- Email: [email protected]
A 51-Year-Old Man Presenting With Shock and Lower-Lobe Consolidation With Interlobar Bulging Fissure
CHEST
Postgraduate Education Corner PULMONARY, CRITICAL CARE, AND SLEEP PEARLS
A 51-Year-Old Man Presenting With Shock and Lower-Lobe Consolidation With Interlobar Bulging Fissure Cedric Rafat, MD; Vincent Fihman, PharmD, PhD; and Jean-Damien Ricard, MD, PhD
CHEST 2013; 143(4):1167–1169
white man was referred to our departA51-year-old ment for acute onset of dyspnea, fever, productive
cough, and purulent sputum. His past medical history was remarkable for tobacco addiction and alcohol abuse. He did not report having diabetes and denied having traveled overseas. Physical Examination Findings On admission, physical examination revealed signs of septic shock with mild hypothermia (35°C), hypotension (BP, 90/70 mm Hg) unresponsive to fluid loading, tachycardia (heart rate, 130 beats/min), cold extremities, and mottling. Pulmonary examination was remarkable for respiratory distress with tachypnea (respiratory rate, 40 breaths/min), right basal crackles, and an oxygen saturation of 90% with 9 L/min oxygen. The remainder of his physical examination was unremarkable. Diagnostic Studies Notable laboratory findings included leukopenia with a total leukocyte count of 2.2 3 103 mL, and thromManuscript received August 11, 2012; revision accepted August 30, 2012. Affiliations: From the Service de Réanimation Médico-Chirurgicale (Drs Rafat and Ricard) and Laboratoire de Microbiologie-Hygiène (Dr Fihman), Assistance Publique-Hôpitaux de Paris, LouisMourier, Hôpitaux Universitaires Paris Nord Val de Seine, Colombes; Sorbonne Paris Cité (Dr Ricard), Université Paris Diderot, Unité Mixte de Recherche en Santé U722, Paris; and Institut national de la santé et de la recherche médicale (Dr Ricard), INSERM U722, Paris, France. Correspondence to: Cedric Rafat, MD, Service de Réanimation Médico-Chirurgicale, Louis-Mourier, Hôpitaux Universitaires Paris Nord Val de Seine, 178 rue des Renouillers 92701 Colombes, France; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.12-2007
Figure 1. CT scan of the thorax showing a right lower-lobe consolidation with interlobar bulging fissure.
bocytopenia with a platelet count of 83 3 10 3/mL. A serum chemistry test showed lactate acidosis with a lactic acid level of 10.7 mmol/L and acute renal failure with a blood urea nitrogen level of 11 mmol/L and a serum creatinine level of 2.4 mg/dL. Liver enzyme plasma levels were normal. Blood gas measurements performed on room air showed severe hypoxemia and metabolic acidosis. A thoracic chest CT scan revealed right basal lung consolidation along with a bulging interlobar fissure (Fig 1). Direct examination of sputum obtained by tracheobronchial aspiration, performed immediately following intubation, yielded Gram-negative bacilli. What is the diagnosis?
