IDSA’s Emerging Infections Network



IDSA Emerging Infections Network Preliminary Report for

Periodic Query on “Persistent MRSA Bacteremia”

• 891 physicians received queries, and 454 (51%) responded as of 3/15/05;

4 respondents were unable to provide unique or relevant data [n = 450]

| |# EIN Members Responding |

|Region | |

|New England |33 |

|Mid Atlantic |68 |

|EN Central |61 |

|WN Central |26 |

|S Atlantic |92 |

|ES Central |24 |

|WS Central |40 |

|Mountain |25 |

|Pacific |74 |

|US Territories |3 |

|Canada |4 |

|Total |450 |

• Question One: 163 (36%) EIN respondents reported seeing an increased number of patients with persistent (>7 days) MRSA bacteremia on vancomycin therapy in the last year (2004). See below for regional breakdown.

• Question Two: 281 (62%) EIN respondents indicated that they had seen approximately 1143 cases of persistent (>7 days) MRSA bacteremia on vancomycin therapy in the last year (2004). See below for regional breakdown.

| |# EIN Members Seeing ( # of Patients with Persistent |# EIN Members [Approximate # of Cases] Seeing |

|Region |(>7 days) MRSA Bacteremia on Vancomycin |Persistent (>7 days) MRSA Bacteremia on Vancomycin |

|New England |13 |18 [67] |

|Mid Atlantic |27 |44 [202] |

|EN Central |21 |40 [166] |

|WN Central |10 |19 [70] |

|S Atlantic |37 |62 [226] |

|ES Central |6 |11 [44] |

|WS Central |15 |25 [142] |

|Mountain |8 |14 [32] |

|Pacific |25 |44 [185] |

|US Territories |- |3 [5] |

|Canada |1 |1 [4] |

|Total |163 |281 [1143] |

• Question Three: EIN respondents reported that when confronted with a case of persistent (>7 days) MRSA bacteremia, they use the minimal inhibitory concentration (MIC) of vancomycin for MRSA to guide patient management as follows:

110 (24%) Always

107 (24%) Usually

69 (15%) Sometimes

53 (12%) Occasionally

65 (14%) Never

46 (10%) Unanswered

• Question Four: 353 (78%) EIN respondents indicated that their microbiology laboratory provides MIC data for MRSA clinical isolates. Of the 423 EIN respondents eligible to complete the 2nd part of this question, 169 (40%) EIN respondents indicated that they receive this information routinely while 120 (28%) EIN respondents indicated that they only receive it by request.

Case Scenario: 57 y/o man with complicated diabetes mellitus hospitalized for febrile illness and found to have MRSA bacteremia. No source identified and patient remains febrile and bacteremic despite 7 days of vancomycin therapy (15 mg/kg BID) -- trough levels ranging from 8-10 (g/ml. Negative transthoracic ECHO, no hardware or catheters, and no evidence of abscess. As you continue to search for a focus of infection, the lab calls and tells you the MIC for vancomycin is, which is considered susceptible and a common result for your lab.

• Question Five: EIN respondents reported that they would treat the above patient as follows on next page:

• Question Six: EIN respondents indicated that they would treat the same patient but now the MIC for vancomycin is 4 (g/ml, which is still susceptible but unusually high for your lab as follows on next page:

| |Question #5 (MIC 2 (g/ml) |Question #6 (MIC 4 (g/ml) |

|OPTION 1: |12 |1 |

|Continue vancomycin at current dosage | | |

|OPTION 2: |26 |7 |

|Continue vancomycin alone, but ( dose to achieve peak serum levels (50 (g/ml | | |

|OPTION 3: |317 |126 |

|Continue vancomycin but also add | | |

|gentamicin |153 |56 |

|linezolid |16 |22 |

|rifampin |241 |86 |

|daptomycin |15 |19 |

|synercid( |6 |5 |

|OPTION 4: |83 |302 |

|Discontinue vancomycin and switch to one or more of the following agents | | |

|gentamicin |13 |32 |

|linezolid |46 |158 |

|rifampin |21 |60 |

|daptomycin |54 |170 |

|synercid( |9 |20 |

• Additional Comments on Survey Topic:

PA -- Aminoglycosides are too toxic to use long-term in these pts. Synercid - vancomycin is best combination available at present - based on microbiological information

CO -- Some colleagues add dapto to vanco - mostly for medicolegal reasons

TX -- We have added oxacillin to vancomycin (Antimicrob Agents Chemother, 2000;44:1394) with rapid (?coincidental?) results.

PA -- Had 2 cases just this past month & one pt also failed linezolid & is on daptomycin now. Lab stated S to linezolid. No deep focus found.

FL -- Most of our MRSA are still clinda S

NJ -- I would request MBC's and time kill curves for the 2nd isolate. Would also undertake additional search for the probable explanation i.e., an occult sequestrum or nidus of infection.

