Multidrug-resistant bacterial infections after liver transplantation: Prevalence, impact, and risk factors.

BACKGROUND & AIMS: Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT). METHODS: This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT. RESULTS: We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates. CONCLUSION: MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors. IMPACT AND IMPLICATIONS: Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation.

Tobramycin Systemic Absorption in Lung Transplant Recipients Treated With Inhaled Tobramycin: A Cohort Study.

Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.

Transplantation of organs from SARS-CoV-2-positive donors: Preliminary experience from Spain.

BACKGROUND: The utilization of non-lung organs from deceased donors with a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the time of donation can be lifesaving, although the safety of this policy must be assessed. METHODS: This is a nationwide, prospective study, reporting the experience on the utilization of non-lung organs from SARS-CoV-2-positive donors between December 15, 2020 and May 31, 2022 in Spain. RESULTS: A total of 69 patients received a solid organ transplant (41 kidney, 18 liver, 8 heart, and 2 combined liver-kidney) obtained from 32 donors with a positive SARS-CoV-2 PCR at the time of donation (four of them with a cycle threshold value <30). All recipients tested negative for SARS-CoV-2 and were free of coronavirus disease 2019 (COVID-19) symptoms prior to transplantation. Nasopharyngeal swab turned positive for SARS-CoV-2 PCR in 4 (5.8%) recipients at 3, 8, 11, and 20 days after transplantation, though evidence did not support a donor-derived COVID-19. Four kidney recipients lost their grafts and two patients died: one heart recipient due to cardiogenic shock and one combined liver-kidney recipient due to lung hypertension and right heart failure. Graft losses and patient deaths were deemed unrelated to the donor SARS-CoV-2 status by the treating teams. No other adverse reactions were reported. CONCLUSIONS: This preliminary experience supports the safety of the use of organs other than lungs from SARS-CoV-2 PCR-positive donors, in alignment with previous series. However, the impact of SARS-CoV-2 infection upon organ quality should be established in future research.

Genotypic and Phenotypic Study of Antiviral Resistance Mutations in Refractory Cytomegalovirus Infection.

BACKGROUND: This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients. METHODS AND RESULTS: Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients. The genotype-phenotype correlation study resolved the status of 5 uncharacterized UL54 deoxyribonucleic acid polymerase (G441S, A543V, F460S, R512C, A928T) and 2 UL56 terminase (F345L, P800L) mutations found in clinical isolates. A928T conferred high, triple resistance to ganciclovir, foscarnet, and cidofovir, and A543V had 10-fold reduced susceptibility to cidofovir. Viral growth assays showed G441S, A543V, F345L, and P800L impaired viral growth capacities compared with wild-type AD169 HCMV. Three-dimensional modeling predicted A543V and A928T phenotypes but not R512C, reinforcing the need for individual characterization of mutations by recombinant phenotyping. CONCLUSIONS: Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.

Incidence and risk factors for early readmission after hospitalization for SARS-CoV-2 infection: results from a retrospective cohort study.

PURPOSE: We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19. METHODS: We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d'Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission RESULTS: A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7-33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35-12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21-6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01-5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89-46.48; p = 0.001) were the risk factors statistically associated with early readmission. CONCLUSION: Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.

Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation.

BACKGROUND: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. METHODS: CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-γ [IFN-γ] ≥ 0.2 IU/mL) indicated a positive CMV-CMI. RESULTS: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-γ level (>12 IU/mL vs ≤12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-γ level ≤12 IU/mL. CONCLUSIONS: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-γ level, but not the ATG dose, shows a strong association with the kinetics of this recovery.

Nebulized Micafungin Treatment for Scopulariopsis/Microascus Tracheobronchitis in Lung Transplant Recipients.

Scopulariopsis/Microascus isolates cause infections with high mortality in lung transplant recipients. Treatment is challenging due to antimicrobial resistance. We describe two cases of Scopulariopsis/Microascus tracheobronchitis in lung transplant recipients successfully treated with nebulized micafungin. This antifungal was well tolerated and achieved high concentrations in epithelial lining fluid up to 14 h after nebulization without significant plasma concentrations. Nebulized micafungin may be a safe and effective option for the treatment of fungal tracheobronchitis.

Low seroprevalence of SARS-CoV-2 antibodies in a liver transplant cohort.

