Pneumocystis jirovecii pneumonia in kidney transplantation

Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised renal transplant recipients. In recent years, PCP outbreaks in renal transplant centers have been reported in many countries. Person‐to‐person transmission between PCP patients and other recipients lacking prophylaxis is one of the possible sources of infection. To prevent infection, effective prophylaxis in susceptible patients is recommended. Trimethoprim‐sulfamethoxazole (TMP‐SMX) is the most effective drug for PCP prophylaxis, but its recommended duration of use after transplantation varies among the different guidelines. The European Renal Association recommends a prophylaxis period of 4 months after transplantation, the American Society of Transplantation (AST) 6–12 months, and the Kidney Disease Improving Global Outcomes guidelines 3–6 months. Lifelong prophylaxis with TMP‐SMX is not recommended in renal transplant recipients; however, in many cases, PCP has occurred after the recommended prophylaxis periods after transplantation. In this minireview, we discuss the risk factors including environmental‐nosocomial exposure; state‐of‐the‐art diagnosis, treatment, prophylaxis and isolation; and references to the AST 2009 guidelines with the aim of integrating our experience with PCP outbreaks into recent reports, and we discuss how renal transplant recipients can be protected from PCP.     

Late‐onset Pneumocystis jirovecii pneumonia in solid organ transplant recipients

Anti‐Pneumocystis prophylaxis is recommended for at least 6–12 months after solid organ transplantation, as most cases of Pneumocystis jirovecii pneumonia (PCP) occur during the first year post transplantation. Herein, we report 4 cases of late‐onset PCP (>1 year post transplant). PCP appeared in a range of 50–68 months post transplant. Two cases had history of humoral rejection episodes treated with rituximab, and the other 2 had low CD4+ T‐cell count (<200 cells/mm³) at the time of diagnosis. All 4 patients survived. In conclusion, although the number of cases is low, we must be aware of the possibility of late‐onset PCP in solid organ transplant patients. The role of previous use of rituximab or persistent CD4+ T‐cell lymphopenia should be addressed in future studies.     

Pneumocystis jirovecii pneumonia 13 years post renal transplant following a recurrent cytomegalovirus infection

Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) is a rare but serious infection that usually occurs within a year after solid organ transplantation. PCP may occur after 1 year post transplantation, but the rate is reported to be very low. Studies have shown an association between cytomegalovirus (CMV) infection in solid organ transplant patients and an increased risk of opportunistic infection. This increased risk is thought to be a result of the immunomodulatory effects of the CMV infection. We present a case of PCP infection occurring 13 years after a renal transplantation. This occurred following a recurrent CMV infection while the patient was on low‐dose immunosuppressants.     

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis

M.G.J. de Boer, F.P. Kroon, S. le Cessie, J.W. de Fijter, J.T. van Dissel. Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.
Transpl Infect Dis 2011: 13: 559–569. All rights reserved Abstract: Risk stratification‐based duration of trimethoprim‐sulfamethoxazole (TMP‐SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence‐based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time‐matched controls per case were enrolled. All patients were participants of the kidney transplantation program of the Leiden University Medical Center, a tertiary care hospital in the Netherlands. Potential risk factors were compared between groups by uni‐ and multivariate matched analyses. At transplantation, age >55 years (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3–5.9) and not receiving basiliximab induction therapy (adjusted OR 4.3, 95% CI 1.1–17.1) predicted development of PCP. In the final multivariate analysis, only cytomegalovirus infection (adjusted OR 3.0, 95% CI 1.2–7.9) and rejection treatment (adjusted OR 5.8, 95% CI 1.9–18) were found to be independently associated with PCP. Using the variables identified by the multivariate analyses, effects of different hypothetical chemoprophylaxis strategies were systematically evaluated. Exploring different scenarios showed that chemoprophylaxis in the first 6 months for all renal transplant patients – and during the first year posttransplantation for patients >55 years of age or those treated for rejection – would result in very low PCP incidence and optimal avoidance of TMP‐SMX toxicity. The results provide a rationale for further prospective study on targeted provision of chemoprophylaxis to prevent PCP in kidney transplant patients.     