NC -- For the above patient, I might do a tagged WBC scan to look for an occult abscess. If rifampin sensitive, I probably would also add it. Regarding ORSA without treatment response or with high vancomycin MIC, I would consider ordering a MBC as well.

NY -- We would consider adding linezolid in synergy if rifampin does not do the trick

NY -- I have used Daptomycin in two patients who developed reactions to vancomycin (allergy or leukopenia). Both did well and have not been readmitted yet in the last month.

FL -- In all cases of MRSA bacteremia, I routinely aim for a trough of 15-25. This is the first thing I would have done with both of the cases above.

NY -- I would try to keep trough levels around 20. I do not use high peak levels to adjust dosing.

LA -- Most of vancomycin "failures" (especially in ESRD or OPAT patients) is due to inappropriate serum levels.

NM -- There should be an option for both increasing the dose of vanco and adding other agents

IL -- we saw 2 cases of 6-day bacteremia in 2003 and 3 cases of ultralong bacteremia (64, 41, 240 days) in 2004. The ultralong cases usually relate to relapses of foreign body s/p infection. Our "maximal" MIC of vanco so far = 3

TX -- My addition of drugs in Q6 would be sequential - 1st gentamicin and rifampin, 2nd daptomycin if bacteremia continued.

OH -- I would also do U/S of all deep veins to r/o septic thrombophlebitis which would mandate anticoagulation.

CA -- If a patient has a true vanco allergy, would you choose dapto or linezolid? I think there is rabbit data for both which look ok.

NY -- Would both increase vanco to peak of 50 and trough of 15 and add both gentamicin and rifampin.

TX -- For persistent bacteremia, would do TEE as well.

MO -- Have seen prolonged bacteremia but not >7 days. Successfully used linezolid also depending on source, etc.

MD -- My management would be more aggressive if the patient were deteriorating clinically, and I would certainly be aggressive in looking for the source of the apparent bacteremia.

CA -- I wouldn't actually wait for 7 days of bacteremia (regardless of whether there was a source) - I would have added the gent and rif very early in the course - so by day 7 I would actually be switching drugs

OH -- We've tried lots of combos. None are uniformly successful

OH -- Have had 2 recent patients in whom we could not clear MRSA bacteremia despite vanco/gent/rif/dapto. MIC 2.0 to vanco, lab screens all MRSA with vanco agar, and e-test done to exclude VISA/VRSA still sensitive by usual criteria.

FL -- I have tried vancomycin + gentamicin and it did not work (with good blood levels and susceptible strain). Now, I switch rapidly and sometimes I use up to 3 drugs. Results have been satisfactory.

MO -- I would start this pt on gent sooner than d 7.

OR -- In the case above it is critical to know if MRSA is sensitive to f'quinolones; tmp/sulfa; clinda

TX -- I do not use peak serum levels of vancomycin for monitoring. Trough levels are more helpful and recs are to keep trough levels in range of 10-15 mcg/ml for serious infections. This was not an option mentioned above.

WI -- I don't like the trough levels for your patient - for bacteremia I aim for 10-15.

NY -- How effective is linezolid & synercid compared to vancomycin?

NY -- Had one case of septic arthritis (knee) w/MRSA in a dialysis pt (no hardware) - couldn't clear w/vancomycin/rifampin/genta - changed to vancomycin/daptomycin - infection cleared.

WA -- For question 5: Rather, I would push the trough level high - try to keep trough >=20. Also, you did not reference J Clin Micro 2004 42:2398 - which did not specifically look at prolonged bacteremia, but report correlation between different vanco MICs and outcomes.

CA -- I would have liked other options for this form. I would push the dose of vanco to higher peaks and troughs regardless for MRSA bacteremia, and use gent often. We worry about possible antagonism with rif, although this isn't common, and will use it also in a pinch. For failures of this approach, we've used linezolid +/- daptomycin to good effect.

UT -- I believe that many of us would use more than 1 option listed above. For example with persistant MRSA or CONS we will increase vanco trough levels to 20 and add either gent or rifampin based on sensitivity. If this does not work then linezolid is added. I am a pediatrician and have only used daptomycin 1 time, for a preterm neonate with 19 days of positive blood cultures with MRSA who had failed vancomycin in combination with gent, rifampin, and linezolid. The patient cleared the bloodstream after the addition of daptomycin, but the drug had to be stopped because of increasing liver enzymes. In our area, persistent CONS in the preterm infant is a more common problem than persistent MRSA. These infections are with CONS with vanco MIC of 2-4 and most are gent resistant. These CONS infections often fail high dose vancomycin in combination with gent or rifampin and linezolid is used as rescue therapy.

TX -- We add Synercid to vancomycin in the above scenarios as our first line cloice, based on a small amount of clinical and animal data. We find, however, that a significant minority of our patients do not tolerate Synercid. For those patients we either switch to daptomycin alone or add daptomycin to vancomycin. There is more data emerging that an organism with a vanomycin MIC of ?1 is not truly "susceptible" to vancomycin.

