Abstract:Mycotic pseudoaneurysm of aorta following cardiac surgery is rare but is highly fatal if it is unrecognized and untreated. Here, we report a case of a 45-year-old male patient who presented with rapidly progressive multiple pseudoaneurysms of the ascending aorta infected with multidrug resistant (MDR) Pseudomonas aeruginosa at 5 weeks after cardiac transplantation, on a background of prior bridging therapy with left ventricular assistant device (LVAD). The patient was successfully treated with the newer cephal… Show more
“…Furthermore, this review identified 30 publications reporting a total of 364 immunocompromised patients [ 22 , 26 , 27 , 30 , 34 , 37 – 39 , 41 , 43 , 48 , 49 , 51 , 53 , 59 – 61 , 63 , 68 , 73 , 79 , 83 – 86 , 90 , 91 , 96 – 98 ]. Immunocompromised patients include those with a history of organ transplant, disease suppressing immunity (e.g.…”
Section: Resultsmentioning
confidence: 99%
“…Furthermore, 15 single-patient case reports reported C/T durations exceeding the maximum label dose, with 12 reporting a duration of > 28 days, and three reporting a duration of > 42 days. All three that reported a duration of > 42 days administered 8-week courses of C/T [ 56 , 63 , 67 ]. Two patients received C/T for XDR P. aeruginosa osteomyelitis [ 56 , 67 ], and one received C/T for MDR P. aeruginosa mycotic pseudoaneurysm [ 63 ].…”
Background
Antibacterial-resistant gram-negative infections are a serious risk to global public health. Resistant Enterobacterales and Pseudomonas aeruginosa are highly prevalent, particularly in healthcare settings, and there are limited effective treatment options. Patients with infections caused by resistant pathogens have considerably worse outcomes, and incur significantly higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials. This review aimed to collate data on C/T use in clinical practice.
Methods
This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative infections up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.
Results
There were 83 studies comprising 3,701 patients were identified. The most common infections were respiratory infections (52.9% of reported infections), urinary tract infections (UTIs; 14.9%), and intra-abdominal infections (IAIs; 10.1%). Most patients included were seriously ill and had multiple comorbidities. The majority of patients had infections caused by P.aeruginosa (90.7%), of which 86.0% were antimicrobial-resistant. C/T was used as both a 1.5 g q8h and 3 g q8h dose, for a median duration of 7–56 days (varying between studies). Outcome rates were comparable between studies: clinical success rates ranged from 45.7 to 100.0%, with 27 studies (69%) reporting clinical success rates of > 70%; microbiological success rates ranged from 31 to 100%, with 14 studies (74%) reporting microbiological success rates of > 70%. Mortality rates ranged from 0 to 50%, with 31 studies (69%) reporting mortality rates of ≤ 20%. In comparative studies, C/T was as effective as aminoglycoside- or polymyxin-based regimens, and in some instances, significantly more effective.
Conclusions
The studies identified in this review demonstrate that C/T is effective in clinical practice, despite the diverse group of seriously ill patients, different levels of resistance of the pathogens treated, and varying dosing regimens used. Furthermore, comparative studies suggest that C/T offers a successful alternative to standard of care (SoC).
“…Furthermore, this review identified 30 publications reporting a total of 364 immunocompromised patients [ 22 , 26 , 27 , 30 , 34 , 37 – 39 , 41 , 43 , 48 , 49 , 51 , 53 , 59 – 61 , 63 , 68 , 73 , 79 , 83 – 86 , 90 , 91 , 96 – 98 ]. Immunocompromised patients include those with a history of organ transplant, disease suppressing immunity (e.g.…”
Section: Resultsmentioning
confidence: 99%
“…Furthermore, 15 single-patient case reports reported C/T durations exceeding the maximum label dose, with 12 reporting a duration of > 28 days, and three reporting a duration of > 42 days. All three that reported a duration of > 42 days administered 8-week courses of C/T [ 56 , 63 , 67 ]. Two patients received C/T for XDR P. aeruginosa osteomyelitis [ 56 , 67 ], and one received C/T for MDR P. aeruginosa mycotic pseudoaneurysm [ 63 ].…”
Background
Antibacterial-resistant gram-negative infections are a serious risk to global public health. Resistant Enterobacterales and Pseudomonas aeruginosa are highly prevalent, particularly in healthcare settings, and there are limited effective treatment options. Patients with infections caused by resistant pathogens have considerably worse outcomes, and incur significantly higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials. This review aimed to collate data on C/T use in clinical practice.
Methods
This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative infections up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.
Results
There were 83 studies comprising 3,701 patients were identified. The most common infections were respiratory infections (52.9% of reported infections), urinary tract infections (UTIs; 14.9%), and intra-abdominal infections (IAIs; 10.1%). Most patients included were seriously ill and had multiple comorbidities. The majority of patients had infections caused by P.aeruginosa (90.7%), of which 86.0% were antimicrobial-resistant. C/T was used as both a 1.5 g q8h and 3 g q8h dose, for a median duration of 7–56 days (varying between studies). Outcome rates were comparable between studies: clinical success rates ranged from 45.7 to 100.0%, with 27 studies (69%) reporting clinical success rates of > 70%; microbiological success rates ranged from 31 to 100%, with 14 studies (74%) reporting microbiological success rates of > 70%. Mortality rates ranged from 0 to 50%, with 31 studies (69%) reporting mortality rates of ≤ 20%. In comparative studies, C/T was as effective as aminoglycoside- or polymyxin-based regimens, and in some instances, significantly more effective.
Conclusions
The studies identified in this review demonstrate that C/T is effective in clinical practice, despite the diverse group of seriously ill patients, different levels of resistance of the pathogens treated, and varying dosing regimens used. Furthermore, comparative studies suggest that C/T offers a successful alternative to standard of care (SoC).
Background
Mycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient.
Case presentation
Our 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers.
Conclusions
Donor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.
“…In another recent study, C/T was successful in treating 15/21 patients with various MDR P. aeruginosa infections (71%), although it should be noted that resistance to C/T conferred by de novo mutations occurred in 14% of cases (3/21) [43]. Regarding case reports and small case series, they also mainly reported on the successful off-label use of C/T for treating infections due MDR P. aeruginosa (mostly pneumonia, bloodstream infections, osteomyelitis, and acute pulmonary exacerbation of cystic fibrosis) [54,[93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112]. More reports will come in the near future, that remain critical to enrich our knowledge about the effectiveness of C/T for all these indications.…”
Section: C/t In Mdr-p Aeruginosa In Many Countries Approximatelymentioning
Ceftolozane/tazobactam (C/T) is a new antibiotic resulting from the combination of a novel cephalosporin, structurally similar to ceftazidime, with tazobactam, a well-known beta-lactamase inhibitor. C/T remains active against extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multi-drug resistant (MDR) P. aeruginosa, and has been recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). A trial on hospital-acquired pneumonia is ongoing. Areas covered: The place in therapy of C/T is delineated by addressing the following main topics: (i) antimicrobial properties; (ii) pharmacological properties; (iii) results of clinical studies. Expert commentary: C/T is approved for cIAI and cUTI. However, the drug has a special value for clinicians in any kind of infectious localization for two main reasons. The first is that C/T is especially valuable in suspected or documented severe infections due to MDR P. aeruginosa, which is not a rare occurrence in many countries. The second is that C/T may provide an alternative to carbapenems for the treatment of infections caused by ESBL-producers, thus allowing a carbapenem-sparing strategy. Reporting of off-label use is mandatory to increase the body of evidence and the clinicians' confidence in using it for indications other than cIAI and cUTI.
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