Solid organ transplant recipients might be at greater risk for acquisition and mortality because of SARS-CoV-2. There are no data regarding SARS-CoV-2 seroprevalence among liver transplant (LT) recipients, and whether it is different from that of the general population or other immunosuppressed groups. We evaluated the prevalence of IgG SARS-CoV-2 antibodies among LT recipients to estimate the frequency of asymptomatic SARS-CoV-2 infection using serological assays in our outpatient clinic. We conducted a cross-sectional analysis from 10 May to 26 October 2020 of all adult (>18 years) LT recipients that underwent a routine laboratory test for the outpatient clinic follow-up at the Hospital Universitari Vall d'Hebron (Barcelona) in which we included serological testing for SARS-CoV-2. Nine out of 294 LT recipients (3.1%) tested positive for anti-SARS-CoV-2 IgG antibodies. Five of them (55.5%) had suffered clinically symptomatic SARS-CoV-2 infection confirmed by RT-PCR, four (44.4%) had presented compatible symptoms but without microbiological confirmation and only one patient (1/9, 11.1%) tested positive without any previous symptom. SARS-CoV-2 seroprevalence among LT recipients in an area highly affected by the pandemic is lower than in the general population in the same area. These results render the possibility of asymptomatic infection in LT recipients very unlikely.

Secondary syphilis with liver involvement in a liver transplant recipient.

Syphilis is capable of compromising almost any organ; however, syphilitic hepatitis is a rare manifestation that has been described most often in HIV-infected patients. Herein, we present a 33-year-old male liver transplant recipient who presented with progressive liver dysfunction characterized by mild ALT elevation and rising cholestasis, malaise, skin rash, and alopecia. Skin biopsy was characteristic of secondary syphilis, confirmed by both skin and liver biopsy-positive immunohistochemical staining for Treponema pallidum. The patient was treated with benzathine penicillin G 2.4 million units IM q week × 3 weeks. Three months later, the patient was asymptomatic and recovered from his general malaise. He showed no skin lesions and demonstrated complete regrowth of the hair on his scalp, beard, and eyebrows. The presence of liver dysfunction with cholestasis in a transplant recipient should alert transplant providers to the possibility of syphilitic hepatitis, particularly in men who have sex with men. Though not an early manifestation, cutaneous signs of secondary syphilis may be a helpful diagnostic indicator in most cases.

A New Clinical and Immunovirological Score for Predicting the Risk of Late Severe Infection in Solid Organ Transplant Recipients: The CLIV Score.

BACKGROUND: We aimed at constructing a composite score based on Epstein-Barr virus DNAemia (EBVd) and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in solid organ transplantation (SOT) recipients. METHODS: Kidney and liver transplant recipients between May 2014 and August 2016 at 4 participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole blood EBVd were determined at months 1, 3, and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI. RESULTS: Overall, 309 SOT recipients were followed-up for a median of 1000 days from transplant (interquartile range, 822-1124). Late severe infection occurred in 104 patients (33.6%). The CLIV Score consisted of the following variables at month 6: high-level EBVd (>1500 IU/mL) and recurrent infection during the previous months (6 points); recipient age ≥70 years and chronic graft dysfunction (5 points); cytomegalovirus mismatch (4 points); and CD8+ T-cell count <400 cells/µL (2 points). The area under receiver operating characteristics curve was 0.77 (95% confidence interval, 0.71-0.84). The risk of LI at day 1000 was as follows: score 0, 12.6%; score 2-5, 25.5%; score 6-9, 52.7%; score ≥10, 73.5%. CONCLUSIONS: While waiting for further external validation, the CLIV Score based on clinical and immune-virological parameters is potentially useful to stratify the risk of LI after SOT.

Routine Bile Culture From Liver Donors as Screening of Donor-Transmitted Infections in Liver Transplantation.

Bacterial infections are an important threat in the early post-liver transplantation period. Donor-transmitted infections, although rare, can have high mortality. The utility of routine culture from the donor bile duct as screening of donor-transmitted infection has not been evaluated. We performed a retrospective study of 200 consecutive liver transplants between 2010 and 2015. Demographic, clinical, and microbiological data were collected from the recipients' medical records. Clinical data included pretransplantation, perioperative, and posttransplantation information (until 30 days after the procedure). The 3-month patient survival and/or retransplantation were recorded. A total of 157 samples from the donor bile duct were collected and cultured. Only 8 were positive. The microorganisms isolated were as follows: Klebsiella pneumoniae, n = 2; Escherichia coli, n = 1; Enterobacter cloacae, n = 1; Streptococcus anginosus, n = 1; Streptococcus sp., n = 1; multiple gram-negative bacilli, n = 1; and polymicrobial, n = 1. All of the microorganisms were susceptible to the antibiotic prophylaxis administered. During the first month after transplantation, 81 recipients developed 131 infections. Only 1 of these recipients had a donor with a positive bile culture, and none of the infections were due to the microorganism isolated in the donor's bile. The 3-month overall survival was 89.5%, and there were no differences between recipients with positive donor bile cultures and those with negative donor bile cultures (87.5% versus 89.26%; P > 0.99). Routine testing of donor bile cultures does not predict recipients' infection or survival after liver transplantation and should not be recommended.