No occurrence of Pneumocystis jiroveci (carinii) pneumonia in 120 adults undergoing myeloablative unrelated cord blood transplantation

Abstract: The incidence of pneumonia caused by Pneumocystis carinii (PCP) (organism now renamed Pneumocystis jiroveci) during the early period after cord blood transplantation (CBT) was studied in 120 adults. Initially 89 patients (74%) received oral administration of 2 single‐strength trimethoprim‐sulfamethoxazole (TMP‐SMZ) tablets twice daily from day ?21. In 45 of 89 patients (51%), TMP‐SMZ administration for a scheduled duration was completed. In the remaining 44 patients (49%), however, TMP‐SMZ administration was discontinued prior to day ?3 because of toxicity. Among these patients, 42 subsequently received aerosolized pentamidine (AP) on a median of day ?13 (range, ?20 to ?6). Thirty‐one patients (26%) received AP without TMP‐SMZ administration on a median of day ?14 (range, ?21 to ?9). None of the 120 patients were diagnosed with PCP within 100 days or 2 years after CBT; however, one patient who received AP before CBT but no prophylaxis after CBT developed cerebral toxoplasmosis on day +91. Pre‐transplant prophylaxis against PCP did not significantly affect transplantation‐related mortality or disease‐free survival at 2 years after CBT. The results suggest that PCP during the early period after CBT can be effectively prevented by any pre‐transplant prophylactic method.     

Minimal residual disease before and after transplantation for childhood acute lymphoblastic leukaemia: is there any room for intervention?

Eighty‐two children and adolescents who underwent allogeneic transplantation for acute lymphoblastic leukaemia in remission (period 2001–2011, median follow‐up 4·9 years) had been assessed for minimal residual disease (MRD) by real‐time quantitative polymerase chain reaction before and at 1, 3, 6, 9 and 12 months after transplantation. Five‐year event‐free survival (EFS) and cumulative incidence of relapse were 77·7% [standard error (SE) 5·7] and 11·4% (SE 4·4), respectively, for patients with pre‐transplant MRD <1 × 10^?4 (68%), versus 30·8% (SE 9·1; P < 0·001) and 61·5% (SE 9·5; P < 0·001), respectively, for those with MRD ≥1 × 10^?4 (32%). Pre‐transplant MRD ≥1 × 10^?4 was associated with a 9·2‐fold risk of relapse [95% confidence interval (CI) 3·54–23·88; P < 0·001] compared with patients with MRD <1 × 10^?4. Patients who received additional chemotherapy pre‐transplant to reduce MRD had a fivefold reduction of risk of failure (hazard ratio 0·19, CI 0·05–0·70, P = 0·01). Patients who experienced MRD positivity post‐transplant did not necessarily relapse (5‐year EFS 40·3%, SE 9·3), but had a 2·5‐fold risk of failure (CI 1·05–5·75; P = 0·04) if any MRD was detected in the first 100 d, which increased to 7·8‐fold (CI 2·2–27·78; P = 0·002) if detected after 6 months. Anticipated immunosuppression‐tapering according to MRD may have improved outcome, nevertheless all patients with post‐transplant MRD ≥1 × 10^?3 ultimately relapsed, regardless of immunosuppression discontinuation or donor‐lymphocyte‐infusion. In conclusion, MRD before transplantation had the strongest impact on relapse and MRD positivity after transplantation, mostly if detected early and at low levels, did not necessarily imply relapse. Additional intensified chemotherapy and modulation of immunosuppression may reduce relapse risk and improve ultimate outcome.     

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants

Abstract: Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1000 patient‐years (33 cases/6813 pt‐years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000‐pt year vs. heart 0.4% (3/686) or 1.4 per 1000‐pt year vs. liver 0.7% (3/439) or 2.1 per 1000‐pt year vs. renal 0.4% (3/733) or 1.2 per 1000‐pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.     

Absence of Pneumocystis jiroveci pneumonia in liver transplantation recipients receiving short‐term (3‐month) prophylaxis

Abstract: Pneumocystis jiroveci (formerly known as Pneumocystis carinii) is a fungal pathogen that causes pneumonia (PCP) in liver transplant recipients. Consequently, prophylaxis with trimethoprim–sulfamethoxazole (TMP/SMZ) is typically administered for at least 1 year at most liver transplant programs. At our center we have utilized a short‐term (3‐month) prophylactic regimen with TMP/SMZ for the past decade and report our experience and speculate on the potential widespread application of this approach. Methods. For patients transplanted at our center between January 1997 and January 2007, we recorded all documented PCP infections by review of our liver transplant database and hospital‐based electronic medical records system, both of which record all infections and culture results. Results. We recorded no cases of PCP in any of the liver transplant recipients at our center during the study period. Conclusions. We report the absence of PCP in a large cohort of liver transplant recipients receiving a short‐term (3‐month) prophylaxis with TMP/SMZ. These findings provide a rational basis to consider short‐term (3‐month) PCP prophylaxis or avoidance of prophylaxis altogether in selected low‐risk patients.     

