Pneumocystis Jirovecii Pneumonia Outbreaks Research Articles

Impact of Very Low-Dose Trimethoprim-Sulfamethoxazole on Serum Creatinine after Renal Transplantation: A Retrospective Study

BackgroundIt is well known that high-dose trimethoprim, through its effect of inhibiting creatinine secretion, increases serum creatinine levels without changes in real glomerular filtration rate. However, there has been no report regarding the effect of very low-dose trimethoprim on serum creatinine levels after renal transplantation. MethodsWe retrospectively investigated 76 renal transplantation recipient outpatients who completed their course of initial prophylaxis at our institution. Twelve patients who experienced events that might affect their serum creatinine levels were excluded. Fifty-one patients who required readministration of trimethoprim-sulfamethoxazole to prevent a possible outbreak of pneumocystis jirovecii pneumonia and 13 patients who did not receive readministration (control) were analyzed. Dosage was 80 mg/400 mg (per tablet), administered as 3 tablets per week for 30.6 ± 13.5 days. This study strictly complied with the Helsinki Congress and the Istanbul. Declaration regarding donor source. ResultsAll patients completed readministration without adverse events. Serum creatinine increased significantly in the readministration group (1.40 ± 0.64 mg/dL to 1.48 ± 0.70 mg/dL, P < .01) while not in the control group. The higher the initial serum creatinine level, the greater the increase of Δ serum creatinine (R = 0.59, P < .001). Sex, baseline urine protein level, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, donor type, and time after renal transplantation did not affect Δ serum creatinine. Serum creatinine returned to baseline levels after cessation. ConclusionsVery low-dose trimethoprim-sulfamethoxazole prophylaxis significantly raised serum creatinine reversibly by 6% after renal transplantation.

Outbreak-Causing Fungi: Pneumocystis jirovecii.

Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity in immunocompromised patients, with a higher mortality in non-HIV than in HIV patients. P. jirovecii is one of the rare transmissible pathogenic fungi and the only one that depends fully on the host to survive and proliferate. Transmissibility among humans is one of the main specificities of P. jirovecii. Hence, the description of multiple outbreaks raises questions regarding preventive care management of the disease, especially in the non-HIV population. Indeed, chemoprophylaxis is well codified in HIV patients but there is a trend for modifications of the recommendations in the non-HIV population. In this review, we aim to discuss the mode of transmission of P. jirovecii, identify published outbreaks of PCP and describe molecular tools available to study these outbreaks. Finally, we discuss public health and infection control implications of PCP outbreaks in hospital setting for in- and outpatients.

Hypercalcaemia preceding diagnosis of Pneumocystis jirovecii pneumonia in renal transplant recipients.

BackgroundThe overall incidence of Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients is 5–15%. A timely diagnosis of PJP is difficult and relies on imaging and detection of the organism.MethodsWe present a case series of four patients displaying hypercalcaemia with an eventual diagnosis of PJP and document the management of the outbreak with a multidisciplinary team approach. We discuss the underlying pathophysiology and previous reports of hypercalcaemia preceding a diagnosis of PJP. We also reviewed the evidence concerning PJP diagnosis and treatment.ResultsWithin our renal transplant cohort, four patients presented within 7 months with hypercalcaemia followed by an eventual diagnosis of PJP. We measured their corrected calcium, parathyroid hormone (PTH), 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 25-hydroxycholecalciferol [25(OH)D] levels at admission and following treatment of PJP. All four patients diagnosed with PJP were 4–20 years post-transplantation. Three of the four patients demonstrated PTH-independent hypercalcaemia (corrected calcium >3.0 mmol/L). The presence of high 1,25(OH)2D3 and low 25(OH)D levels suggest negation of the negative feedback mechanism possibly due to an extrarenal source; in this case, the alveolar macrophages. All four patients had resolution of their hypercalcaemia after treatment of PJP.ConclusionsGiven the outbreak of PJP in our renal transplant cohort, and based on previous experience from other units nationally, we implemented cohort-wide prophylaxis with trimethoprim–sulphamethoxazole for 12 months in consultation with our local infectious diseases unit. Within this period there have been no further local cases of PJP.

