Ventilator-associated pneumonia is a severe complication among patients undergoing cardiac

surgery. Although hospital-acquired bacterial pathogens, often multidrug resistant, are the most

frequent cause, non-bacterial atypical and opportunistic agents traditionally associated with

immunocompromise are increasingly recognized. We describe ventilator-associated pneumonia

due to Pneumocystis jirovecii in the absence of traditional risk factors for Pneumocystis

pneumonia in a patient after cardiac surgery

Cifuentes, M

Miller, RF

Silva, F

Tobar, E

Vargas, SL

Zamorano, A

UCL Discovery

Grand Rounds Vol 14 pages 24–28Specialities: Infection and ImmunityArticle Type: Case ReportDOI: 10.1102/1470-5206.2014.0004 2014 e-MED LtdVentilator-associated pneumonia afterelective cardiac surgery caused byPneumocystis jiroveciiEduardo Tobara,b, Francisco Silvab, Anibal Zamoranoc, Marcela Cifuentesb,Robert F. Millerd,e and Sergio L VargasfaUnidad de Pacientes Crı´ticos, Departamento de Medicina, Hospital Clı´nico Universidad de Chile,Avenida Santos Dumont 999, Independencia 8380456, Santiago, Chile; bUnidad de Prevencio´n yControl de Infecciones Asociadas a la Atencio´n en Salud (UPC-IAAS), Hospital Clı´nico Universidadde Chile, Avenida Santos Dumont 999, Independencia 8380456, Santiago, Chile; cCentroCardiovascular, Hospital Clı´nico Universidad de Chile, Avenida Santos Dumont 999, Independencia8380456, Santiago, Chile; dResearch Department of Infection and Population Health, Institute ofEpidemiology and Healthcare, University College London, Mortimer Market, London, WC1E 6JB, UK;eClinical Research Department, London School of Hygiene and Tropical Medicine, Kepple Street,London, WC1E 7HT, UK; fPrograma de Microbiologı´a y Micologı´a, Instituto de Ciencias Biome´dicas,Facultad de Medicina, Universidad de Chile, Independencia 1027, Independencia 8380453,Santiago, ChileCorresponding address: Professor Robert Miller, Research Department of Infection and PopulationHealth, Institute of Epidemiology and Healthcare, University College London, Mortimer MarketCentre, off Capper Street, London, WC1E 6JB, UK.Email: robert.miller@ucl.ac.ukDate accepted for publication 16 June 2014AbstractVentilator-associated pneumonia is a severe complication among patients undergoing cardiacsurgery. Although hospital-acquired bacterial pathogens, often multidrug resistant, are the mostfrequent cause, non-bacterial atypical and opportunistic agents traditionally associated withimmunocompromise are increasingly recognized. We describe ventilator-associated pneumoniadue to Pneumocystis jirovecii in the absence of traditional risk factors for Pneumocystispneumonia in a patient after cardiac surgery.KeywordsVentilator-associated pneumonia; Pneumocystis jirovecii; cardiac surgery; intensive care.IntroductionVentilator-associated pneumonia (VAP) is an important condition, given its morbidity, mortalityand associated health care costs[1]. Common causes of VAP include multidrug-resistant bacteriasuch as Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia andmethicillin-resistant Staphylococcus aureus[2], however atypical and opportunistic pathogens,This paper is available online at http://www.grandrounds-e-med.com. In the event of a change in the URLaddress, please use the DOI provided to locate the paper.including Chlamydia pneumoniae and Mycoplasma pneumoniae, Candida albicans and otherfungi, are increasingly recognized in patients who have undergone cardiothoracic surgery[3,4]. Wedescribe a patient with VAP caused by another opportunistic organism, Pneumocystis jirovecii, inthe absence of traditional risk factors for Pneumocystis pneumonia (PCP).Case reportA 64-year-old woman with rheumatic mitral valve disease presented with progressive impairmentof functional capacity resulting in heart failure (New York Heart Association Functional Class III).Her past medical history was unremarkable and the patient was not taking corticosteroids orother immunosuppressive therapy. On examination, the