A 63-year-old man presented at the ICU for septic shock originating from a diabetic foot related ulcer. His medical history shows obesity, uncontrolled type 2 diabetes, cardiac ischemic disease, disseminated gout arthritis. Stating allergy to penicillin, he received empiric antibiotic therapy with amikacin, aztreonam and clindamycin. With the recognition of S. aureus bacteremia, treatment was altered to vancomycin and later oxacillin. Antimicrobial susceptibility testing (AST) included mainly Minimal Inhibitory Concentration (MIC) determination and in rare cases disc diffusion method and AST always follows EUCAST guidelines and breakpoints. An ESBL Klebsiella pneumoniae, an oxacillin-sensitive S. aureus (MSSA) and a multi-sensitive Pseudomonas aeruginosa were recovered from the wound. At day 7, he underwent surgical debridement for a lower limb gangrene and received ceftazidime. On day 10, he developed a central line-associated blood stream infection (CLABSI) due to an ESBL C. freundii associated with a MSSA and received meropenem. On day 24, he developed a CLABSI due to an ESBL K. pneumoniae (ceftazidime-avibactam susceptible (S), colistin resistant (R), cefiderocol susceptible) and was treated with ceftazidime-avibactam. At day 23, oxacillin was switched to cotrimoxazole to complete a 6-week therapy for lower limb osteomyelitis. On day 26, an XDR P. aeruginosa grew from his sputum. This P. aeruginosa is a chronic colonizer in our ICUs and expresses a class B VIM metallo β-lactamase, retaining sensitivity only to colistin. Ten days later, he developed a new bacteremia due to an ESBL K. pneumoniae (meropenem Intermediate (i), cefiderocol S), recovered from multiple sites including sputum and urines. At the same time, he developed a bacteremia with B. thetaiotaomicron, originating from a complicated ischemic pancreatitis, treated by a new cure of meropenem. On day 45, blood cultures grew K. pneumoniae, meropenem I, cefiderocol S. High doses meropenem and amikacin were started. Abdominal CT scan revealed a para-duodenal pancreatic collection. On day 51, endoscopic retrograde cholangiopancreatography was performed, and pancreatic pus revealed the XDR Pseudomonas aeruginosa, susceptible to colistin and cefiderocol. On day 51, colistin plus meropenem were started and cefiderocol was requested on a compassionate basis. On day 54, treatment was switched to cefiderocol 2 g Q8h (6 weeks) infused over 3 hours plus metronidazole 500 mg TID (2 weeks). Clinical and biological evolution were favorable and cefiderocol was stopped after 6 weeks. Cefiderocol was well tolerated and there was no treatment-related side effect.
Patient was transferred to rehabilitation unit where he developed an ischial eschar. On day 128, from a swab of the eschar grew an XDR P. aeruginosa with phenotypic resistance to cefiderocol.. In agreement with the patient, his wife and a medical committee, further ICU admission was banned to prevent the spread of this P. aeruginosa strain in our wards. Strict prevention control measures were re-enforced.
The strain was sent to the Belgian National Reference Laboratory for Resistant Strains and to the International Health Management Associates Inc in US (IHMA, Reference lab for Shionogi). Cefiderocol resistance was confirmed (MIC: 8 µg/ml) and a GES β-lactamase was identified. Additionally, our patient developed a right ankle arthritis due to an ESBL Citrobacter koseri. The C. koseri was also confirmed cefiderocol resistant (MIC: 16 µg/ml). A CTX-M group 9 type class A β-lactamase and a class D OXA-1 oxacillinase were identified. C. koseri retained susceptibility to ciprofloxacin and the patient was treated with ciprofloxacin for 6 weeks.
On day 224, the patient developed a hospital-associated pneumonia. He received ceftriaxone for two days. XDR P. aeruginosa was identified, and the patient was put on colistin plus meropenem. He died after 230 days of hospitalization. The patient spent 158 days on antibiotics (among which 42 days on cefiderocol) during his 230 days hospital stay and received 14 different lines (combination) of antibiotics.