The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that ...developed one episode or more of AB beyond the second month after transplantation were included in this open‐label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation 53 patients) or control group (no antimicrobial therapy 59 patients). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24‐mo follow‐up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug‐resistant bacteria, graft function and all‐cause mortality. There were no differences in the primary outcome in the intention‐to‐treat population (7.5% 4 of 53 in the treatment group vs. 8.4% 5 of 59 in the control group; odds ratio OR 0.88, 95% confidence interval CI 0.22–3.47) or the per‐protocol population (3.8% 1 of 26 in the treatment group vs. 8.0% 4 of 50 in the control group; OR 0.46, 95% CI 0.05–4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).
This randomized controlled trial shows no difference in the incidence of acute pyelonephritis between kidney transplant recipients who had all their episodes of asymptomatic bacteriuria treated and those who did not receive antimicrobial treatment for asymptomatic bacteriuria beyond the second month after transplantation. See the editorial from Blumberg on page 2779.
The epidemiology of respiratory viruses (RVs) in lung transplant recipients (LTRs) and the relationship of RVs to lung function, acute rejection (AR) and opportunistic infections in these patients ...are not well known. We performed a prospective cohort study (2009–2014) by collecting nasopharyngeal swabs (NPSs) from asymptomatic LTRs during seasonal changes and from LTRs with upper respiratory tract infectious disease (URTID), lower respiratory tract infectious disease (LRTID) and AR. NPSs were analyzed by multiplex polymerase chain reaction. Overall, 1094 NPSs were collected from 98 patients with a 23.6% positivity rate and mean follow‐up of 3.4 years (interquartile range 2.5–4.0 years). Approximately half of URTIDs (47 of 97, 48.5%) and tracheobronchitis cases (22 of 56, 39.3%) were caused by picornavirus, whereas pneumonia was caused mainly by paramyxovirus (four of nine, 44.4%) and influenza (two of nine, 22.2%). In LTRs with LRTID, lung function changed significantly at 1 mo (p = 0.03) and 3 mo (p = 0.04). In a nested case–control analysis, AR was associated with RVs (hazard ratio HR 6.54), Pseudomonas aeruginosa was associated with LRTID (HR 8.54), and cytomegalovirus (CMV) replication or disease was associated with URTID (HR 2.53) in the previous 3 mo. There was no association between RVs and Aspergillus spp. colonization or infection (HR 0.71). In conclusion, we documented a high incidence of RV infections in LTRs. LRTID produced significant lung function abnormalities. Associations were observed between AR and RVs, between P. aeruginosa colonization or infection and LRTID, and between CMV replication or disease and URTID.
A large prospective study of the epidemiology of respiratory viruses in lung transplant recipients using molecular assays demonstrates a very high incidence of respiratory viral infection and an association between respiratory virus infectious diseases, immediate allograft dysfunction, and the development of acute rejection and opportunistic infection.
Microbiological spectrum and outcome of infectious complications following small bowel transplantation (SBT) have not been thoroughly characterized. We performed a retrospective analysis of all ...patients undergoing SBT from 2004 to 2013 in Spain. Sixty‐nine patients underwent a total of 87 SBT procedures (65 pediatric, 22 adult). The median follow‐up was 867 days. Overall, 81 transplant patients (93.1%) developed 263 episodes of infection (incidence rate: 2.81 episodes per 1000 transplant‐days), with no significant differences between adult and pediatric populations. Most infections were bacterial (47.5%). Despite universal prophylaxis, 22 transplant patients (25.3%) developed cytomegalovirus disease, mainly in the form of enteritis. Specifically, 54 episodes of opportunistic infection (OI) occurred in 35 transplant patients. Infection was the major cause of mortality (17 of 24 deaths). Multivariate analysis identified retransplantation (hazard ratio HR: 2.21; 95% confidence interval CI: 1.02–4.80; p = 0.046) and posttransplant renal replacement therapy (RRT; HR: 4.19; 95% CI: 1.40–12.60; p = 0.011) as risk factors for OI. RRT was also a risk factor for invasive fungal disease (IFD; HR: 24.90; 95% CI: 5.35–115.91; p < 0.001). In conclusion, infection is the most frequent complication and the leading cause of death following SBT. Posttransplant RRT and retransplantation identify those recipients at high risk for developing OI and IFD.
Analysis of clinical and microbiological data of 87 small bowel transplant patients demonstrates that infection is a major complication after transplant, and retransplantation and the posttransplant requirement for renal replacement therapy are associated with a higher risk of developing opportunistic infections and invasive fungal disease.
