CASE REPORT

Fulminant Mycoplasmapneumoniae PneumoniaYasuo Takiguchi, Nobuaki Shikama, Nobuyuki Aotsuka, Hideyuki Koseki,

Takashi Terano and Akira Hirai

Abstract

A 64-year-old womanwho was previously in good healthwas admitted because of progressive respiratory distress.Her chest radiograph revealed bilateral widespread alveo-lar infiltrates. She was given a diagnosis of pneumoniacaused by Mycoplasmapneumoniaeserologically, acute res-piratory distress syndrome, and disseminated intravas-cular coagulation. She died of multiple organ failure de-spite intensive therapy with mechanical ventilation, intra-venous erythromycin and corticosteroids, continuoushemodiafiltration, and plasma exchange. Although Myco-plasma pneumoniae infection is usually a benign self-lim-ited disease, this case emphasizes its potentially seriousnature even in normal healthy individuals.(Internal Medicine 40: 345-348, 2001)

Key words: acute respiratory distress syndrome, multiple or-gan failure, disseminated intravascular coagulation

Introduction

Mycoplasmapneumoniae (M pneumoniae) pneumonia is acommunity-acquired infection occurring primarily in childrenand young adults, and is usually a benign self-limited disease(1), however, some cases are knownto develop a severe life-threatening pneumonia with acute respiratory failure (2-7). M.pneumoniae has been implicated as a cause of respiratory in-fection, sometimes producing a wide variety of non-respira-tory symptoms, such as neurologic, dermatologic, gastrointes-tinal, hematologic, cardiovascular, musculoskeletal, and renalsystem.

Wereport a case of fatal pneumoniacaused by M. pneu-moniae with acute respiratory distress syndrome, disseminatedintravascular coagulation, and multiple organ failure.

Case ReportA 64-year-old womanwho was previously in good health

experienced cough and fever on November 15, 1999. She wasnonsmoker. Her symptomspersisted, and she was admitted toanother hospital on November 27. Chest radiograph revealedalveolar infiltrates of the left lower lobe. The white blood cellcount was 9, 100/mm3, C-reactive protein 3 1.0 mg/dl, aspartateaminotransferase 1 37 IU//, alanine aminotransferase 1 05 IU//,and lactate dehydrogenase 9 16 IU//; and indirect hemaggluti-nation titer for M. pneumoniae (Fujirebio Inc. Japan) was 1 :160. Sputum and blood culture were not performed. Althoughoral (levofloxacin 300 mg daily) and intravenous (cefotiamhydrochloride 2 g daily, ceftazidime 2 g daily) antibiotics wereadministrated, her condition worsened and dyspnea on effortdeveloped. She was transferred to our intensive care unit be-cause of diffuse pulmonary infiltrates and respiratory failureon December 2, 1999.She was confused, with a temperature of 36.6°C, pulse of140 per minute, respiration rate of 30 per minute, and bloodpressure of 140/82 mmHg.On physical examination, the headand neck were normal. There was no lymphadenopathy. Dif-fuse bilateral inspiratory crackles were heard, systolic murmurwas not audible. Examination of the abdomenand neurologicsystem were unremarkable. Chest radiograph (Fig. 1 ) and com-puted tomography revealed widespread alveolar infiltratesinvolving both lung fields. Although 100% oxygen was ad-ministered by face mask, her oxygen saturation did not rise.The trachea was intubated and ventilatory support began. Dur-ing assisted ventilation with 100% oxygen, arterial bloodshowed a pH of7.308, PaO2 of 37.2 mmHg, and PaCO2 of51.3 mmHg.The peripheral white blood cell count was 10, 500/mm3 with92% neutrophils, hemoglobin 13.5 g/dl, platelet count 3 1.7x 104/mm3, and C-reactive protein 1 3.7 mg/dl. The prothrombin timewas ll.3 seconds, with a control of 10.1 seconds; the partialthromboplastin time was 35.2 seconds, with a control of 32.9seconds. The fibrin/fibrinogen degradation product was 40-80lig/ml. Urea nitrogen was 17.3 mg/dl, creatinine 0.7 mg/dl,glucose 170 mg/dl, protein 4.6 g/dl, and albumin 2.1 g/dl. So-dium was 131 mmol, potassium 4.6 mmol, and chloride 92mmol. Serum aspartate aminotransferase was 108 IU//, ala-nine aminotransferase 46 IU//, alkaline phosphatase 355 IU//,and lactate dehydrogenase 1,115 IU//. The urine was + posi-

