mind the guidelines could change between 2012 and 2013 along with the test questions, but for the most part I found the test to be incredibly fair though stressing areas more than others that I would have not expected. I want you to pass!  First attempt!

So what do you need to do to pass?  Start now.  I especially am talking to those with families and/or children and very little time to spare for sitting down and studying the traditional way.  Again, I did fail this past year, so I will disclose that immediately, but I do believe I have insight into the test and very much plan to pass it this fall.  It's a goal at this point for my own personal development.

So, ahead I will have some material presented that does come from the ACCP study material though reworded and simplified in more study form and perhaps some hints as to what was important on the test in each particular section.  I am hoping to not get in any sort of trouble by doing this as far as with the BPS, so if this is not appropriate, would someone from there contact me?  I do not plan on giving test questions per se' and I couldn't if I tried as there were far too many to memorize.

After two children I am convinced parts of my brain were delivered with the children as it is.

First up!  PEDIATRICS!

This was always the topic that would terrify me prior to having children, but at this point besides missing one of the most common concepts of children and the very small amount of data on the test regarding pediatrics (at least in my opinion), pediatrics just doesn't seem so daunting.

Know the common pathogens of children in sepsis and meningitis.

0–1 month  

• Group B streptococcus
• Escherichia coli
• Listeria monocytogenes
• Viral (e.g., herpes simplex virus)
• Coagulase-negative staphylococcus—nosocomial
• Gram (−) bacteria (e.g., Pseudomonas spp., Enterobacter spp.)
• nosocomial

1–3 months

• Neonatal pathogens (see above)
• Haemophilus influenzae type B
• Neisseria meningitidis
• Streptococcus pneumoniae

3 months–12 years

• H. influenzae type Ba
• N. meningitidis
• S. pneumoniae

> 12 years

• N. meningitidis
• S. pneumonia

Not to hard to figure out correct?  Keep in mind that H. flu is less and less due to immunizations.  I suppose if you live in an area where vaccination is the devil, you may find more of this organism.

Potential Antibiotic Regimens

Age                                                                         Regimen

0–1 month                                                            Ampicillin + gentamicin OR ampicillin + cefotaxime

1–3 months                                                          Ampicillin + cefotaxime/ceftriaxone

3 months–12 years                                             Ceftriaxone ± vancomycina

> 12 years                                                             Ceftriaxone ± vancomycina

**Addition of vancomycin should be based on the regional incidence of resistant S. pneumoniae.

Regimens for Chemoprophylaxis  (I will have to reformat this later)

Drug                      Neisseria meningitidis                                                                       Haemophilus influenzae

Rifampin            < 1 month old: 5 mg/kg/dose PO every 12 hours × 2 days                       20 mg/kg/dose (maximum 600 mg)

> 1 month old: 10 mg/kg/dose PO every 12 hours × 2 days                   daily x 4 days

Adults: 600 mg PO every 12 hours × 2 days

Ceftriaxone             < 15 years old: 125 mg IM × 1 dose                                                               Not indicated

> 15 years old: 250 mg IM × 1 dose

**Ciprofloxacin and azithromycin are possible alternatives although not routinely recommended.

RSV - Identify the drugs available for preventing and treating respiratory syncytial virus.

Prophylaxis

1. Nonpharmacologic: Avoid crowds during RSV season and conscientiously use good hand-washing practice.
2. RSV IVIG (RespiGam): No longer marketed in the United States (didn't see on the test ;))
3. Palivizumab (Synagis)

• a. Dosing: 15 mg/kg/dose intramuscularly; given monthly during RSV season
• b. Effects on outcomes

i. A 55% reduction in hospitalizations for RSV

ii. Safe in patients with cyanotic congenital heart disease

iii. No reduction in overall mortality

iv. Does not interfere with the response to vaccines

v. Not recommended for the prevention of nosocomial transmission of RSV

Know this:  Supportive care.  Treatment is supportive care only.

American Academy of Pediatrics Palivizumab approval:  (you WILL see this)

i. Premature infants born before 32 weeks’ gestation (i.e., 31 weeks, 6 days or earlier) who are 6 months old or younger at the beginning of RSV season

(a) Infants born at less than 28 weeks’ gestation may benefit up to 12 months of age.