Outbreak of Pneumocystis jirovecii Infection Among Heart Transplant Recipients: Molecular Investigation and Management of an Interhuman Transmission.

An outbreak of Pneumocystis jirovecii pneumonia (PCP) occurred among heart transplant recipients (HTR) at the outpatient clinic of a university hospital, from March to September 2015. Clinical, therapeutic, biological, and molecular data were analyzed to determine its origin and control the outbreak. Clinical and biological data regarding all HTR followed in the outpatient clinic were collected. PCP diagnosis was based on microscopy and real-time polymerase chain reaction (PCR). Investigations were performed by building a transmission map, completed by genotyping Pneumocystis isolates and by a control of chemoprophylaxis observance. Asymptomatic exposed patients were screened for colonization using real-time PCR. Among 124 HTR, 7 PCP cases were confirmed. Screening identified 3 additional patients colonized by P. jirovecii. All patients were cured, and no further cases were identified after trimethoprim-sulfamethoxazole prophylaxis was introduced in the entire cohort. Genotyping demonstrated the same strain in all PCP cases and colonized patients. All cases were linked with possible transmission chains from 2 possible index patients. Interhuman transmission was significantly associated with more frequent visits in the outpatient clinic. Six cases were receiving atovaquone as a prophylaxis. The occurrence of PCP was significantly associated with atovaquone prophylaxis. This is the first outbreak with detailed molecular analysis in HTR so far. Genotyping and transmission chain confirmed interhuman transmission in all colonized/infected PCP cases. Outpatient clinic layout and high encounters probably caused this PCP cluster, which was controlled after systematic trimethoprim-sulfamethoxazole prophylaxis in exposed patients.

Lifelong Prophylaxis With Trimethoprim-Sulfamethoxazole for Prevention of Outbreak of Pneumocystis jirovecii Pneumonia in Kidney Transplant Recipients.

BackgroundOutbreaks of Pneumocystis jirovecii pneumonia (PCP) in kidney transplant recipients are frequently reported worldwide. However, the general guidelines propose only short-term prophylaxis with trimethoprim-sulfamethoxazole after kidney transplantation. We experienced 3 PCP outbreaks in the last 10 years despite providing the recommended prophylaxis. The purpose of this study was to find a prophylaxis regimen that could successfully prevent future PCP outbreaks in immunosuppressed kidney transplant recipients.MethodsOccurrence of PCP at our hospital since 2004 was reviewed. A total of 48 cases were diagnosed from July 2004 through December 2014. Genotypes of P. jirovecii were determined in these cases.ResultsThree PCP outbreaks by 3 different genotypes of P. jirovecii in each outbreak occurred with 2-year intervals in last 10 years. Molecular analysis showed that each intraoutbreak was caused by identical P. jirovecii, whereas interoutbreaks were caused by different genotypes. Although short-term prophylaxis was provided to all kidney recipients after each outbreak after identification of a single PCP case, additional outbreaks were not prevented because the universal prophylaxis had already been completed when new case of PCP emerged.ConclusionsThe contagious nature of P. jirovecii allows easy development of outbreaks of PCP in immunosuppressed kidney transplant recipients. Although the universal short-term prophylaxis is effective in controlling ongoing outbreak, lifelong prophylaxis of kidney transplant recipients should be considered to prevent new outbreaks.