Community-acquired Respiratory Viruses Are a Risk Factor for Chronic Lung Allograft Dysfunction.

BACKGROUND: The relationship between community-acquired respiratory viruses (CARVs) and chronic lung allograft dysfunction (CLAD) in lung transplant recipients is still controversial. METHODS: We performed a prospective cohort study (2009-2014) in all consecutive adult patients (≥18 years) undergoing lung transplantation in the Hospital Universitari Vall d'Hebron (Barcelona, Spain). We systematically collected nasopharyngeal swabs from asymptomatic patients during seasonal changes, from patients with upper respiratory tract infectious disease, lower respiratory tract infectious disease (LRTID), or acute rejection. Nasopharyngeal swabs were analyzed by multiplex polymerase chain reaction. Primary outcome was to evaluate the potential association of CARVs and development of CLAD. Time-dependent Cox regression models were performed to identify the independent risk factors for CLAD. RESULTS: Overall, 98 patients (67 bilateral lung transplant recipients; 63.3% male; mean age, 49.9 years) were included. Mean postoperative follow-up was 3.4 years (interquartile range [IQR], 2.5-4.0 years). Thirty-eight lung transplant recipients (38.8%) developed CLAD, in a median time of 20.4 months (IQR, 12-30.4 months). In time-controlled multivariate analysis, CARV-LRTID (hazard ratio [HR], 3.00 [95% confidence interval {CI}, 1.52-5.91]; P = .002), acute rejection (HR, 2.97 [95% CI, 1.51-5.83]; P = .002), and cytomegalovirus pneumonitis (HR, 3.76 [95% CI, 1.23-11.49]; P = .02) were independent risk factors associated with developing CLAD. CONCLUSIONS: Lung transplant recipients with CARVs in the lower respiratory tract are at increased risk to develop CLAD.

Invasive mould infections in solid organ transplant patients: modifiers and indicators of disease and treatment response.

PURPOSE: Invasive mould infections, in particular invasive aspergillosis (IA), are comparatively frequent complications of immunosuppression in patients undergoing solid organ transplantation (SOT). Guidelines provide recommendations as to the procedures to be carried out to diagnose and treat IA, but only limited advice for SOT recipients. METHODS: Literature review and expert consensus summarising the existing evidence related to prophylaxis, diagnosis, treatment and assessment of response to IA and infections by Mucorales in SOT patients RESULTS: Response to therapy should be assessed early and at regular intervals. No indications of improvement should lead to a prompt change of the antifungal treatment, to account for possible infections by Mucorales or other moulds such as Scedosporium. Imaging techniques, especially CT scan and possibly angiography carried out at regular intervals during early and long-term follow-up and coupled with a careful clinical diagnostic workout, should be evaluated as diagnostic tools and outcome predictors, and standardised to improve therapy monitoring. The role of biomarkers such as the galactomannan test and PCR, as well as selected inflammation parameters, has not yet been definitively assessed in the SOT population and needs to be studied further. The therapeutic workup should consider a reduction of immunosuppressive therapy. CONCLUSIONS: The role of immunosuppression and immune tolerance mechanisms in the response to invasive fungal infection treatment is an important factor in the SOT population and should not be underestimated. The choice of the antifungal should consider not only their toxicity but also their effects on the immune system, two features that are intertwined.

Lung transplantation in two cystic fibrosis patients infected with previously pandrug-resistant Burkholderia cepacia complex treated with ceftazidime-avibactam.

We describe two cystic fibrosis patients infected with pandrug-resistant Burkholderia cepacia complex, with the exception of ceftazidime-avibactam, who received prophylaxis with this antibiotic during lung transplantation. Although both patients had a post-operative relapse of respiratory infection, one with positive blood cultures, ceftazidime-avibactam treatment yielded a favourable outcome. 12 months after transplantation, one patient presented an excellent clinical outcome. However, the other patient died 10 months later due to severe B. cepacia sinusitis with intracranial invasion.

Endotipsitis as an indication for pediatric liver transplantation.