(b) Eligible for a maximum of five doses of palivizumab during RSV season

ii. Infants with chronic lung disease who are 2 years or younger and who required medical management of their chronic lung disease in the previous 6 months – Eligible for a maximum of five doses of palivizumab during RSV season

iii. 32 and 35 weeks’ gestation (i.e., 32 weeks, 0 days through 34 weeks, 6 days) who are 3 months or younger at the beginning of RSV season

(a) With at least one of the following risk factors may benefit: infant attends childcare or sibling younger than 5 yo in same household

(b) Eligible for a maximum of three doses of palivizumab during RSV season

iv. Infants 24 months and younger with hemodynamically significant congenital heart disease

(a) Eligible for a maximum of five doses of palivizumab during RSV season

(b) There is a 58% decrease in palivizumab serum concentration after cardiopulmonary bypass; therefore, a postoperative dose of palivizumab is recommended as soon as the patient is medically stable.

v. Infants 12 months and younger with congenital abnormalities of the airway or neuromuscular disease that compromises the handling of respiratory tract secretions – Eligible for a maximum of five doses of palivizumab during RSV

Tomorrow will continue with otitis media...

All Things Vancomycin

Believe it or not, vancomycin was first isolated in the fifties from an isolate of dirt in the jungles of Borneo by a missionary. It is a naturally occurring antibiotic made by the soil bacterium Actinobacteria. The name vancomycin comes from the word vanquish.  Initially it was used as a sort-of last resort for penicillinase-producing strains of Staphylococcus aureus.  Today, vancomycin is one of the most widely used antibiotics for the treatment of serious gram positive infections involving methicillin-resistant S. aureus (MRSA). Years ago, early use of vancomycin was associated with several different types of toxicities including infusion related effects (Red Man Syndrome), nephrotoxicity (kidney), and possible ototoxicity (damage to ears).  It was determined later that the majority of these adverse effects were due to the early formulations that contained impurities; however, by that time, its use was decreased with the development of other penicillin-type medicines like methicillin, oxacillin, and nafcillin).  Thanks to MRSA, Vancomycin is making a huge comeback, or has been since the early 1980s.

On a side note, Red Man Syndrome is not an allergic reaction.  This can be managed with a histamine blocker or slowing down the infusion.  Can't tell you how many times I have seen this listed as an allergy to vancomycin on someone's profile.

In monitoring Vancomycin, trough serum concentrations are the most accurate method.  Typically draw the trough level prior to the fourth dose (steady-state).  Keep trough levels above at least 10 mg/L to avoid development of resistance.  For a pathogen with an MIC of 1 mg/L, the minimum trough concentration would have to be at least 15 mg/L.  For complicated infections, the optimal trough concentrations are 15-20 mg/L to improve penetration, increase optimal serum concentrations, and improve clinical outcomes.

How to dose?  Dosing vancomycin is a bit of an art, but start at 15-20 mg/kg using actual body weight.  Many hospitals encourage a maximum dose of 2 grams.  Definitely adjust dose in renal dysfunction.

Creatinine Clearance(based on Cockcroft and Gault and not eGRF)	Dose*
>60 ml/min	Uncomplicated Infections: 10-15 mg/kg q12h1  Serious Infections: Consider loading dose of 25mg/kg IV x1, followed by 15-20 mg/kg q8-12h (45-60mg/kg/day divided q12h or q8h)2
40-60 ml/min	10-15 mg/kg q12h-q24h
20-40 ml/min	5-10 mg/kg q24h
10-20 ml/min	5-10 mg/kg q24h-q48h
<10 ml/min	10 - 15 mg/kg IV loading dose x1; redose according to serum levels
Hemodialysis	15-20 mg/kg load, then 500 mg IV post HD only
CVVH	10-15 mg/kg q24h

* round dose to 250mg, 500mg, 750mg, 1g, 1.25g, 1.5g, 1.75g or 2g (maximum: 2gm/dose)

Higher total daily doses of vancomycin have been associated with nephrotoxicity

¹ For patients with uncomplicated infections requiring vancomycin, trough levels of 10-15 mcg/ml are recommended.

² For patients with serious infections due to MRSA (central nervous system infections, endocarditis, ventilator-associated pneumonia, bacteremia or osteomyelitis) , trough levels of 15-20 mcg/ml are recommended.

Vancomycin troughs are not recommended in patients in whom anticipated duration of therapy is short (≤ 3 days)

Trough levels are recommended for routine monitoring (for intermittent hemodialysis, a pre-dialysis level should be drawn). Trough levels should be obtained within 30 minutes before 4^th dose of a new regimen or dosage change.