From the Department of Internal Medicine, Chiba Municipal Hospital, ChibaReceived for publication May 3 1 , 2000; Accepted for publication October 3, 2000Reprint requests should be addressed to Dr. Yasuo Takiguchi, the Department of Internal Medicine, Chiba Municipal Hospital, 827, Yahagi, Chuo-ku, Chiba

260-0851

Internal Medicine Vol. 40, No. 4 (April 2001) 345

Takiguchi et al

Figure 1. Chest radiograph on admission showing alveolar in-filtrates in both lung fields.

tive for protein; the sediment contained many casts per high-powerfield. Smearand routine culture of sputum was negativefor bacteria and mycobacteria except for a-streptococcus. Bloodculture was sterile.Later in the day, while the patient was receiving ventilationwith 100% oxygen on intermittent mandatory ventilation of 1 8breaths per minute and a positive end-expiratory pressure of 5cmH20, her arterial blood showed a pH of7.393, PaO2 of44.8mmHg, and PaCO2 of 42.7 mmHg. Erythromycin (3 g daily),panipenem/betamipron ( 1.5 g daily) and methylprednisolone(0.5 g daily) were administered empirically.The indirect hemagglutination titer for M. pneumoniae was1 : 5,120. Polymerase chain reaction test for M. pneumoniae(National Institute of Infectious Diseases original method) ofaspiration sample from the bronchus was also positive. Thecold-agglutinin titer was not tested. Serologic titer for Chlamy-dia psittaci and Legionella pneumophila (serogroup 1) werenegative. Serologic titer for Chlamydia pneumoniae IgA andIgG index were 1. 137 and 1. 193, respectively. Echo cardiogra-phy revealed moderate mitral and tricuspid insufficiency, how-ever, cardiac function of the left ventricle was within normallimits. Diagnosis of bilateral pneumonia due to M pneumoniaeand acute respiratory distress syndromewere confirmed. Onthe 2nd hospital day, her C-reactive protein was elevated and

the platelet count dropped. The fibrin/fibrinogen degradationproduct was 80-160 |ig/ml. Treatment with intravenous eryth-romycin, panipenem/betamipron, and methyl-prednisolone

(500 mg daily) were continued. Minocycline (0.3 g daily) andgabexate mesilate (2 g daily) were administered in addition tothese drugs. On the 3rd hospital day, the urea nitrogen and crea-tinine level became elevated to 53.1 mg/dl and 3.1mg/dl, re-

spectively. Venipuncture oozing emerged on her skin. Onthe6th hospital day, she was anuric and the urea nitrogen and thecreatinnne levels were further elevated to 144.5 mg/dl and 6.0mg/dl, respectively. Continuoushemodiafiltration was started.Despite this therapy, direct bilirubin and lactate dehydroge-nase, isozyme 5 were predominantly, elevated. On the 7th hos-pital day, the hemoglobin and platelet count dropped consider-ably to 7.4 g/dl and 4.2xlO4/mm3, respectively. Red blood celland platelet concentrates were transfused to support hemoglo-bin and platelet count levels after the 8th hospital day. Further-more, plasma exchange (fresh frozen plasma 30 units daily)was began on the 9th hospital day. The chest X-ray revealedclearing of the infiltrate, especially in both lower lung fields.C-reactive protein, lactate dehydrogenase, direct bilirubin, ureanitrogen, and creatinine dropped transiently. On the 14th hos-pital day, the white blood cell count, C-reactive protein, and p-Dglucan were elevated again. Cultures of sputum and bloodgrew Candida albicans. Fluconazole (300 mg daily) was started.In spite of treatment, she died of multiple organ failure on De-cember 18, 1999. Figure 2 shows her clinical course.