We aimed to analyze the incidence, risk factors and impact of hypogammaglobulinemia (HGG) in 226 kidney transplant (KT) recipients in which serum immunoglobulin (Ig) levels were prospectively ...assessed at baseline, month 1 (T1), and month 6 (T6). The prevalence of IgG HGG increased from 6.6% (baseline) to 52.0% (T1) and subsequently decreased to 31.4% (T6) (p < 0.001). The presence of IgG HGG at baseline (odds ratio OR 26.9; p = 0.012) and a positive anti‐HCV status (OR 0.17; p = 0.023) emerged as risk factors for the occurrence of posttransplant IgG HGG. Patients with HGG of any class at T1 had higher incidences of overall (p = 0.018) and bacterial infection (p = 0.004), bacteremia (p = 0.054) and acute pyelonephritis (p = 0.003) in the intermediate period (months 1–6). Patients with HGG at T6 had higher incidences of overall (p = 0.004) and bacterial infection (p < 0.001) in the late period (>6 month). A complementary log–log model identified posttransplant HGG as an independent risk factor for overall (hazard ratio HR 2.03; p < 0.001) and bacterial infection (HR 2.68; p < 0.0001). Monitoring of humoral immunity identifies KT recipients at high risk of infection, offering the opportunity for preemptive immunoglobulin replacement therapy.
The authors analyze the incidence and clinical impact of hypogammaglobulinemia in kidney transplant recipients, and conclude that the systematic monitoring of humoral immunity identifies patients at high risk of posttransplant infection, offering the opportunity for preemptive immunoglobulin replacement therapy.
Antimicrobial stewardship programmes promote excellence in the use of antimicrobials by selecting the appropriate antimicrobial agent and the correct dose, route of administration and duration of ...treatment. However, there is limited experience with such programmes targeting antifungal treatments. We present the results of a non-compulsory programme for the control of antifungals. For 12 months, prescriptions of oral voriconazole or intravenous voriconazole, caspofungin and liposomal amphotericin B were reviewed, and non-compulsory recommendations were made. The incidence and outcome of fungal infections were examined. The results for the dispensed defined daily doses (DDDs) and expenditure on antifungals were compared with those for the previous 12 months. The number of antifungal treatments reviewed was 662. A recommendation to change treatment was made in 29% of the cases, including a change from intravenous to oral treatment (15%), cessation of antifungal treatment (8%), and a change to fluconazole (6%). The DDDs of intravenous voriconazole and caspofungin were reduced by 31.4% and 20.2%, respectively. The DDDs of oral voriconazole and dispensed vials of liposomal amphotericin B were increased by 8.2% and 13.9%, respectively. Expenditure on antifungals was reduced by US$370681.78 (11.8% reduction). The programme was not related to significant increases in the incidence of candidaemia, percentage of persistent/relapsing candidaemia cases, percentage of fluconazole-resistant Candida species, incidence of infections by filamentous fungi, or 12-month mortality in patients with filamentous fungal infections. In conclusion, a stewardship programme targeting antifungals achieved a reduction in antifungal expenditure without reducing the quality of care provided.
The risk factors for complications in patients with influenza A (H1N1)v virus infection have not been fully elucidated. We performed an observational analysis of a prospective cohort of hospitalized ...adults with confirmed pandemic influenza A (H1N1)v virus infection at 13 hospitals in Spain, between June 12 and November 10, 2009, to identify factors associated with severe disease. Severe disease was defined as the composite outcome of intensive‐care unit (ICU) admission or in‐hospital mortality. During the study period, 585 adult patients (median age 40 years) required hospitalization because of pandemic (H1N1) 2009. At least one comorbid condition was present in 318 (54.4%) patients. Pneumonia was diagnosed in 234 (43.2%) patients and bacterial co‐infection in 45 (7.6%). Severe disease occurred in 75 (12.8%) patients, of whom 71 required ICU admission and 13 (2.2%) died. Independent factors for severe disease were age <50 years (OR, 2.39; 95% CI, 1.05–5.47), chronic comorbid conditions (OR, 2.93; 95% CI, 1.41–6.09), morbid obesity (OR, 6.7; 95% CI, 2.25–20.19), concomitant and secondary bacterial co‐infection (OR, 2.78; 95% CI, 1.11–7) and early oseltamivir therapy (OR, 0.32; 95% CI 0.16–0.63). In conclusion, although adults hospitalized for pandemic (H1N1) 2009 suffer from significant morbidity, mortality is lower than that reported in the earliest studies. Younger age, chronic comorbid conditions, morbid obesity and bacterial co‐infection are independent risk factors for severe disease, whereas early oseltamivir therapy is a protective factor.
Background
Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT).
Methods
We compared species distribution and antimicrobial susceptibility patterns in 1052 isolates from ...urine cultures obtained in 2 different cohorts of kidney transplant recipients in a single center (Cohort A: 189 patients undergoing KT between January 2002 and December 2004 336 isolates; Cohort B: 115 patients undergoing KT between January 2011 and December 2013 716 isolates).