journal.publications.chestnet.org
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 04/04/2013
CHEST / 143 / 4 / APRIL 2013
1167
Diagnosis: Septic shock due to community-acquired pneumonia caused by hypermucoviscous Klebsiella pneumoniae
Discussion K pneumoniae (Kp) is a Gram-negative member of the Enterobacteriaceae family, recognized 100 years ago as a potential cause of community-acquired pneumonia (CAP). However, in the Western world, CAP due to Kp remains an uncommon entity and accounts for , 3% of the total CAP cases. Common findings on chest CT scan assessment in patients presenting with acute CAP related to Kp infection include ground-glass opacities, consolidation, intralobular reticular opacities, and pleural effusion, albeit none of these abnormalities are specifically related to this microorganism. Historically regarded to be suggestive of Kp infection, the presence of a bulging fissure is thought to be the consequence of the large amounts of inflammatory exudates resulting in the displacement of the contiguous interlobar fissure. However, the bulging fissure sign is not pathognomonic of Kp pneumonia since it has been occasionally described in cases of pulmonary infections due to Streptococcus pneumoniae, Legionella pneumophila, Haemophilus influenzae, Mycobacterium tuberculosis, and Yersinia pestis. Moreover, there seems to be a distinction between nosocomial Kp pneumonia, a setting in which the bulging fissure sign is absent, and Kp infection of the community-acquired variety in which the bulging fissure sign occurs in approximately 50% of the patients. Over the past 10 years, alongside the worldwide emergence of extended-spectrum b-lactamase, both in hospital and community setting, there has been a growing number of reports regarding a clinical syndrome related to hypermucoviscous Kp (hKp) causing severe community-acquired infections with a propensity for pneumonia, bacteremia, liver abscesses, and other sites of metastatic infection. Ever since its first description in Taiwan in the mid-1980s, this unique Kp-related clinical pattern has fueled numerous studies arising primarily from cases of Asian patients with liver abscess. In addition to infectious liver disease, hKp displays a remarkable ability to disseminate, causing a wide range of systemic infections, including CAP, meningitis, endophthalmitis, or urinary tract infections. The link between the hypermucoviscous phenotype of the bacteria and its invasive propensity has been established. It has been postulated that this phenotype could promote the bacteria’s resistance to phagocytosis, thereby enhancing its virulence. In addition, the hKp strain can also harbor K2-specific sequences and rmpA virulence
factor both of which have been associated with the hypermucoviscous phenotype and fatal bacteremic hKp infection. Furthermore, Kp can also express ybtS, another pivotal virulence factor which has been shown to be intimately associated with respiratory infections. Although tobacco smoking and alcohol abuse are well-recognized risk factors for Kp pneumonia, strikingly, in this case, none of the usual risk factors described in the setting of hKp pneumonia were found, namely diabetes, Asian ancestry, or recent travel in Asia. Why Asian patients are more susceptible to hKp remains to be determined and although a host-pathogen interplay has been evoked, compelling evidence to substantiate this hypothesis is lacking. This case illustrates that hKp may well be no longer limited by such ethnic or geographical determinants. Finally, another salient feature in hKp infections is its resistance pattern, usually restricted to ticarcillin and ampicillin, a reminder that the future challenges when dealing with Kp infections may not only lie in its extended spectrum b-lactamase-producing phenotype. Clinical Course The patient was started on combined therapy by cefotaxime, spiramycin, and gentamicin. Initial management of septic shock consisted of mechanical ventilation, aggressive fluid loading, and vasopressor support. The patient’s clinical condition deteriorated rapidly and, within 2 h following admission, the patient developed ARDS and multiorgan failure, prompting neuromuscular blockade, prone positioning, and corticosteroid administration. Despite these measures, the patient progressed to refractory shock and died 12 h after admission.
Figure 2. Hypermucoviscous phenotype of Klebsiella pneumoniae suggested by the formation of a viscous string . 10 mm in length when the colony was stretched with a standard bacteriologic loop.
1168
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 04/04/2013
Postgraduate Education Corner
Blood and sputum cultures confirmed the presence of an hKp strain with a positive string test (Fig 2) and its usual resistance pattern. Upon further microbiologic testing, the Kp strain was positive for mucoidspecific sequence (rmpA), K2 wzy-specific sequences, and yersiniabactin-related siderophore (ybtS). Other virulence factors were absent (magA, allS). Clinical Pearls 1. The occurrence of a bulging interlobular fissure sign on chest imaging is evocative of Kp pulmonary infection. 2. hKp can cause a myriad of infectious syndromes among which CAP, septicemia, and liver abscess rank among the most prominent. 3. hKp infections are no longer confined to Southeastern Asian patients and should be regarded as an emerging disease in the Western world. 4. Usual risk factors for Kp CAP, including substance abuse, may not be applicable in the setting of hKp CAP. 5. Confronted with hKp CAP, attending physicians should be aware that a fulminant clinical course with septic shock and multiorgan failure is of frequent occurrence. 6. A string test can reliably identify hKp strains, which harbor its usual resistance pattern. Molecular biology techniques have unveiled the existence of virulence factors connected to both the respiratory tropism and to severe clinical presentation. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Other contributions: The authors obtained permission from the patient’s family to publish this information. The authors express their gratitude to Drs Dominique Decré, PharmD, PhD; Stéphane Gaudry, MD; and Léopold Oliver, resident in medicine, for their critical review of the work.