Clofarabine-containing conditioning regimen for allo-SCT in AML/ALL patients: a survey from the Acute Leukemia Working Party of EBMT

Clofarabine (CLO), a second‐generation purine analogue, has demonstrated an efficient anti‐leukemia activity while showing a favorable toxicity profile. This retrospective multicenter report assessed the outcome of 90 patients who received a CLO‐containing conditioning regimen before allo‐SCT for AML (n = 69) or ALL (n = 21). Median age was 42 yr at transplant. The majority of cases (n = 66) presented with an active disease at transplant while 38 patients had received previous transplantation(s). A total of 88 and two patients received a reduced‐intensity conditioning or a myeloablative regimen, respectively. Engraftment was achieved in 97% of evaluable patients. With a median follow‐up of 14 months (range, 1–45), the 2‐year OS, LFS, relapse, and NRM rates were 28 ± 5%, 23 ± 5%, 41 ± 6%, and 35 ± 5%, respectively. When comparing AML and ALL patients, OS and LFS were significantly higher for AML (OS, 35 ± 6% vs. 0%, P < 0.0001); LFS: 30 ± 6% vs. 0%, P < 0.0001). In a Cox multivariate analysis, an AML diagnosis was the only factor associated with a better LFS ( HR = 0.37; 95%CI, 0.21–0.66; P = 0.001). We conclude that a CLO‐containing conditioning regimen prior to allo‐SCT might be an effective treatment. Prospective studies are needed to evaluate the potential role of CLO as part of conditioning regimens in acute leukemias.     

A case of Campylobacter jejuni bacteremia in a renal transplant patient

H. Aggarwal, L. Kushnir, D. Conti, M. Gallichio, E. Tobin. A case of Campylobacter jejuni bacteremia in a renal transplant patient
Transpl Infect Dis 2010: 12: 518–520. All rights reserved Abstract: Only 2 cases of Campylobacter bacteremia have been reported in renal transplant recipients, to our knowledge, with both resulting in significant morbidity and mortality. We present a case of a 56‐year‐old renal transplant recipient who presented with brief diarrheal illness followed by Campylobacter jejuni bacteremia. She remained asymptomatic for 5 days after initial presentation despite positive blood cultures. She was treated with levofloxacin for a total of 4 weeks and, fortunately, did not develop any complications. C. jejuni should be considered in the differential diagnosis as a potential cause of bacteremia in immunosuppressed renal transplant patients presenting with diarrheal illness.     

Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued?

Solid organ transplant recipients are at risk for Pneumocystis carinii pneumonia (PCP), but the risk of PCP beyond 1 year is poorly defined. We identified 25 cases of PCP in 1,299 patients undergoing solid organ transplantation between 1987 and 1996 at The Cleveland Clinic Foundation (4.8 cases per 1,000 person transplant-years [PTY]). Ten (36%) of 28 PCP cases (transplantation was performed before 1987 in three cases) occurred > or = 1 year after transplantation, and no patient developed PCP while receiving prophylaxis for PCP. The incidence of PCP during the first year following transplantation was eight times higher than that during subsequent years. The highest rate occurred among lung transplant recipients (22 cases per 1,000 PTY), for whom the incidence did not decline beyond the first year of transplantation. We conclude that the incidence of PCP is highest during the first year after transplantation and differs by type of solid organ transplant. Extending the duration of PCP prophylaxis beyond 1 year may be warranted for lung transplant recipients.     

Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in solid organ transplantation

Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae is spreading globally and represents a challenge in infection control and treatment. Solid organ transplant (SOT) recipients are especially at risk for infection by multidrug‐resistant bacteria, and little is known about infection with KPC‐producing organisms in this setting. The aim of this study was to describe the clinical and microbiologic aspects of KPC‐producing K. pneumoniae infections in SOT recipients. A KPC‐2‐producing K. pneumoniae outbreak was identified in a public teaching tertiary care hospital in São Paulo, Brazil, in June 2009. During the outbreak, cases of KPC‐2‐producing K. pneumoniae infection in SOT recipients occurred between July 2009 and February 2010; these cases were retrospectively reviewed. Overall, 12 episodes of infection with KPC‐producing K. pneumoniae occurred in 2 heart, 4 liver, and 6 kidney transplant recipients with incidence rates of 16.7%, 12.9%, and 26.3% in heart, liver, and kidney transplantation, respectively. Infection occurred at a median time of 20 days after transplantation. Primary infection sites were as follows: 4 urinary tract infections, 4 bloodstream infections, 2 pneumonias, and 2 surgical site infections. All patients except one had received antibiotics in the last 30 days, mostly piperacillin‐tazobactam or glycopeptides. All strains exhibited susceptibility to amikacin and gentamicin. Patients were treated with tigecycline plus polymyxin B (3 cases), polymyxin B plus carbapenem (3 cases), polymyxin B alone (3 cases), or tigecycline plus imipenem (1 case). In 2 cases, patients received only carbapenem, and death occurred before the final culture result. The overall 30‐day mortality rate was 42%. In this series of KPC‐producing K. pneumoniae infection in SOT recipients, the infection occurrence was high during an institutional outbreak and was potentially life threatening.     

Selective neutralization of the serpin protease nexin‐1 by a specific monoclonal antibody

Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC‐amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2‐year progression‐free survival rate (PFS) was 49% and 48% and 2‐year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2‐year PFS (59% vs. 23%, P = 0·006) but similar 2‐year OS as compared with SHL patients receiving R‐CHOP. SHL DLBCL patients treated with R‐CHOP, but not intensive induction, experienced significantly lower 2‐year PFS and OS (P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction.     

Hypercalcemia and pneumocystis Pneumonia after kidney transplantation: report of an exceptional case and literature review

C. Chatzikyrkou, C. Clajus, M. Haubitz, C. Hafer. Hypercalcemia and pneumocystis pneumonia after kidney transplantation: report of an exceptional case and literature review.
Transpl Infect Dis 2011: 13: 496–500. xx: 000–000. All rights reserved Abstract: Pneumocystis jirovecii remains an important pathogen in solid organ transplant recipients. Although the overall incidence may be decreasing, after the adoption of effective prophylactic measures, the risk has not been abolished, and pneumocystis pneumonia (PCP) can be observed even many years after successful transplantation. Hypercalcemia develops frequently after renal transplantation and is commonly associated with preexisting secondary hyperparathyroidism. But the pathogenesis of hypercalcemia occurring later in the course of transplantation may be different, and other disease states, such as malignancy and opportunistic infections, must be considered. Hypercalcemia in conjunction with PCP is being increasingly reported in renal transplant patients. In all the cases, respiratory symptoms were prominent, hypercalcemia was of mild‐to‐moderate severity, parathyroid hormone concentration was decreased, and 1,25(OH)₂D levels were extraordinarily or inappropriately high. We report the first case to our knowledge of severe hypercalcemia accompanying PCP, in a patient with previous total parathyroidectomy.     

Follow‐up of post‐transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react

Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days ?30, 30, 90 and 150 post‐transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre‐ or post‐transplant MRD status ≥10^?3. Only nine patients received DLI. Pre‐ and post‐transplant MRD status, and the duration of ciclosporin were independently associated with 5‐year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre‐transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post‐transplantation was a valuable prognostic tool to guide therapeutic intervention.     

Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case–control study

Objective. To analyze risk factors for Pneumocystis carinii pneumonia (PCP) in kidney transplant recipients. Study design. In a case–control study, 17 PCP cases diagnosed between July 1994 and July 2000 were matched with two controls each (previous and subsequent kidney transplant recipients who did not develop PCP during the same follow‐up period). Demographics, organ origin, human leukocyte antigen (HLA) mismatches, use of poly‐ or monoclonal anti‐CD3 antibodies (Po/MoAb) for induction or rejection treatment, rejection episodes, cumulative steroid dose for rejection treatment, immunosuppressive regimens, and other infections were analyzed. Results. No significant differences were seen in gender (male 10 vs. 15), mean age (39.7 vs. 35.4 years), organ origin (cadaver donor 13 vs. 19), HLA mismatches, or Po/MoAb use in induction treatment. Significant differences were observed in PCP cases for rejection history (P=0.02), and median and total number of rejection episodes (P=0.0018). The relative risks for PCP for 1, 2, and ≥3 rejection treatments vs. no such treatment were 1, 1.05, and 6.30, respectively (P=0.021). The relative risk for PCP for steroid‐resistant rejection was 4.34 (95% confidence interval [CI], 1.04–18.89) (P=0.019), and that for the use of Po/MoAb for rejection treatment was 7.23 (95% CI, 1.28–49.34) (P=0.006). The relative risk for PCP for 0, 1, and ≥2 previous or concomitant cytomegalovirus (CMV) infection vs. no such infections were 1.0, 2.32, and 13.0, respectively (P=0.012). The relative risks for PCP for tuberculosis (TB) was 18 (95% CI, 1.76–852.03), that for bacterial pneumonia was 14.22 (95% CI, 2.16–150.23), and that for hepatitis C virus infection was 5.25 (95% CI, 1.03–28.91). Immunosuppressive regimens with tacrolimus, mycophenolate mofetil (MMF), steroids (P=0.06), and MMF as a single variable (P=0.05) were more frequently used in cases. Primary trimethoprim‐sulfamethoxazole prophylaxis failure was observed in 12 patients in association with heavy immunosuppression and concomitant infections. Conclusions. The risk of PCP in kidney transplant recipients is related to the number and type of rejection treatments. It is also related to the occurrence of CMV infection, and to other immunomodulating infections such as TB and hepatitis C, and might also be increased with the use of newer and more potent immunosuppressive agents. Primary prophylaxis failure may occur in association with some of these risk factors.     

Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients

S. Gianella, L. Haeberli, B. Joos, B. Ledergerber, R.P.  Wüthrich, R. Weber, H. Kuster, P.M. Hauser, T. Fehr, N.J. Mueller. Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients.
Transpl Infect Dis 2010: 12: 1–10. All rights reserved
Abstract: Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised individuals. The epidemiology and pathogenesis of this infection are poorly understood, and the exact mode of transmission remains unclear. Recent studies reported clusters of PCP among immunocompromised patients, raising the suspicion of interhuman transmission. An unexpected increase of the incidence of PCP cases in our nephrology outpatient clinic prompted us to conduct a detailed analysis. Genotyping of 7 available specimens obtained from renal transplant recipients was performed using multi-locus DNA sequence typing (MLST). Fragments of 4 variable regions of the P. jirovecii genome (ITS1, 26S, mt26S, β-tubulin) were sequenced and compared with those of 4 independent control patients. MLST analysis revealed identical sequences of the 4 regions among all 7 renal allograft recipients with available samples, indicating an infection with the same P. jirovecii genotype. We observed that all but 1 of the 19 PCP-infected transplant recipients had at least 1 concomitant visit with another PCP-infected patient within a common waiting area. This study provides evidence that nosocomial transmission among immunocompromised patients may have occurred in our nephrology outpatient clinic. Our findings have epidemiological implications and suggest that prolonged chemoprophylaxis for PCP may be warranted in an era of more intense immunosuppression.     

Clinical impact of the use of 16S rRNA sequencing method for the identification of "difficult-to-identify" bacteria in immunocompromised hosts

Molecular method of 16S rRNA sequencing is reported to be helpful in the accurate identification of organisms with ambiguous phenotypic profiles. We analyzed the use of 16S rRNA sequencing method to identify clinically significant, “difficult‐to‐identify” bacteria recovered from clinical specimens, and evaluated its role in patient management and consequent clinical outcome. Among the 172 “difficult‐to‐identify” bacteria recovered over a 4‐year period, 140 were gram‐positive cocci or gram‐negative bacilli; identification by 16S rRNA did not play a role in the management of patients infected with these bacteria. From 32 patients, 33 “difficult‐to‐identify” gram‐positive bacilli were identified; the organisms were mycobacteria, Nocardia, Tsukamurella, Rhodococcus, and Gordonia. In 24 patients for whom clinical data were available, results from the 16S rRNA sequencing method led to treatment change in 14 immunocompromised patients (including 7 hematopoietic stem cell recipients and 1 liver transplant recipient). Therapy was modified in 9 patients, initiated in 3 patients, and discontinued in 2 patients. Most patients’ therapy was switched to oral antibiotics with discontinuation of intravascular catheters, facilitating early hospital discharge. All 14 patients were alive 30 days after infection onset. The present study demonstrates the clinical application of 16S rRNA sequencing method to identify “difficult‐to‐identify” mycobacteria and other gram‐positive bacilli in clinical specimens, particularly in immunocompromised hosts.