Results
Asymptomatic bacteriuria accounted for most of the isolates (86.9% in Cohort A and 92.3% in Cohort B). Klebsiella pneumoniae (9.5% vs. 15.6%), Pseudomonas aeruginosa (1.8% vs. 7.9%), and Enterobacter cloacae (0.6% vs. 3.1%) were significantly more common in Cohort B. The isolation of K. pneumoniae in Cohort B was associated with the occurrence of acute pyelonephritis (9.8% of all K. pneumoniae isolates vs. 2.8% of the remaining uropathogens; P = 0.001). Non‐susceptibility rates among Enterobacteriaceae in Cohort B were higher for every class of antibiotics (P ≤ 0.003) with the exception of fosfomycin. Compared to Cohort A, significant increases were seen in isolates from Cohort B for multidrug‐resistant (MDR) (43.9% vs. 67.8%, respectively; P = 0.001), extended‐spectrum beta‐lactamase (ESBL)‐producing (6.6% vs. 26.1%; P = 0.001), and carbapenemase‐producing Enterobacteriaceae strains (0.0% vs. 5.0%; P = 0.001). Such differences were mostly attributable to K. pneumoniae (as 54.5% and 13.4% of isolates in Cohort B were ESBL‐producing and carbapenemase‐producing, respectively). MDR isolates were responsible for 69.1% of episodes of symptomatic urinary tract infection in Cohort B.
Conclusion
The increase in resistance rates among Enterobacteriaceae uropathogens is significant and may have an effect on KT programs.
The usefulness of monitoring of complement levels in predicting the occurrence of infection in kidney transplant (KT) recipients remains largely unknown. We prospectively assessed serum complement ...levels (C3 and C4) at baseline and at months 1 and 6 in 270 patients undergoing KT. Adjusted hazard ratios (aHRs) for infection in each posttransplant period were estimated by Cox regression. The prevalence of C3 hypocomplementemia progressively decreased from 21.5% at baseline to 11.6% at month 6 (p = 0.017), whereas the prevalence of C4 hypocomplementemia rose from 3.7% at baseline to 9.2% at month 1 (p = 0.004). Patients with C3 hypocomplementemia at month 1 had higher incidences of overall (p = 0.002), bacterial (p = 0.004) and fungal infection (p = 0.019) in the intermediate period (months 1–6). On multivariate analysis C3 hypocomplementemia at month 1 emerged as a risk factor for overall (aHR 1.911; p = 0.009) and bacterial infection (aHR 2.130; p = 0.014) during the intermediate period, whereas C3 hypocomplementemia at month 6 predicted the occurrence of bacterial infection (aHR 3.347; p = 0.039) in the late period (>6 month). A simple monitoring strategy of serum C3 levels predicts the risk of posttransplant infectious complications in KT recipients.
In a broad cohort of kidney transplant recipients, the authors find that the presence of C3 hypocomplementemia at months 1 and 6 correlates with the subsequent occurrence of infectious complications, thus opening new opportunities in the design of simple, clinically applicable strategies of immune monitoring in these patients.
To evaluate the potential role of PCR-based assays in the over-diagnosis of Clostridium difficile infection (CDI) by using a validated diagnostic algorithm in daily clinical practice.
We performed a ...retrospective cohort study evaluating all C. difficile-positive stool samples identified at our institution during a 12-month period, to compare outcomes and recurrence rates between patients with a positive enzyme immunoassay (EIA) for both glutamate dehydrogenase (GDH) and toxin A/B (‘toxin-positive group’), with those with GDH-positive, toxin-negative samples in whom the diagnosis was made by a positive PCR-based assay (‘toxin–/PCR+ group’). Medical records were reviewed by two independent investigators blinded to the mode of diagnosis.
We analysed 231 first CDI episodes (106 (45.8 %) in the ‘toxin-positive group’ and 125 (54.1%) in the ‘toxin–/PCR+ group’). Both groups had similar baseline characteristics. Patients in the ‘toxin-positive group’ presented more frequently with a severe/severe complicated form than those in the ‘toxin–/PCR+ group’ (36 (33.9%) versus 24 (19.2%); p 0.011) and had more recurrences (27 (25.5%) versus 9 (7.2%); p 0.001). Diagnosis of CDI based on a GDH/toxin-positive EIA independently predicted severe/severe-complicated course (adjusted OR 2.11; 95% CI 1.06–4.22; p 0.033) and recurrence (adjusted OR 3.79; 95% CI 1.65–8.69; p 0.002). There were no differences in all-cause mortality (12.3% versus 12.0%; p 0.95) or CDI-attributable mortality (4.7% versus 4.8%; p 0.93).
Toxin-positive patients were more likely to have severe-complicated forms of CDI and recurrences. Nevertheless, CDI-related complications may still occasionally occur among toxin-negative patients diagnosed by PCR, which stresses the need for individualized clinical evaluation.
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the ...healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.
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