Treatment of Pseudomonas aeruginosa remains challenging, despite the availability ceftolozane-tazobactam. We report a treatment failure with ceftolozane-tazobactam salvage therapy for pneumonia complicated by lung abscess. Drug resistance, dose selection, and source control are possible contributing factors. Ceftolozane-tazobactam susceptibility testing should precede therapy and consideration should be given to dosing selection.

Under senare år har en särskilt hög resistensutveckling observerats hos gramnegativa bakterier inom familjen Enterobacteriaceae. Den främsta resistensmekanismen utgör produktion av så kallade "extended-spectrum β-lactamases" (ESBL) och särskilt oroväckande är karbapenemaser (ESBLCARBA) som har förmåga att bryta ner ett flertal olika grupper av β-laktamantibiotika. Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) har utforskats som metod för snabb detektion av karbapenemasaktivitet genom analys av nedbrytning av antibiotika. Syftet med denna studie var att utvärdera om MALDI-TOF MS kan användas som metod för att detektera enzymatisk nedbrytning av Ceftolozan/Tazobaktam samt att undersöka vilka enzymer som uppvisar nedbrytning av antibiotikan. Sju karbapenemasproducerande isolat och en β-laktamasnegativ kontrollstam användes i studien. Isolaten inkuberades 120 min respektive 270 min med antibiotika (1mg/ml) i en buffertlösning (0,08% ammoniumbikarbonat, pH 8). Efter centrifugering analyserades supernatanten med MALDI-TOF MS. Nedbrytning av Ceftolozan detekterades hos samtliga karbapenemasproducerande stammar, utom hos E. coli med NDM-1 produktion. Nedbrytningstoppar av Tazobaktam detekterades emellertid enbart hos stammar med OXA-48 och NDM-7 produktion. Tydligast nedbrytning sågs efter 120 min. För tydligare visualisering av nedbrytningstoppar bör metoden dock optimeras med avseende på matrix, buffert och antibiotikakoncentration. / In recent years, an alarming increase of antibiotic resistance has been observed in Gram-negative bacteria, classified in the family Enterobacteriaceae. The main resistance mechanism is the production of extended-spectrum β-lactamases (ESBL). Particularly worrisome is the production of carbapenemases (ESBLCARBA) due to their ability to hydrolyze a broad range of β-lactams. Recently, Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) has been investigated as a method for rapid detection of carbapenemase activity through observation of antibiotic degradation. The aim of this study was to investigate whether MALDI-TOF MS can be used as a method to detect degradation of Ceftolozane/Tazobactam as well as to examine which enzymes that possess the ability to hydrolyze the antibiotic. A total of seven carbapenemase-producing strains were used in the study. The experiment also included a β-lactamase-negative isolate as a negative control. The strains were incubated with antibiotic (1mg/ml) in a buffered solution (0,08% ammonium bicarbonate, pH 8) for 120 min and 270 min. The supernatant, after centrifugation, was analyzed by MALDI-TOF MS. All the carbapenemase-producing strains demonstrated hydrolysis of Ceftolozane, except for NDM-1 producing E. coli. However, mass peaks corresponding to the degradation of Tazobactam were only detected in strains producing OXA-48 and NDM-7. The degradation of Ceftolozane/Tazobactam was most apparent after 120 minutes. However, to better enable detection of mass peaks, further optimization is needed in regard to appropriate matrix, buffer and antibiotic concentration.