patient had a normal nutritional status(body mass index¼19.5kg/m2), there was no lymphadenopathy or organomegaly, and nostigmata of Cushing syndrome were evident. Echocardiography showed moderate to severemitral regurgitation, mild mitral stenosis, a left ventricular ejection fraction of 40%, and severetricuspid regurgitation. Coronary angiography and a high-resolution chest computed tomography(CT) scan were normal. A human immunodeficiency virus (HIV) test (ELISA combined HIV-1 andHIV-2 antibody plus HIV-1 p24 antigen) was negative, and blood glucose and serum albuminlevels, neutrophil and total lymphocyte counts, and biochemical tests of renal, liver, and bonefunction were normal.The patient underwent mitral valve replacement (Carpentier Edwards PERIMOUNT; EdwardsLifesciences, Irvine, CA) and tricuspid valve repair surgery. During the immediate (2–8h)postoperative period she developed cardiovascular instability requiring vasopressor supportand mechanical ventilation. Echocardiography revealed moderate biventricular systolic dysfunc-tion without an abnormal mitral gradient. Vasopressor drugs were withdrawn, loop diuretics werestarted, and weaning from mechanical ventilation was achieved by 24h postoperatively.Despite a negative fluid balance and intermittent non-invasive ventilatory bilevel positive airwaypressure, the patient deteriorated, with increased work of breathing, hypoxemia (Pao2:Fio2 ratio5150), and radiographic evidence of new infiltrates, and was re-intubated on the fifthpostoperative day. The acute lung injury was ascribed to VAP; inflammatory markers showedwhite blood cells (WBC)¼18,200 cells/ml, C-reactive protein¼300mg/l (normal 55mg/l) andprocalcitonin¼5.9ng/ml (normal50.15ng/ml). After collecting urine, peripheral and central lineblood samples for culture, and an endotracheal aspirate for quantitative cultures, empiricantibiotic therapy was initiated with piperacillin/tazobactam with vancomycin.A CT scan of the chest, done 6h before re-intubation showed diffuse bilateral alveolarinfiltrates and ground-glass opacities with sparing of the basal segments of the lower left lobe.The patient deteriorated, developing cardiovascular failure requiring vasopressor and inotropicsupport. Microbiological studies were negative, and so vancomycin was stopped and piperacillin/tazobactam was continued. The patient stabilized hemodynamically, and inflammatory markersimproved (WBC¼13,400 cells/ml, C-reactive protein¼74mg/l, and procalcitonin¼0.88ng/ml);serum amylase and bilirubin levels were normal.By the eighth day of mechanical ventilation, the respiratory failure had worsened withdevelopment of multiple organ dysfunction (acute renal failure and thrombocytopenia; serumbilirubin and amylase levels remained normal). In addition, inflammatory markers haddeteriorated together with the reappearance of cardiovascular instability. On day 13 ofmechanical ventilation, a thoracic CT scan showed diffuse bilateral alveolar infiltrates withdilatation and distortion of bronchial structures. New alveolar infiltrates were seen in the left lung(Fig. 1) and bronchoscopic alveolar lavage (BAL) via the endotracheal tube was done.Postbronchoscopy VAP treatment was escalated, with re-initiation of vancomycin and empiricadministration of imipenem, fluconazole and amikacin. Analysis of BAL fluid for detection ofbacterial pathogens (by microscopy and culture) was negative, as were molecular detection testsfor influenza A and B and respiratory syncytial virus. BAL fluid was negative for hemosiderin-laden macrophages, excluding occult alveolar haemorrhage as a cause.Despite empiric antibiotics, and inotropic, vasopressor and ventilator support, the patientdeteriorated and died on the 20th postoperative day. The family refused permission for necropsy.After the patient’s death, analysis of stored BAL fluid showed the presence of P. jirovecii in singleforms or typical clusters (one every ten fields at 20 magnification), demonstrated by Grocott-Gomori methenamine silver stain (Fig. 2a), and by detection of Pneumocystis-specific DNA using asingle round polymerase chain reaction (PCR) using the oligonucleotide primers, pAZ102E andVentilator-associated pneumonia caused by Pneumocystis jirovecii 25pAZ102H, designed to detect the gene encoding the mitochondrial large subunit ribosomalribonucleic acid (LSU mt rRNA) gene of Pneumocystis spp.