1234. Can Susceptibility to One Carbapenem be Conferred to Another? Frequency of Discordance in Gram-negative Clinical Isolates

Abstract Background Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA) can exhibit resistance to one carbapenem while remaining susceptible to another. While case reports describing discrepant carbapenem susceptibilities are available, the authors are unaware of any literature reporting aggregate carbapenem susceptibility discrepancies at a hospital level. Methods Susceptibility data from April 1, 2017 - December 31, 2017 was extracted through an antibiogram report for a 706-bed hospital. Ertapenem, imipenem-cilastatin, and meropenem susceptibilities were captured and compared for common Enterobacterales and Pseudomonas aeruginosa. Organism identification was performed using Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) mass spectrometry. Antibiotic susceptibility testing was performed using BD PhoenixTM. Carbapenem susceptibilities were interpreted using the most updated Clinical and Laboratory Standards Institute (CLSI) breakpoints at the time of assessment (2021). Carbapenem discordance was defined as an organism being susceptible to one carbapenem and non- susceptible (intermediate or resistant) to another. Approval was obtained from the institution’s Institutional Review Board. Results Meropenem proved to be the most active antimicrobial for all organisms (Figure 1). Carbapenem susceptibility discordance ranged from 0%-23.8% (Table 1). There was a significant difference in the incidence of discordance between Enterobacterales and Pseudomonas aeruginosa isolates (2.6% vs. 6.1%, p < 0.001). Of the 20 Pseudomonas aeruginosa isolates with discordant carbapenem susceptibilities, 70% were meropenem susceptible/imipenem non-susceptible and 30% were imipenem susceptible/meropenem non-susceptible. The most common site for discordance was urine for both Enterobacterales and Pseudomonas aeruginosa. However, while there was a significant rate of discordance between sites for Pseudomonas isolates, this was not the case for Enterobacterales (Table 2). Figure 1: Carbapenem Susceptibility by Isolate Table 1: Frequency of Carbapenem Discordance Table 2: Frequency of Carbapenem Discordance by Site Conclusion Due to the wide range of susceptibility discordance, clinical implications can be drastic if an institution is relying on susceptibility of one carbapenem to confer susceptibility to another carbapenem. Disclosures All Authors: No reported disclosures


Session: P-72. Resistance Mechanisms
Background. Management of disseminated Nocardia (NC) infection in transplant recipients requires prolonged antimicrobial therapy. Treatment can be particularly challenging if NC is resistant to standard agents. Drug toxicities can further limit options. We present a series of transplant patients with multi-drug resistant, disseminated NC infection complicated by serious adverse reactions to sequential antimicrobials.
Methods. This is a prospective review monitoring response to treatment of disseminated NC as well as adverse events to therapies.
Results. The first case is a 66-year old heart transplant patient who presented with fever and cough. Investigations revealed N. otitidiscaviarum lung lesion and multiple brain abscesses. Trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid were started empirically. NC was fully susceptible to linezolid only, and intermediate to quinolones and tobramycin. Linezolid was switched to ciprofloxacin due to ongoing cytopenia, and dose of TMP-SMX was reduced due to renal insufficiency. Repeat brain MRI showed enlarging abscesses; regimen was changed to linezolid and moxifloxacin. Severe peripheral neuropathy led to linezolid discontinuation and initiation of high-dose doxycycline plus moxifloxacin. One year into therapy, he presented with a large aortic dissection. His long-term quinolone therapy was felt to be contributory. He underwent aortic stent placement and remains on doxycycline monotherapy. The second case is a 74-year old female renal transplant patient who presented with fevers. A perinephric abscess was found which grew N. farcinica resistant to floroquinolones and clarithromycin, and intermediate to doxycycline. Further imaging also revealed pulmonary and brain involvement. TMP-SMX was started but soon switched to linezolid due to acute kidney injury. One month later she presented with severe thrombocytopenia and subdural hematoma thought to be secondary to linezolid. She died despite surgery.
Conclusion. This series illustrates challenges encountered in the treatment of disseminated NC infection in transplant recipients. Multidrug resistant NC coupled with serious toxicities of therapies often severely limits treatment options. Counseling patients and closely monitoring for adverse events is essential.
Disclosures. Background. Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA) can exhibit resistance to one carbapenem while remaining susceptible to another. While case reports describing discrepant carbapenem susceptibilities are available, the authors are unaware of any literature reporting aggregate carbapenem susceptibility discrepancies at a hospital level.
Methods. Susceptibility data from April 1, 2017 -December 31, 2017 was extracted through an antibiogram report for a 706-bed hospital. Ertapenem, imipenem-cilastatin, and meropenem susceptibilities were captured and compared for common Enterobacterales and Pseudomonas aeruginosa. Organism identification was performed using Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) mass spectrometry. Antibiotic susceptibility testing was performed using BD Phoenix TM . Carbapenem susceptibilities were interpreted using the most updated Clinical and Laboratory Standards Institute (CLSI) breakpoints at the time of assessment (2021). Carbapenem discordance was defined as an organism being susceptible to one carbapenem and non-susceptible (intermediate or resistant) to another. Approval was obtained from the institution's Institutional Review Board.
Results. Meropenem proved to be the most active antimicrobial for all organisms ( Figure 1). Carbapenem susceptibility discordance ranged from 0%-23.8% (Table 1). There was a significant difference in the incidence of discordance between Enterobacterales and Pseudomonas aeruginosa isolates (2.6% vs. 6.1%, p < 0.001). Of the 20 Pseudomonas aeruginosa isolates with discordant carbapenem susceptibilities, 70% were meropenem susceptible/imipenem non-susceptible and 30% were imipenem susceptible/meropenem non-susceptible. The most common site for discordance was urine for both Enterobacterales and Pseudomonas aeruginosa. However, while there was a significant rate of discordance between sites for Pseudomonas isolates, this was not the case for Enterobacterales (Table 2).