(210) - First Outbreak of Pneumocystis jirovecii Pneumonia in Heart Transplantation Recipients

(210) - First Outbreak of Pneumocystis jirovecii Pneumonia in Heart Transplantation Recipients

Investigation of outbreaks of Pneumocystis jirovecii pneumonia in two Scottish renal units

Pneumocystis jirovecii is recognized as an opportunistic pathogen. In recent years, human-to-human transmission of P.jirovecii has been demonstrated. However, outbreaks of P.jirovecii infections are not well defined because the epidemiological setting that facilitates transmission is not fully understood. This article describes two outbreaks of P.jirovecii pneumonia (PCP) in renal transplant patients in the West of Scotland. In total, 25 patients in two geographically contiguous locations were affected. Allele B was identified as the dominant type, along with allele A3. It was not possible to determine the exact reason for clustering of cases, although the outpatient clinic setting featured in one of the outbreaks. The outbreaks ceased with the use of trimethoprim-sulphamethoxazole prophylaxis; the target populations that received prophylaxis were different in the two outbreaks. Infection control teams should be alert to the possibility of outbreaks of PCP.

Epidemiological Outbreaks of Pneumocystis jirovecii Pneumonia Are Not Limited to Kidney Transplant Recipients: Genotyping Confirms Common Source of Transmission in a Liver Transplantation Unit.

Over a 5-month period, four liver transplant patients at a single hospital were diagnosed with Pneumocystis jirovecii pneumonia (PCP). This unusually high incidence was investigated using molecular genotyping. Bronchoalveolar lavage fluids (BALF) obtained from the four liver recipients diagnosed with PCP were processed for multilocus sequence typing (MLST) at three loci (SOD, mt26s, and CYB). Twenty-four other BALF samples, which were positive for P. jirovecii and collected from 24 epidemiologically unrelated patients with clinical signs of PCP, were studied in parallel by use of the same method. Pneumocystis jirovecii isolates from the four liver recipients all had the same genotype, which was different from those of the isolates from all the epidemiologically unrelated individuals studied. These findings supported the hypothesis of a common source of contamination or even cross-transmission of a single P. jirovecii clone between the four liver recipients. Hospitalization mapping showed several possible encounters between these four patients, including outpatient consultations on one particular date when they all possibly met. This study demonstrates the value of molecular genotyping of P. jirovecii isolated from clinical samples for epidemiological investigation of PCP outbreaks. It is also the first description of a common source of exposure to a single P. jirovecii clone between liver transplant recipients and highlights the importance of prophylaxis in such a population.

Pneumocystis jirovecii Pneumonia Outbreaks in Renal Transplant Populations in Quebec, Canada: Clinical and Molecular Epidemiology

Pneumocystis jirovecii Pneumonia Outbreaks in Renal Transplant Populations in Quebec, Canada: Clinical and Molecular Epidemiology

Management of Pneumocystis jirovecii Pneumonia in Kidney Transplantation to Prevent Further Outbreak.

The outbreak of Pneumocystis jirovecii pneumonia (PJP) among kidney transplant recipients is emerging worldwide. It is important to control nosocomial PJP infection. A delay in diagnosis and treatment increases the number of reservoir patients and the number of cases of respiratory failure and death. Owing to the large number of kidney transplant recipients compared to other types of organ transplantation, there are greater opportunities for them to share the same time and space. Although the use of trimethoprim-sulfamethoxazole (TMP-SMX) as first choice in PJP prophylaxis is valuable for PJP that develops from infections by trophic forms, it cannot prevent or clear colonization, in which cysts are dominant. Colonization of P. jirovecii is cleared by macrophages. While recent immunosuppressive therapies have decreased the rate of rejection, over-suppressed macrophages caused by the higher levels of immunosuppression may decrease the eradication rate of colonization. Once a PJP cluster enters these populations, which are gathered in one place and uniformly undergoing immunosuppressive therapy for kidney transplantation, an outbreak can occur easily. Quick actions for PJP patients, other recipients, and medical staff of transplant centers are required. In future, lifelong prophylaxis may be required even in kidney transplant recipients.

