A 70 year female admitted to the ICU with UTI.
Report: Isolate- Serratia marcescens
Susceptibility report:
Aztreonam- resistant
Cefazolin- resistant
Cefotaxime- resistant
Ceftriaxone- resistant
Cefepime- MIC 4 microgm/ml
Cefotetan- resistant
Piperacillin/tazobactam- resistant
Imipenem- MIC less than 1 microgm/ml
If the isolate identification is accurate then Serratia are known to have natural resistance to BLactams in general and also first generation B-glycans.
The usual route of post definite Dx is Aminoglycoside or Quinolones but considering the age of the patient and other drug interaction which the patient might be taking an informed decision/choice has to be made.
Ref: http://emedicine.medscape.com/article/228495-medication
as a disclaimer I would like to add that I am not a clinician I am trying to answer this question as a molecular microbiologist.
Fosfomycin antibiotic is the best as recommended by Clinical Laboratory Standards Institute for UTI
AmpC B-lactamase is mechanism of resistant in this case because organisms expressing AmpCs confer high level resistance to many β-lactam agents including the third-generation cephalosporins and cephamycins (cefoxitin and cefotetan). Fourth-generation cephalosporins (cefepime) and carbapenems still have good activity against these enzymes. However, unlike ESBLs, AmpC β-lactamases are not inhibited by the commonly used inhibitors such as clavulanic acid, sulbactam, and tazobactam
Hi. I consider that in this case we've got a mix of resistance mechanisms. At first place, there is not only an stably derepressed Amp-C, there is an hyper-production of AmpC that explain the resistance to third-generation cephalosporins; I think you can't rule out the presence of ESBL because there are resistance to aztreonam and High MIC in cefepime. Taking account that the patient has an UTI and deserves treatment in ICU, my choice is a carbapenem, meropenem, and when she gets better, I would finish the treatment with ertapenem in her house.
Disclaimer, I am a microbiologist not a medic so therapy recommendations are purely based on the antibiogram you have shared.
Most likely AmpC producer, treat with a carbapenem, fosfomycin, ciprofloxacin or gentamicin. If using a carbapenem especially ertapenem then watch out for outer membrane loss mutations as combined with the AmpC you could get resistance to this class of antibiotics.
To phenotypicaly test for AmpC perform synergy testing with 3rd gen ceph and cloxacillin. See the attached link for a presentation from David Livermore for more info on synergy testing.
http://bsac.org.uk/wp-content/uploads/2012/02/Detecting_AmpC__ESBL_pruned.ppt
Resistance is genetic adaptability against any drug or chemical in bacteria, fungi, virus, protozoans or any other microbe. In resistance mechanism a microbe develop enzymatic scissors or enzymatic type I system, and type II system. These system after identification of drug catabolize completely and simplify its functional groups to an inactive molecule. All such resistance is developed due to induction effect or mutations inside genes that finally develop resistance. In case of isolates they form drug resistant mutant variants when they are exposed to all epigenetic factors or compounds, hence, there remains a possibility that to catabolize any new drug a new mutation will come, that naturally provide resistance through gene level selection in all clinical isolates. You will astonish even in drugs in storage, if they are liquid once open for use, if bacteria or virus find entry, it start working against it. This is a great challenge to the science. As the intensity or potential of drug is increased by adding new antimicrobial drugs, newer or latest mutations occur which again working against the drug and microbes get resistance in a very short span of time.
There is no drug of choice for avoiding resistance, but plant extracts or mixtures of herbs can fight against microbial resistance, because, it will become very difficult to microbes to develop resistance against hundreds of active components.
Having been a clinical pharmacist in an ICU I can say we would initially treat this with Meropenem 2g TDS (dependent on renal function) AND concurrent gentamicin 5mg/kg depending on levels. If there was concern regarding gentamicin resistance, Amikacin would be next line.
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