Empiric Antibiotics and SSRRH Antibiogram (Patel, 9/25/24)

 Many thanks to Omi Patel, PharmD and head of our SSRRH pharmacy for an excellent and important talk on Empiric Antibiotics and the SSRRH Antibiogram. A recording of her presentation is available HERE. 

My notes:

Empiric antibiotics should be chosen based on many different factors:

• patient characteristics (age, comorbidities, recent hospitalization, etc)
• site of infection
• pharmacokinetics
• evidence-based guidelines (e.g. IDSA, John's Hopkins, Sanford guide)
• facility specific guidelines (CPMC, UCSF)
• clinical pathways (most recent possible)
• local antibiogram (which is what this talk focused on)

At SSRRH, there is a system-wide order set that offers empiric antibiotic options based on site of infection. It is available under order sets. Do NOTE these are not specific to SSRRH, and our local antibiogram should be consulted if using these order sets.

As noted above, the hospital specific antibiogram is essential to good antibiotic stewardship. Omi pointed out that for bacteria for which we have less than 30 isolates, the data is less reliable and trends over time (i.e. looking back at old antibiograms) may be helpful in choosing the empiric treatment. You can see on the antibiogram below, the numbers in red reflect the number of isolates from 2023 of that particular bacteria. Reach out to the pharmacist to help you with this. The "30 isolate rule" is a National standard so applies to any antibiogram

Gram Negative Organisms at SSRRH

trends over time for Morganella at SSRRH

Last year, at SSRRH 64% of Gram Negative Organisms were E Coli. Other more commonly isolated organisms include Klebsiella, Pseudomonas, Proteus and Enterobacter.

For general medical patients, >85% susceptibility is considered adequate for empiric antibiotics.

For ICU patients, the higher the better, >90% susceptibility is preferred.

Empiric UTI Treatment

In 2023, SSRRH changed to using Cefoxitin, a second generation cephalosporin, as our first line for empiric parenteral UTI treatment.

Of note, our current rates of susceptibility of E Coli to ciprofloxacin (80%), levofloxacin (77%) and Bactrim (79%) mean that we should NOT be using them for empiric treatment for UTI.

Omi reminded us of a few common clinical circumstances:

• Despite common practice, ceftriaxone does not concentrate well in the urine as cefoxitin. Ceftriaxone should not be first line for UTI treatment
• Once culture results return, use the specific data to drive antibiotic treatment moving forward
• If a patient has had a recent history-- meaning in the last 120 days) of infection at the same site, use that information (and NOT the antibiogram) to drive your empiric antibiotic choice
• ESBL is a form of resistance that presents in gram negative bacteria. 
• The CTX-M gene (aka Ceftriaxone resistance) is a surrogate marker for ESBL 
• Sutter labs will not specifically report out an ESBL organism, so LOOK for ceftriaxone resistance as a surrogate marker for ESBL organisms
• If you suspect an ESBL organism, do NOT use Zosyn, any cephalosporin for empiric treatment. Your best choice is a carbapenem

• For pseudomonas aeruginosa, the only oral abx for this organism locally is ciprofloxacin, and based on 2023 antibiogram, it is currently only 83% sensitive
• do NOT use levofloxacin (77% sensitive)

Empiric Staph Aureus 

• MRSA resistance to clindamycin has been consistently high since 2017 (around 59%)
• do NOT use clindamycin for MRSA coverage
• Resistance to TMP-SMX is increasing in Santa Rosa (>16% resistance rate)
• Doxycycline sensitivity (currently 95%) is significantly higher than tetracycline (68%).
• Tetracycline is NOT a good surrogate marker for doxy against MRSA. Therefore, susceptibilities should be reported separately.
• Doxycycline is a good local choice for empiric MRSA coverage

Empiric Group B Strep (GBS)

• Local GBS is resistant to clindamycin 50% of the time, GAS is resistant 25% of the time
• Clindamycin should never be used to empirically cover GBS in a pregnant woman without sensitivities 
• Unless sensitivity is known, linezolid is preferred over clindamycin to inhibit toxin production (usually just 3 days duration)

Restricted Antibiotics

At SSRRH, certain antibiotics are restricted to ID approval with the intention of preventing misuse/overuse and preserving susceptibility over time. This technique has proven successful in limiting our local resistance. The restricted antibiotics include:

Empiric Antibiotics and Antibiotic Stewardship (Green & Patel 10/18/2023)

LINK to a recording of the presentation is available HERE. 