Background. Stenotrophomonas maltophilia is a multidrug resistant organism with limited antibiotic treatment options. Sulfamethoxazole-trimethoprim (TMP-SMZ) is considered first line agent based on in vitro studies and clinical evidence.
Minocycline has been showed to be active on in vitro studies and also has been explored in small retrospective studies However, doxycycline in the same class has variable in susceptibility in in vitro studies and has not been evaluated for efficacy in treatment of S. maltophilia infections The purpose of this research is to compare minocycline and doxycycline to TMP-SMZ for treatment of S. maltophilia pneumonia.
Methods. This retrospective, multi-center study evaluated hospitalized patients treated for S. maltophilia pneumonia with minocycline, doxycycline, or TMP-SMZ for clinical success, microbiologic success, and recurrence or reinfection within 30 days that required treatment. The inclusion criteria were patients ≥18 years old with S. maltophilia confirmed on respiratory culture from January 2013 to November 2020. Patients were classified as treatment with tetracyclines (minocycline or doxycycline) or TMP-SMZ based on definitive agent used for ≥50% of the treatment course and a minimum of four days. Patients with S. maltophilia resistant or intermediate to definitive therapy, and patients with combination therapy for treatment for S. maltophilia pneumonia were excluded.
Results. A total of 21 patients were included in tetracyclines group and 59 patients included in TMP-SMZ group. There was no difference in clinical success (28.6% vs. 25.4%; P = 0.994) or microbiologic success (n=28, 55.6% vs. 66.4%; P= 0.677) between tetracyclines and TMP-SMZ, respectively. Recurrence or reinfection requiring treatment (n=24) was higher in the tetracyclines group but not statistically significant compared to TMP-SMZ (66.7% vs. 26.7%; P= 0.092). A subgroup analysis showed no difference between doxycycline, minocycline, and TMP-SMZ for these three aims.
Conclusion. Clinical and microbiologic success were similar in patients treated with tetracyclines compared to TMP-SMZ for S. maltophilia pneumonia. This data suggests minocycline and doxycycline may be an option to treat S. maltophilia pneumonia, but conclusive clinical data continues to be lacking.
Disclosures. Anthony Gentene, PharmD, advisory board with Theravance Biopharma and Mylan (Consultant) Background. Ceftaroline was initially approved by the US FDA in 2010 to treat skin and skin structure infection (SSSI) and community-acquired bacterial pneumonia (CABP). FDA approval was extended in 2015 to treat patients with SSSI and CABP who developed bacteremia. Moreover, ceftaroline has also been used off-label to treat other infection types. We evaluated the in vitro activity of ceftaroline against S. aureus isolated in US medical centers in 2018-2020.

Update on the In Vitro Activity of Ceftaroline against Staphylococcus aureus from United States (US) Medical Centers Stratified by Infection
Methods. A total of 9,268 S. aureus isolates were consecutively collected from 33 US medical centers in 2018-2020 and susceptibility tested by broth microdilution method against ceftaroline and comparators. Results were stratified by infection type and resistance profile.
Conclusion. Ceftaroline remained very active against contemporary (2018-2020) S. aureus from US medical centers, independent of infection type. Ceftaroline retained good activity against MRSA and isolates resistant to ERY, LEV, TET, and/or TMP-SMX.