Suggested Readings Korvick JA, Hackett AK, Yu VL, Muder RR. Klebsiella pneumonia in the modern era: clinicoradiographic correlations. South Med J. 1991;84(2):200-204. Moon WK, Im JG, Yeon KM, Han MC. Complications of Klebsiella pneumonia: CT evaluation. J Comput Assist Tomogr. 1995;19(2): 176-181. Ko WC, Paterson DL, Sagnimeni AJ, et al. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis. 2002;8(2):160-166. Fang CT, Chuang YP, Shun CT, Chang SC, Wang JT. A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med. 2004;199(5):697-705. Lee HC, Chuang YC, Yu WL, et al. Clinical implications of hypermucoviscosity phenotype in Klebsiella pneumoniae isolates: association with invasive syndrome in patients with communityacquired bacteraemia. J Intern Med. 2006;259(6):606-614. Keynan Y, Rubinstein E. The changing face of Klebsiella pneumoniae infections in the community. Int J Antimicrob Agents. 2007;30(5):385-389. Okada F, Ando Y, Honda K, et al. Clinical and pulmonary thinsection CT findings in acute Klebsiella pneumoniae pneumonia. Eur Radiol. 2009;19(4):809-815. Ruiz LA, Gómez A, Jaca C, Martínez L, Gómez B, Zalacain R. Bacteraemic community-acquired pneumonia due to Gramnegative bacteria: incidence, clinical presentation and factors associated with severity during hospital stay. Infection. 2010; 38(6):453-458. Bachman MA, Oyler JE, Burns SH, et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect Immun. 2011;79(8):3309-3316. Decré D, Verdet C, Emirian A, et al. Emerging severe and fatal infections due to Klebsiella pneumoniae in two university hospitals in France. J Clin Microbiol. 2011;49(8):3012-3014. Wu HS, Wang FD, Tseng CP, Wu TH, Lin YT, Fung CP. Characteristics of healthcare-associated and community-acquired Klebsiella pneumoniae bacteremia in Taiwan. J Infect. 2012;64(2): 162-168.
journal.publications.chestnet.org
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 04/04/2013
CHEST / 143 / 4 / APRIL 2013
1169
Postgraduate Education Corner PULMONARY, CRITICAL CARE, AND SLEEP PEARLS
A 51-Year-Old Man Presenting With Shock and Lower-Lobe Consolidation With Interlobar Bulging Fissure Cedric Rafat, MD; Vincent Fihman, PharmD, PhD; and Jean-Damien Ricard, MD, PhD
CHEST 2013; 143(4):1167–1169
white man was referred to our departA51-year-old ment for acute onset of dyspnea, fever, productive
cough, and purulent sputum. His past medical history was remarkable for tobacco addiction and alcohol abuse. He did not report having diabetes and denied having traveled overseas. Physical Examination Findings On admission, physical examination revealed signs of septic shock with mild hypothermia (35°C), hypotension (BP, 90/70 mm Hg) unresponsive to fluid loading, tachycardia (heart rate, 130 beats/min), cold extremities, and mottling. Pulmonary examination was remarkable for respiratory distress with tachypnea (respiratory rate, 40 breaths/min), right basal crackles, and an oxygen saturation of 90% with 9 L/min oxygen. The remainder of his physical examination was unremarkable. Diagnostic Studies Notable laboratory findings included leukopenia with a total leukocyte count of 2.2 3 103 mL, and thromManuscript received August 11, 2012; revision accepted August 30, 2012. Affiliations: From the Service de Réanimation Médico-Chirurgicale (Drs Rafat and Ricard) and Laboratoire de Microbiologie-Hygiène (Dr Fihman), Assistance Publique-Hôpitaux de Paris, LouisMourier, Hôpitaux Universitaires Paris Nord Val de Seine, Colombes; Sorbonne Paris Cité (Dr Ricard), Université Paris Diderot, Unité Mixte de Recherche en Santé U722, Paris; and Institut national de la santé et de la recherche médicale (Dr Ricard), INSERM U722, Paris, France. Correspondence to: Cedric Rafat, MD, Service de Réanimation Médico-Chirurgicale, Louis-Mourier, Hôpitaux Universitaires Paris Nord Val de Seine, 178 rue des Renouillers 92701 Colombes, France; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.12-2007
Figure 1. CT scan of the thorax showing a right lower-lobe consolidation with interlobar bulging fissure.