***

It is with deep gratitude and great joy that I can say proudly that we did Grand Rounds in a room together at SSRRH for the first time since February 2020! It has been over three years since we gathered today in Conference Rooms A/B at SSRRH, and while we have had some magnificent zoom talks together in the interim, it felt both deliciously indulgent and so very right to be sitting together fighting the AV equipment. Together. We had 22 esteemed live attendees, and another 31 online. And that was even without serving breakfast (which will be available starting next week). A guest appearance from our very own Dr. Rick Flinders was icing on the cake.

And I haven't even started talking about the presentation yet -- which was excellent.

Many thanks to our antibiotic experts, Dr. Gary Green and Pharmacist Omi Patel, for both inspiring the reunion and giving an excellent opening talk on Empiric Antibiotics and Antibiotic Stewardship at SSRRH. The recording will be available shortly and the empiric antibiotic guidelines and the antibiogram are both available on the SSRRH intranet.

As for my notes:

We are so lucky to have the camaraderie and support of our pharmacists at SSRRH for improved antibiotic management of hospitalized patients. They are truly partners and educators for our clinicians.

Antibiotic stewardship program includes several important pharmacy driven protocols. These evidence-based pharmacy driven protocols include: 

• Renal adjustments of antibiotics
• Pharmacokinetic review of vancomycin and aminoglycoside (i.e. vancomycin dosing "per pharmacy protocol")
• Automatic stops for medications like azithromycin and oseltamivir (when indicated)
• Transitioning from IV to PO antibiotics
• Extended infusions of beta lactam antibiotics (meropenem, cefepime, cefazolin, and zosyn)
• Probiotics for floor patients at high risk for C Diff colitis

Omi Patel reviewed the importance of these protocols and gave us a preview of an upcoming QT monitoring protocol as well. 

Then Dr. Gary Green then filled us in on highlights of the ASP 2022-2023 Empiric Antibiotic Guidelines

These include:

Skin and Soft Tissue Infections (SSTI): a review on clinical assessment of cellulitis, most commonly strep vs. staph infections, including a reminder that staph infections tend to have a more demarcated (i.e. easy to draw) line between infected and uninfected tissue compared to strep infections, which tend to have a more "feathered edge". Don't forget that strep is also famous for causing lymphangitis ("streaking and tenderness" above the level of the actual cellulitis).

When treating SSTI, remember, "Cefazolin is your friend." -Gary Green, MD

Bullae are common later in SSTI and should not be cultured or removed (creating a wound)

If there is concern for toxin-mediated cellulitis (e.g. early bullae, <24 hours from cellulitis onset), consider the addition of clindamycin as an anti-toxin medication. Reminder that clindamycin works on ribosomes, which gives it its anti-toxin properties.

Vancomycin, while bactericidal, is still a very slowwwwwwwwwwwww bactericidal drug, and Dr. Green reports lots of failures in treatment of SSTI. Don't use it if you don't need it.

In the setting of fluctuance (carbuncles or furuncles), you should definitely consider ca-MRSA as the likely culprit. Cultures are imperative, and consider Septra or doxy as first line oral outpatient abx. Dalbavancin ER is sometimes used in the ED for patients for whom compliance can be challenging.

slide c/o Dr. Green, Omi Patel, PharmD

(Note that Ceftaroline, a 4th gen, is the first cephalosporin with activity against MRSA). 