[5] (Fig. 2b).DiscussionThe patient described here meets the diagnostic criteria for VAP[1]. The clinical and radiologicalprogression while ventilated, the repeatedly negative results of bacterial culture of blood andendotracheal samples and demonstration of P. jirovecii in BAL fluid by histochemical staining andsingle round PCR strongly support the inference that Pneumocystis had a pathological role in thiscase. Cardiac and non-infectious pulmonary and extrapulmonary causes of ventilator-associatedpulmonary infiltrates were excluded.PCP as the cause of VAP in this patient probably represents progression from asymptomaticcolonization to clinical disease in the context of a critically ill immunocompromised patient aftercardiac surgery[6]. Cardiac surgery may induce immunosuppression; likely mechanisms includeactivation of anti-inflammatory cytokines, surgical trauma, reperfusion injury, and the effect ofcardiopulmonary bypass[7,8].The origin of P. jirovecii in this patient is difficult to ascertain. Person-to-person transmission ofP. jirovecii has been described in several inpatient and outpatient hospital clinical settings andperson-to-person transmission has been suggested among immunocompetent contacts of patientsFig. 2. (a) Bronchoscopic alveolar lavage specimen. Cluster of P. jirovecii cystic forms (centre). Grocott-Gomori methenaminesilver stain (magnification 40). (b) Products of DNA amplification displayed on an ethidium gel, using the Pneumocystis-specific oligonucleotide primers (pAZ102E and pAZ102H) applied to DNA extracted from BAL fluid from the patient. Key: L,1 kb molecular weight markers (sizes shown to the left of the column); IC, human -globin as internal control; NC, negativecontrol (with no added DNA template); Pt, patient; blank, one-fifth dilution of patient sample; PC, two P. jirovecii DNA-positive controls. The Pneumocystis-specific amplification product¼346 base pairs.Fig. 1. CT thorax performed after 13 days of mechanical ventilation, showing diffuse bilateral alveolar infiltrates with areasof ground-glass opacity, and dilatation and distortion of bronchial structures.26 E. Tobar et al.with PCP[9,10]. However, the slow growth rate of Pneumocystis makes it unlikely that this caserepresents a nosocomial infection acquired from another patient during her brief hospitaliza-tion[11]. In addition, no other patients with PCP were contemporaneously diagnosed in thehospital. Asymptomatic infection with P. jirovecii is common in the general population and therole of these persons as an infective reservoir is possible[12,13].Pneumocystis jirovecii has previously been described as a cause of VAP[2,4,14]. Among 35 cases ofVAP occurring in 2167 patients after cardiac surgery, fungi accounted for 15 episodes; of thesetwo were due to P. jirovecii[2]. Puzio et al.[4] described 27 patients from a cohort of 5026 who hadundergone cardiac surgery and who developed prolonged respiratory failure requiring mechanicalventilation in whom atypical or opportunistic pathogens were identified. P. jirovecii was identifiedin 17/27 patients (together with C. pneumoniae in three patients (one of whom also had M.pneumonia)). Another study described VAP caused by P. jirovecii in five elderly patients (age 71–93 years)[14]. Although our patient shares a history of cardiac surgery with these studies, bycontrast our patient had no underlying medical condition, and was not taking corticosteroids orother immune suppressive drugs. In the study by Puzio et al.