Once weekly monitoring is reasonable in patients with stable renal function and clinical status. (Data supporting safety or prolonged troughs of 15-20 mcg/ml is limited.)

There is a great app out there I recommend called Vancomycin ClinCalc Full.  The author also has a website called ClinCalc you can check out to see if the dosing matches how your particular program wants you to do it.

I don't earn a dime for that link either, I just enjoy finding quality programs to work more efficiently.

I love Dr. Walter Crittenden, PharmD MD "An Infections Disease Compendium:  A Persiflagers Guide" on the iPad as well.

One of my biggest pet-peeves is when I hear someone say, "Oh I have blown their kidneys!" in regards to one serum creatinine level coming back higher.  Hey, let's wait until 2-3 consecutive high serum creatinine concentrations (increase of 0.5 mg/dL or 150% increase from baseline, whichever is greater) after several days before making such a claim.  Seriously.

And the "Rants and Screeds" of Dr. Crittenden, "Vancomycin is a shitty drug; mostly static, toxic, lousy pharmacokinetics, penetrates poorly into all tissues.  When compared to beta lactams, it is always worse."

Gotta love that!

Fungal Meningitis and the End of Lackadaisical FDA Involvement in Compound Pharmacies

New England Compounding Center (NECC) is at the center of this quite horrific tragedy that has affected the lives of many with fourteen already dead. I cannot personally fathom such a loss over something so seemingly accidental. As a pharmacist my thoughts immediately go to sterile technique and the FDA's regulation of our industry. You see, the states oversee the pharmacies compounding and normally that should be enough. However, something went terribly wrong here. But what is coming out lately is the role of compounding pharmacies and how in this case, there was a grey area they were working in. Basically compound pharmacies can make patient specific medications, what is not allowed is these compounding pharmacies acting as manufacturing and bulk shipping repackaged medications without FDA oversight.

It's all about the dollar, but in this case many priceless lives have been lost.

There are two fungi involved: aspergillus and Exserohilum rostratum.

In the past, these pharmacies have been the heroes making things like bioidentical hormones and other specialty concoctions.

Under the FDA's definition, compounding pharmacies are supposed to mix drugs to order only on a specific patient in response to a prescription from a doctor. Under this definition NECC was not operating as a compounding pharmacy but as a large-scale production of a drug. The FDa should have stepped in before these lives were lost.

June 27 is National HIV Testing Day

HIV (human immunodeficiency virus) is the virus that causes AIDS. Today, in honor of National HIV Testing Day, the healthcare community encourages you to get tested for HIV. The only way to know if you have HIV is to get tested. Many people with HIV don’t have any symptoms. In the United States, 1 in 5 people living with HIV don't know they have it.

Even if you don’t feel sick, getting early treatment for HIV is important: early treatment can help you live a longer, healthier life.

Am I at risk for HIV?

HIV is spread through some of the body’s fluids, like blood, semen (cum), vaginal fluids, and breast milk. HIV is passed from one person to another by:

• Having unprotected sex (vaginal, anal, or oral) with a person who has HIV
• Sharing needles with someone who has HIV
• Breastfeeding, pregnancy, or childbirth if the mother has HIV
• Getting a blood transfusion that has HIV (very rare in the U.S.)

HIV testing is covered for many people under the Affordable Care Act, the health care reform law passed in 2010. Depending on your insurance plan, you may be able to get tested at no cost to you. Talk to your insurance provider.

Memorization, the Power of Mnemonics

Now that I have committed to the large mental task of taking on the BCPS exam, I'm finding memorization for the sake of memorization to be lacking. Rather than waste the moments I have studying repeating over and over what organisms doxycycline covers, I've started creating this microorganism world mentally that will connect all aspects through the use of mnemonics. Another technique I've debated is the use of songs. But creating songs still requires more memory time. Oh, and a different part of the brain.

Three things: association, memorization, and location. So, for example let's say that we want to memorize community acquired pneumonia (cap). I imagine a room full I healthy men wearing caps and their choices are a macrolide or doxycycline. To memorize the macrolide I imagine them with macro lenses (macrolide) and they are shooting pictures of dachshunds on cycles (doxycycline). They have no other illnesses going on, and the treatment is at least five days.

See the technique? Men wearing caps, no other underlying illnesses to interfere with shooting macro images of dachshunds on cycles.

You may never forget it! Or at least I hope I don't come October.

Google mind maps to gain more information about these techniques!