Diabetic foot infections are a totally different thing than cellulitis and should NOT be misdiagnosed. They are often characterized by a diabetic foot ulcer (and can include osteomyelitis). Outpatient treatment for diabetic foot infections first line are Augmentin and/or moxifloxacin. If you are concerned about MRSA, you could add septra or doxy to those first-line drugs. Inpatient treatment for diabetic foot infections are a start with vanc/zosyn, but culture quickly and drop vanc as soon as culture does not reveal MRSA. Remember the combination of v/z is nephrotoxic and should only be continued if clinically indicated. 

Additionally, do not use abx to treat lower extremity venous stasis, which often presents with dependent rubor (redness). If you believe this is erythema of gravity, lift the legs above the level of the heart to see if rubor improves. Venous stasis is chronic and can present with some mild tenderness and even mild warmth. Do not treat in the absence of active infection. 

Diverticulitis and intra-abdominal infections

outpatient empiric abx: Augmentin OR ciprofloxacin plus metronidazole

inpatient empiric abx: Pip/taz (i.e. Zosyn) or ceftriaxone plus metronidazole . The Zosyn should be delivered as an extended infusion whenever possible. Ceftriaxone plus metro does miss enterococcus, but, as Dr. Green said "enterococcus is generally the bridesmaid and never the bride" -- meaning, it may  be present but is often not the cause of the infection. 

Pancreatitis should NOT be treated with abx. Unless it is necrotizing. In rare cases of necrotizing pancreatitis, the drug of choice (with good evidence for improved outcomes) is meropenem. 

UTI is where the largest system-wide change in empiric abx comes in. 

First off, Asymptomatic bacteriuria (AB) is too often in appropriately treated with abx. Dr. Green said that 50% of inappropriate abx are attributed to treatment for asymptomatic bacteriuria. The bladder is transiently colonized and the presence of bacteria on culture does not indicate infection in the absence of symptoms. So, in other words, do NOT treat AB with antibiotics. The exceptions are: 1) pregnant patients and 2) transplant patients. 

Based on our local antibiogram, nitrofurantoin (aka Macrobid) is the empiric antibiotic of choice for uncomplicated outpatient UTI. Additional options include TMP/SMX and ciprofloxacin, though there is more resistance to both of these abx than there is to Macrobid. The one downside to Macrobid, we al know, is that it does not have good renal penetration and should not be used for pyelonephritis.

In complicated UTI (defined as neurogenic bladder, Foley catheter present, suprapubic catheter, and/or recurrent UTI), 

Okay, now for complicated UTI and/or pyelonephritis in hospitalized patients. The new drug of choice is Cefoxitin (2gm q6 hours). This is for two reasons: 1) Ceftriaxone has never been a great UTI drug, it is hepatically metabolize and not renally cleared). 2) Our local sensitivities for e coli are down to 88% at SSRRH. Once under 90%, it is no longer a reliable empiric abx. 

Other drugs to consider for complicated UTI are aztreonam and cipro IV. 

A note on ceftriaxone: While we should no longer be using ceftriaxone for pyelonephritis or complicated UTI in hospitalized patients for the above reasons, Ceftriaxone (2gm, per Dr. Green 1gm is a homeopathic dose) remains an excellent choice for both community acquired pneumonia and gonorrhea. 

And finally, 

Community acquired pneumonia. Empiric guidelines still recommend ceftriaxone plus either azithro or doxycycline. Both Dr. Green and I agree that doxycycline is probably a better choice in most patients due to the QT prolongation and increased CV mortality that occur with azithromycin.

Another reasonable option for CAP. is levofloxacin. 

For Aspiration Pneumonia, SSRRH and Dr. Green's empiric guidelines differ slightly from the IDSA on aspiration pneumonia, recommending Zosyn, particularly in frail patients with teeth (pearl: if patients have no teeth, you don not have to worry about anaerobes). Hospital acquired and Ventilator associated PNA should get ID involved, abx include pip/tazo and/or cefepime.