bocytopenia with a platelet count of 83 3 10 3/mL. A serum chemistry test showed lactate acidosis with a lactic acid level of 10.7 mmol/L and acute renal failure with a blood urea nitrogen level of 11 mmol/L and a serum creatinine level of 2.4 mg/dL. Liver enzyme plasma levels were normal. Blood gas measurements performed on room air showed severe hypoxemia and metabolic acidosis. A thoracic chest CT scan revealed right basal lung consolidation along with a bulging interlobar fissure (Fig 1). Direct examination of sputum obtained by tracheobronchial aspiration, performed immediately following intubation, yielded Gram-negative bacilli. What is the diagnosis?
journal.publications.chestnet.org
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 04/04/2013
CHEST / 143 / 4 / APRIL 2013
1167
Diagnosis: Septic shock due to community-acquired pneumonia caused by hypermucoviscous Klebsiella pneumoniae
Discussion K pneumoniae (Kp) is a Gram-negative member of the Enterobacteriaceae family, recognized 100 years ago as a potential cause of community-acquired pneumonia (CAP). However, in the Western world, CAP due to Kp remains an uncommon entity and accounts for , 3% of the total CAP cases. Common findings on chest CT scan assessment in patients presenting with acute CAP related to Kp infection include ground-glass opacities, consolidation, intralobular reticular opacities, and pleural effusion, albeit none of these abnormalities are specifically related to this microorganism. Historically regarded to be suggestive of Kp infection, the presence of a bulging fissure is thought to be the consequence of the large amounts of inflammatory exudates resulting in the displacement of the contiguous interlobar fissure. However, the bulging fissure sign is not pathognomonic of Kp pneumonia since it has been occasionally described in cases of pulmonary infections due to Streptococcus pneumoniae, Legionella pneumophila, Haemophilus influenzae, Mycobacterium tuberculosis, and Yersinia pestis. Moreover, there seems to be a distinction between nosocomial Kp pneumonia, a setting in which the bulging fissure sign is absent, and Kp infection of the community-acquired variety in which the bulging fissure sign occurs in approximately 50% of the patients. Over the past 10 years, alongside the worldwide emergence of extended-spectrum b-lactamase, both in hospital and community setting, there has been a growing number of reports regarding a clinical syndrome related to hypermucoviscous Kp (hKp) causing severe community-acquired infections with a propensity for pneumonia, bacteremia, liver abscesses, and other sites of metastatic infection. Ever since its first description in Taiwan in the mid-1980s, this unique Kp-related clinical pattern has fueled numerous studies arising primarily from cases of Asian patients with liver abscess. In addition to infectious liver disease, hKp displays a remarkable ability to disseminate, causing a wide range of systemic infections, including CAP, meningitis, endophthalmitis, or urinary tract infections. The link between the hypermucoviscous phenotype of the bacteria and its invasive propensity has been established. It has been postulated that this phenotype could promote the bacteria’s resistance to phagocytosis, thereby enhancing its virulence. In addition, the hKp strain can also harbor K2-specific sequences and rmpA virulence
factor both of which have been associated with the hypermucoviscous phenotype and fatal bacteremic hKp infection. Furthermore, Kp can also express ybtS, another pivotal virulence factor which has been shown to be intimately associated with respiratory infections. Although tobacco smoking and alcohol abuse are well-recognized risk factors for Kp pneumonia, strikingly, in this case, none of the usual risk factors described in the setting of hKp pneumonia were found, namely diabetes, Asian ancestry, or recent travel in Asia. Why Asian patients are more susceptible to hKp remains to be determined and although a host-pathogen interplay has been evoked, compelling evidence to substantiate this hypothesis is lacking. This case illustrates that hKp may well be no longer limited by such ethnic or geographical determinants. Finally, another salient feature in hKp infections is its resistance pattern, usually restricted to ticarcillin and ampicillin, a reminder that the future challenges when dealing with Kp infections may not only lie in its extended spectrum b-lactamase-producing phenotype. Clinical Course The patient was started on combined therapy by cefotaxime, spiramycin, and gentamicin. Initial management of septic shock consisted of mechanical ventilation, aggressive fluid loading, and vasopressor support. The patient’s clinical condition deteriorated rapidly and, within 2 h following admission, the patient developed ARDS and multiorgan failure, prompting neuromuscular blockade, prone positioning, and corticosteroid administration. Despite these measures, the patient progressed to refractory shock and died 12 h after admission.