Endotipsitis is a rare but severe complication of transjugular intrahepatic portosystemic shunt (TIPS), a device widely used to treat portal hypertension in adults, but sparsely used in children. We report a case of endotipsitis in a 3-year-old child affected of biliary atresia. She underwent a Kasai procedure at 3 months of age but, although the bile flow was restored, she presented upper gastrointestinal bleeding due to portal hypertension 1.5 years later. A TIPS was placed in order to control the hemorrhage. A year after TIPS placement, she started presenting repeated episodes of cholangitis. Blood cultures were positive to Enterobacter cloacae. Even with long antibiotic courses, adjusted to blood cultures, infectious signs were observed after antibiotic withdrawal. Device infection was demonstrated through Positron emission tomography-Computed tomography scan. The patient was listed for liver transplantation, and intravenous antibiotic treatment was maintained until stent removal during the liver transplant 8 months later. No infectious complications were demonstrated after the surgery. To the best of our knowledge, this is the first case report of endotipsitis described in a pediatric patient.

Phaeohyphomycosis caused by Medicopsis romeroi in solid organ transplant recipients: Report of two cases and comprehensive review of the literature.

Medicopsis romeroi is a melanized coelomycetous fungus, mainly found in tropical and subtropical regions and an uncommon cause of infection in solid organ transplant (SOT) recipients. We describe two cases of SOT recipients diagnosed with phaeohyphomycosis due to M romeroi and provide a comprehensive literature review. These infections should be considered in patients native to tropical countries with a localized skin and soft tissue infection. Sequencing is needed for accurate identification of uncommon melanized fungi. Surgical treatment is recommended to cure the infection and co-adjunctive oral antifungals should be considered.

Toxoplasmosis in Transplant Recipients, Europe, 2010-2014.

Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010-2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management.

Clinical Characteristics and Outcome of Lung Transplant Recipients with Respiratory Isolation of Corynebacterium spp.

Although chronic respiratory disease and immunosuppression are risk factors for Corynebacterium species respiratory infection, data are scarce regarding this disease in lung transplantation. Our aim was to describe the clinical characteristics and outcomes of lung transplant recipients (LTR) with respiratory isolation of Corynebacterium spp. This was a retrospective observational study performed at a referral center in Barcelona, Spain (2014 to 2016). We included all LTR in whom Corynebacterium spp. were isolated in at least one good-quality lower respiratory tract specimen. Overall, 24 of 527 (4.6%) LTR at risk during the study period were included. The main epidemiological, clinical, and microbiological data were analyzed. The most frequently isolated species were C. striatum (11/24), C. pseudodiphtheriticum (3/24), and C. amycolatum (3/24). All 19 (76%) patients who underwent bronchoscopy showed abnormalities, mainly mucosal plaques at the bronchial suture and purulent secretions. Clinical cure was achieved in 8/12 (67%) patients who fulfilled the CDC definition of lower respiratory tract infection (LRTI). To assess the clinical relevance of Corynebacterium spp., only patients with monomicrobial isolation (n = 18) were evaluated. LRTI was diagnosed in 9, and a nonsignificant association was found with a significant number of Corynebacterium sp. CFU/ml (7/9 LRTI versus 2/9 non-LRTI, P = 0.057). Persistent infection was associated with metallic bronchial stent implantation (4/4 versus 2/14, P = 0.005). The isolation of Corynebacterium spp. in respiratory specimens of lung transplant recipients may herald a respiratory tract infection or bronchial suture damage. Bronchial stent implantation is a risk factor for the persistence of Corynebacterium species infection.

Ceftolozane/tazobactam for the treatment of XDR Pseudomonas aeruginosa infections.

PURPOSE: The aim of this study was to evaluate the effectiveness of ceftolozane/tazobactam (C/T) for treating extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) infections, and to analyze whether high C/T dosing (2 g ceftolozane and 1 g tazobactam every 8 h) and infection source control have an impact on outcome. METHODS: Retrospective study of all consecutive patients treated with C/T for XDR-PA infection at a tertiary referral hospital (November 2015-July 2017). Main clinical and microbiological variables were analyzed. RESULTS: Thirty-eight patients were included. Median age was 59.5 years and Charlson Comorbidity Index was 3.5. Fourteen (36.8%) patients had respiratory tract infection, six (15.8%) soft tissue, and six (15.8%) urinary tract infection. Twenty-three (60.5%) received high-dose C/T and in 24 (63.2%) C/T was combined with other antibiotics. At completion of treatment, 33 (86.8%) patients showed clinical response. At 90 days of follow-up, 26 (68.4%) achieved clinical cure, and 12 (31.6%) had clinical failure because of persistent infection in one patient, death attributable to the XDR-PA infection in four, and clinical recurrence in seven. All-cause mortality was 5 (13.2%). Lower C/T MIC and adequate infection source control were the only variables significantly associated with clinical cure. CONCLUSIONS: C/T should be considered for treating XDR-PA infections, with infection source control being an important factor to avoid failure and resistance.