[4], the significance of identifying P.jirovecii in tracheal aspirates is uncertain, as 7/27 patients had a normal chest radiograph, 10 hadunderlying chronic lung disease and 4 were immunosuppressed because they had undergoneheart or lung transplantation. All five elderly patients described by Yu and Sun[14] had cancer orwere receiving corticosteroid therapy.P. jirovecii as a cause of VAP is extremely rare, and thus it should be considered in cases withhighly suggestive thoracic CT imaging and/or negative bacterial cultures of BAL fluid.Teaching points This case highlights the emerging importance of unusual pathogens, including P. jirovecii, inthe pathogenesis of VAP in non-neutropenic, non-lymphopenic critically unwell, HIV-uninfected patients undergoing cardiac surgery. Clinicians should be alert to the potential for atypical and opportunistic organisms to causeVAP in the postoperative period, especially among patients with prolonged respiratorycompromise and a need for mechanical ventilation.AcknowledgementsThis work was supported in part by the Chilean Fund for Science and Technology (Fondecyt)grants 11100246 (ET) and 1100225 (SLV).References1. Valencia M, Torres A. Ventilator-associated pneumonia. Curr Opin Crit Care 2009; 15: 30–35.PMid:19186407.2. Serban RI, Dan M, Paˆnzaru CV, et al. Etiology of ventilator-associated pneumonia at the cardio-vascular surgery clinic of Ias i. Rev Med Chir Soc Med Nat Ias i 2012; 116: 15–21.3. Serban RI, Dan M, Paˆnzaru CV, et al. Fungi as emergent etiologic agents in ventilator-associated pneumonia after cardiac surgery. Rev Med Chir Soc Med Nat Ias i 2010; 114:1077–1082.4. Puzio J, Kucewicz E, Siola M, et al. Atypical and opportunistic pulmonary infections aftercardiac surgery. Anestezjol Intens Ter 2009; 41: 41–45. PMid:19517677.5. Wakefield AE, Miller RF, Guiver LA, Hopkin JM. Oropharyngeal samples for detection ofPneumocystis carinii by DNA amplification. Q J Med 1993; 86: 401–406. PMid:8171187.6. Monneret G, Venet F, Kullberg BJ, Netea MG. ICU-acquired immunosuppression andthe risk for secondary fungal infections. Med Mycol 2011; 49(Suppl 1): S17–23.PMid:20718607.7. Yeh CH, Cheng BC, Hsu CC, et al. Induced interleukin-19 contributes to cell-mediatedimmunosuppression in patients undergoing coronary artery bypass grafting with cardiopul-monary bypass. Ann Thorac Surg 2011; 92: 1252–1259. PMid:21855850.8. Franke A, Lante W, Kackeldey V, et al. Pro-inflammatory cytokines after different kinds ofcardio-thoracic surgical procedures: is what we see what we know?. Eur J Cardiothoracic Surg2005; 28: 569–575.Ventilator-associated pneumonia caused by Pneumocystis jirovecii 279. Schmoldt S, Schuhegger R, Wendler T, et al. Molecular evidence of nosocomial Pneumocystisjirovecii transmission among 16 patients after kidney transplantation. J Clin Microbiol 2008;46: 966–971. PMid:18216217.10. Gianella S, Haeberli L, Joos B, et al. Molecular evidence of interhuman transmission in anoutbreak of Pneumocystis jirovecii pneumonia among renal transplant patients. Transpl InfectDis 2010; 12: 1–10. PMid:19744285.11. Aliouat el-M, Dujardin L, Marinez A, Duriez T, Ricard I, Dei-Cas E. Pneumocystis carinii growthkinetics in culture systems and in hosts: involvement of each life cycle parasite stage. JEukaryot Microbiol 1999; 46: 116S–117S.12. Medrano FJ, Montes-Cano M, Conde M, et al. Pneumocystis jirovecii in the general population.Emerg Infect Dis 2005; 11: 245–250. PMid:15752442.13. Ponce CA, Gallo M, Bustamante R, Vargas SL. Pneumocystis colonization is highly prevalent inthe autopsied lungs of the general population. Clin Infect Dis 2010; 50: 347–353.PMid:20047487.14. Yu SY, Sun BJ. Ventilator-associated pneumonia caused by Pneumocystis carinii in the non-human immunodeficiency virus infection: a report of 5 cases. Zhonghua Nei Ke Za Zhi 2004;43: 654–656. PMid:15500775.28 E. Tobar et al.

Ventilator-associated Pneumonia After Elective Cardiac Surgery Caused by Pneumocystis Jirovecii

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Ventilator-associated Pneumonia After Elective Cardiac Surgery Caused by Pneumocystis Jirovecii

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