Figure 2. Hypermucoviscous phenotype of Klebsiella pneumoniae suggested by the formation of a viscous string . 10 mm in length when the colony was stretched with a standard bacteriologic loop.
1168
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 04/04/2013
Postgraduate Education Corner
Blood and sputum cultures confirmed the presence of an hKp strain with a positive string test (Fig 2) and its usual resistance pattern. Upon further microbiologic testing, the Kp strain was positive for mucoidspecific sequence (rmpA), K2 wzy-specific sequences, and yersiniabactin-related siderophore (ybtS). Other virulence factors were absent (magA, allS). Clinical Pearls 1. The occurrence of a bulging interlobular fissure sign on chest imaging is evocative of Kp pulmonary infection. 2. hKp can cause a myriad of infectious syndromes among which CAP, septicemia, and liver abscess rank among the most prominent. 3. hKp infections are no longer confined to Southeastern Asian patients and should be regarded as an emerging disease in the Western world. 4. Usual risk factors for Kp CAP, including substance abuse, may not be applicable in the setting of hKp CAP. 5. Confronted with hKp CAP, attending physicians should be aware that a fulminant clinical course with septic shock and multiorgan failure is of frequent occurrence. 6. A string test can reliably identify hKp strains, which harbor its usual resistance pattern. Molecular biology techniques have unveiled the existence of virulence factors connected to both the respiratory tropism and to severe clinical presentation. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Other contributions: The authors obtained permission from the patient’s family to publish this information. The authors express their gratitude to Drs Dominique Decré, PharmD, PhD; Stéphane Gaudry, MD; and Léopold Oliver, resident in medicine, for their critical review of the work.
Suggested Readings Korvick JA, Hackett AK, Yu VL, Muder RR. Klebsiella pneumonia in the modern era: clinicoradiographic correlations. South Med J. 1991;84(2):200-204. Moon WK, Im JG, Yeon KM, Han MC. Complications of Klebsiella pneumonia: CT evaluation. J Comput Assist Tomogr. 1995;19(2): 176-181. Ko WC, Paterson DL, Sagnimeni AJ, et al. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis. 2002;8(2):160-166. Fang CT, Chuang YP, Shun CT, Chang SC, Wang JT. A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med. 2004;199(5):697-705. Lee HC, Chuang YC, Yu WL, et al. Clinical implications of hypermucoviscosity phenotype in Klebsiella pneumoniae isolates: association with invasive syndrome in patients with communityacquired bacteraemia. J Intern Med. 2006;259(6):606-614. Keynan Y, Rubinstein E. The changing face of Klebsiella pneumoniae infections in the community. Int J Antimicrob Agents. 2007;30(5):385-389. Okada F, Ando Y, Honda K, et al. Clinical and pulmonary thinsection CT findings in acute Klebsiella pneumoniae pneumonia. Eur Radiol. 2009;19(4):809-815. Ruiz LA, Gómez A, Jaca C, Martínez L, Gómez B, Zalacain R. Bacteraemic community-acquired pneumonia due to Gramnegative bacteria: incidence, clinical presentation and factors associated with severity during hospital stay. Infection. 2010; 38(6):453-458. Bachman MA, Oyler JE, Burns SH, et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect Immun. 2011;79(8):3309-3316. Decré D, Verdet C, Emirian A, et al. Emerging severe and fatal infections due to Klebsiella pneumoniae in two university hospitals in France. J Clin Microbiol. 2011;49(8):3012-3014. Wu HS, Wang FD, Tseng CP, Wu TH, Lin YT, Fung CP. Characteristics of healthcare-associated and community-acquired Klebsiella pneumoniae bacteremia in Taiwan. J Infect. 2012;64(2): 162-168.
journal.publications.chestnet.org
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 04/04/2013
CHEST / 143 / 4 / APRIL 2013
1169