Outbreak of Pneumocystis Pneumonia in Renal and Liver Transplant Patients Caused by Genotypically Distinct Strains of Pneumocystis jirovecii

An outbreak of 29 cases of Pneumocystis jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used. P. jirovecii isolates from 22 transplant cases, 2 colonized RTRs, and 19 Pneumocystis control samples were genotyped by restriction fragment length polymorphism and multilocus sequence typing analysis. Contact tracing was used to investigate transmission. Potential risk factors were compared between PCP cases and matched non-PCP transplant patients. Three unique Pneumocystis genotypes were shared among 19 of the RTRs, LTRs, and a colonized RTR in three distinct clusters, two of which overlapped temporally. In contrast, Pneumocystis control samples harbored a wide range of genotypes. Evidence of possible nosocomial transmission was observed. Among several potential risk factors, only cytomegalovirus viremia was consistently associated with PCP (P=0.03; P=0.009). Mycophenolate mofetil was associated with PCP risk only in the RTR population (P=0.04). We identified three large groups infected with unique strains of Pneumocystis and provide evidence of an outbreak profile and nosocomial transmission. LTRs may be infected in PCP outbreaks simultaneously with RTRs and by the same strains, most likely by interhuman transmission. Patients are at risk several years after transplantation, but the risk is highest during the first 6 months after transplantation. Because patients at risk cannot be identified clinically and outbreaks cannot be predicted, 6 months of PCP chemoprophylaxis should be considered for all RTRs and LTRs.

A Pneumocystis jirovecii pneumonia outbreak in a single kidney-transplant center: role of cytomegalovirus co-infection

Pneumocystis jirovecii pneumonia (PCP) and cytomegalovirus (CMV) infection represent possible complications of medical immunosuppression. Between 2005 and 2010, non-human immunodeficiency virus (HIV) PCP patients admitted to a nephrology unit were analyzed for outcome, CMV comorbidity, and patient-to-patient contacts prior to PCP. In contrast to 2002-2004 (no cases) and 2008-2010 (10 cases), a PCP outbreak of 29 kidney-transplant recipients and one patient with anti-glomerular basement membrane disease occurred between 2005 and 2007. None of the patients were on PCP chemoprophylaxis. In four PCP patients, the genotyping data of bronchoalveolar lavage specimen showed an identical Pneumocystis strain. PCP cases had a higher incidence of CMV infection (12 of 30 PCP patients) and CMV disease (four patients) when compared to matched PCP-free controls (p < 0.05). Cotrimoxazole and, if applicable, ganciclovir were started 2.0 ± 4.0days following admission, and immunosuppressive medication was reduced. In-hospital mortality was 10% and the three-year mortality was 20%. CMV co-infection did not affect mortality. CMV co-infection more frequently occurred during a cluster outbreak of non-HIV PCP in comparison to PCP-free controls. Here, CMV awareness and specific therapy of both CMV infection and PCP led to a comparatively favorable patient outcome. The role of patient isolation should be further investigated in incident non-HIV PCP.

Outbreak of Pneumocystis Jirovecii Pneumonia in a British Renal Transplant Centre: Evidence for human to human transmission, or an environmental source of infection: Category: Lesson in Microbiology & Infection Control

Apart from sporadic cases, a few outbreaks of Pneumocystis jirovecii pneumonia (PCP) have been reported in renal transplant patients (RTP). The mechanisms and modes of transmission in the outbreak setting are not yet established. The Royal Liverpool University Hospital (RLUH) provides ‘hub and spoke' follow-up of over 900 RTP. In the ten years, 1999-2008 only one case of PCP had been reported. We describe epidemiology, risk factors, genotyping and environmental sampling during one of the largest out-breaks in Europe amongst RTP.

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 4months after transplantation, the American Society of Transplantation (AST) 6-12months, and the Kidney Disease Improving Global Outcomes guidelines 3-6months. 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.

Molecular Evidence ofPneumocystisTransmission in Pediatric Transplant Unit

We describe an outbreak of Pneumocystis jirovecii pneumonia in a pediatric renal transplant unit, likely attributable to patient-to-patient transmission. Single-strand conformation polymorphism molecular typing showed that 3 affected patients had acquired the same 2 strains of Pneumocystis, which suggests interhuman infection. An infant with mitochondriopathy was the probable index patient.