CA -- Your questionnaire did not offer enough flexibility for complete answers. Another option, especially for the 4mics/ml isolate, is to to ETest or send it to reference lab. The 3d VRSA strain in MMWR had Microscan MIC of 4, but 256 by ETest, and 64 by broth dilution @ CDC. One could also quibble about sensitivity of TTE vs TEE in pt with no source. If negative TTE means absolutely normal that might be reassuring, but if just negative for vegetation leaves more room for false negative. Another issue: virtually ALL of our MRSA is CA-MRSA, and is sensitive to doxycycline, clinda, & trim/sulfa. Your questionnaire might get interesting results if those options were offered. Overall, I feel vanco is an inferior antibiotic....

AZ -- About 40% of our MRSA isolates are at MIC of 2. 57% of our Staph aureus bacteremias are MRSA. We had 241 patients with Staph aureus bacteremia in 2004. I am looking forward to seeing the results of bacteremia/endocarditis data using daptomycin. I suspect that it is much better than vanco. Vanco troughs in serious infection should probably be no less than 20. I have never understood how useful rifampin is in MRSA. Suspect that it gets used mostly to make “the clinician feel better.”

MN -- I have a problem with being presented with a limited set of options, none of which may be what I'd do. How am I supposed to answer such a question? For example, in scenario #1, I'd push the vanco dose, but to increase the trough, not the peak, plus would add other drugs.

NC -- As Pediatric ID, the scenario presented is different, but my reaction is the same. The first and second isolates I would ask the lab to do a full MIC by an alternate method (our lab routinely does it on a SA isolate with a Vanc MIC of 4 per CDC guidelines), as we do only breakpoints with Bactec plates. We have linezolid MIC done routinely on SA as well, however our micro lab director “suppresses” these results so that linezolid is not used “routinely.” He also does this with a few other antibiotics on SA, like fluoroquinolones, tetracycline, and Synercid®. I think this is a smart move. Daptomycin is not on our panel. We know we can go to the lab to get these MIC results, so for ID it is not a problem. As a note, often by adding the second (or third) drug to vancomycin usually eliminates the persistent bacteremia within 48 hours for us. I guess this means we are fortunate.

MA -- I have added rif in such cases - but am reluctant to do until blood cultures are sterile. Would do tee, bone imaging, ct scans at this point.

NC -- I would be curious to know if the general consensus is that daptomycin, with better in vitro killing data than any other anti-staphlococci agents, may turn out to be the drug of choice in treating staph aureus bacteremia (I realize that clinical data is pending).

MN -- I would also evaluate a patient with persistent bacteremia for the presence of septic thrombophlebitis. I've had at least one case of a woman with septic central vein thrombosis who cleared her bacteremia only after initiation of therapeutic heparin. Also, I would consider having the isolate checked for in vitro susceptibility to linezolid, rifampin, daptomycin and synercid.

BC -- Do not like above scenarios. Firstly, I usually use vancomycin if I have no alternatives, but routinely have troughs of ~ 20. Secondly, sometimes MRSA are susceptible to other drugs with which we have considerable experience (e.g. TMP-SMX, cipro, rif, fusidic acid) and I will add at least one of these to vancomycin routinely in these patients if they are susceptible. IF the isolate is susceptible to 2 or more of these, particularly if doing poorly on vanco, would consider using them in combination without vancomycin, in preference to use of linezolid or synercid which I consider relatively poor antimicrobials and not major improvements over vancomycin, which in itself I consider a not very potent antimicrobial. I have no personal experience with daptomycin. I ignored the gentamicin option because I do not recall ever having an MRSA strain resistant to rifampin and sensitive to gentamicin, and I prefer to use rifampin to avoid the nephrotoxic vanco-genta combination in a setting where its use would be for a minimum of many weeks. I hasten to add that all this experience is anecdotal.

KY -- For the past 15 years, I have recommended keeping vanc trough levels above 12 ug/ml. This is based on my in vitro work: Greenberg, R.N. and Benes, C. 1990. Results of Time Kill Studies with Vancomycin, Teicoplanin and Oxacillin against Staphylococcus aureus. J Infect Dis 161:1036-1037. Greenberg, R.N. Treatment of Bone, Joint and Vascular-Access Associated Gram-Positive Infections with Teicoplanin. 1990. Antimicrob Agents Chemother 34:2392-2397.

ND -- Over the last 14 years I have consistently used rifampin and gentamicin in combination for all staph aureus septicemias in the sicker patients. I have had no case where bacteremias have lasted more than 48 hours in community acquired, or hospital acquired cases.

NC -- As a side light, most non-ID folks do not use and are unaware of how to use MIC’s properly, so although they are reported out at this time our micro lab director is trying to get the actual MIC’s from being reported routinely, instead changing to a strictly Sensitive/Resistant report.

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