Dear Raluca,

Please read the following text:

The oral options available for the treatment of cUTI caused by ESBL or AmpC-producing bacteria are limited, particularly if susceptibility testing indicates concurrent resistance to trimethoprim and quinolones. Most organisms remain susceptible to nitrofurantoin; however, this agent is licensed for lower UTIs only and the authors’ personal experience has shown that resistance may develop on treatment. One alternative is an agent used more widely in the rest of Europe—fosfomycin. Fosfomycin is approved by the Food and Drug Administration in the United States for treatment of uncomplicated lower UTI and single-dose therapy (3 g oral powder) was found to be equivalent to a 7 day course of norfloxacin in a randomized open-label study. For treatment of cUTI, dose regimens of 3 g every 2–3 days for up to 21 days have been used but due to limited systemic absorption, fosfomycin should not be used for pyelonephritis or severe urinary sepsis. Fosfomycin is licensed in the UK but a licensed formulation is not currently marketed. Supplies are available from pharmaceutical importers but a delay of 24–48 h for a community pharmacy to obtain stock limits the usefulness of this agent in a primary care setting.

Failures have been reported when pivmecillinam has been used alone to treat infections caused by ESBL-producing organisms and in vitro studies have shown significantly raised MICs at a higher inoculum of 106cfu/spot. However, there is evidence that the addition of clavulanic acid results in a decrease in MIC bringing it down from an intermediate/resistant range to within the susceptible range (the modal value was reduced from 8–16 to 0.03–0.06 mg/L). A combination of agents containing clavulanic acid (for example co-amoxiclav) with other readily available extended-spectrum oral antibiotics that resist hydrolysis by common β-lactamases, such as pivmecillinam, cefixime or cefpodoxime, has been used to treat UTIs caused by CTX-M ESBL-producing E. coli. These combinations are unlicensed and reports of such use in the literature are rare. They are not effective against AmpC-producing Enterobacteriaceae as the clavulanate induces the production of AmpC enzymes, which attack the cephalosporin. Combinations of cefepime or cefpirome (both are in intravenous form only and not available in the UK) with clavulanate could be considered, as these agents are more stable to AmpC enzymes. In summary, these combinations should not be used as empirical therapy but could be considered once the organism and type of resistance are known.

It may be possible to use intravenous agents that can be given once a day such as gentamicin (also suitable for intramuscular injection) and ertapenem on an outpatient basis. Gentamicin is contraindicated in significant renal impairment, which is more common in the elderly, and regular monitoring of pre-dose serum concentrations is required to assess further dosing. When infection is more severe  and the patient possibly has bacteraemia, intravenous therapy should be given. The choice of antibiotic will depend on the severity and site of the infection and whether the susceptibility pattern of the organism is known. A treatment strategy should be based on the local susceptibility pattern, so where the local pathogens remain susceptible, for instance in areas where CTX-M ESBL-producing E. coli is predominant, gentamicin may be used as empirical therapy—in combination with other agents to treat a severe infection. Amikacin has been used as an alternative where gentamicin-resistant isolates remain susceptible to it.

This text was taken from a publication entitled " Complicated urinary tract infections: practical solutions for the treatment of multiresistant Gram-negative bacteria" by Ann Pallett and Kieran Hand published in J. Antimicrob. Chemother. (2010) 65 (suppl 3): iii25-iii33.

http://jac.oxfordjournals.org/content/65/suppl_3/iii25.full

Hoping this will be helpful,

Rafik

Dear Mr. Karaman,

Thank you for your rapid and documented answer. Please, let me give you more information on this subject. An initial analyse of the strain resistance has shown sensibility to Amikacin, Imipenem, Meropenem, Piperacilinum+Tazobactamum and resistance to Amoxicilin/Clavulanic Acid, Ampicilin, Cefotaxime, Cefuroxime, Ciprofloxacinum, Fosfomycin, Gentamicin, Levofloxacin, Netilmicin, Nitrofurantoine, Norfloxacinum, Tetracycline, Trimetoprimum/ Sulfamethoxazolum .

After a first therapeutical attempt with Meropenem the antibiogram was modified as follows:

-          Sensibility: Amikacin, Cefoxitin

-          Intermediate sensibility:  Imipenem, Meropenem

-          Resistance: Amoxicilin/Clavulanic Acid, Ampicilin, Cefaclor, Cefotaxime, Ceftriaxon, Cefuroxime, Gentamicin, Levofloxacin, Norfloxacin, Trimetoprimum/ Sulfamethoxazolum.

Raluca

What happened to piperacillin/tazobactam sensitivity?

The use of carbapenems agains these urinary pathogens is risky, as you can see with the most recent antibiogram.

The first step when we face against multiresistant urinary gram negative bacteria is to separate infection from colonization. In case of infection, we must define if it's confined to lower urinary tract (aka cystitis) or if we have bacteriemia. In cystitis, due to an extraordinary multiplication of urinary concentrations, even in vitro resistant antibiotics may work in vivo. It happens for TMP-SMX, nitrofurantoine and norfloxacin.

For urinary sepsis our last weapon in Portugal is IV colistin. Off label, in my hospital, we use sometimes intravesical colistin: no systemic side effects and good results in eradicating MR Klebsiella, providing no sepsis is suspected.

Dear Mr. Carvalho,

Thank you very much. Very interesting answer. More than that a new in deep analyse revealed, also, the presence of MR Acinetobacter. 

Once again, thank you very much.

Raluca