Discussion

Since the first report of fatal M. pneumoniae infection (2),manysevere cases have been reported. In the previous reviewsof fatal M. pneumoniae infection, death has generally been dueto diffuse pneumonia, adult respiratory distress syndrome, vas-cular thrombosis and disseminated intravascular coagulation(3-9). Koletsky and Weinstein (3) reviewed eleven fatal casesof M. pneumoniae infection; all but one of the patients hadpneumonia. Vascular thrombosis, usually associated with inf-arction, in sites such as the lung, spleen, kidney, and brain de-veloped in five patients. Chan and Welsh (4) reviewed cases ofM. pneumoniaepneumonia that have resulted in respiratoryfailure or death, and emphasized that fluminant cases seem tobe more commonin young healthy adults, in males, and possi-bly in smokers. Fraley et al (5) noted that pleural effusion, leu-kocytosis, and high titer cold agglutinins seem to be character-istic of more severe patients.M. pneumoniae infection is rarely complicated by dissemi-nated intravascular coagulation and multiple organ failure (3,4, 8, 9). In this case, it may be possible that hepato-renal dys-function was drug-induced, however, the lactate dehydroge-nase and the fibrin/fibrinogen degradation product were alreadyelevated on admission. Wesuspect that M. pneumoniae pneu-monia was complicated by multiple organ failure. Recently, ithas been reported that continuous hemodiafiltration and plasmaexchange are useful in the treatment of multiple organ failure(10, 1 1). Although she received this therapy, she finally died.

346 Internal Medicine Vol. 40, No. 4 (April 2001)

Fulminant MycoplasmaPneumonia

m-PSL0.5g PSLGOmg 40mg ' 2Qmg |

EM3g l 2g -|

~" PAPM1.5g| 1 PAPMlg

I MINO 0.3 g I [^cz °-3 «WBC CRP ' å (/mm3) (mg/dl) < Continuous hemodiafiltration ^

25,000-l 30-1 CT?P ^ Plasmaexchange ^

oJ oJT-Bil LDH(mg/dl) (IU//)10-i 6,000-t

0J o-J

BUN CRE(mg/dl) (mg/dl)

0J o-J-i 1 1 . 1 j 1 ,

Dec 2 Dec 4 Dec 6 Dec 8 Dec 10 Dec 12 Dec 14 Dec 16

Figure 2. Clinical course. m-PSL: methylprednisolone, PSL: prednisolone, EM: erythromycin, PAPM:panipenem/betamipron,MINO: minocycline, FLCZ: fluconazole, WBC: white blood cell count, CRP: C-reactive protein, T-Bil: total bilirubin, LDH:lactate dehydrogenase, BUN:blood urea nitrogen, CRE: creatinine.

Corticosteroids have been used and indeed advocated fordecreasing the inflammatory response and improving survival(4-6). Noriega et al (6) suggested that the host's cellular im-mune response to M. pneumoniae played a central role in se-vere pneumonitis. They postulated that previously sensitizedlymphocytes from an earlier infection are activated during asubsequent infection and release supranormal levels of media-tors that cause local tissue damage, and that the use of corti-costeroids, in addition to specific antibiotic therapy, maybeadvantageous. Foy et al (12) reported M. pneumoniae patientswith immunodeficiency syndromes, and found that clinicallysevere patients with immunodeficiency syndromes had no sig-nificant pulmonary infiltrates. Thus, the host's immune responsemaybe an essential factor in the production of the pulmonaryinfiltrates. The reports support the hypothesis that fulminantM. pneumoniae infection is associated with an excessive im-muneresponse. Therefore these hypotheses support steroidtherapy for severe M. pneumoniae infections.

The diagnosis was confirmed on the 2nd hospital day andimmediately administration of intravenous erythromycin andcorticosteroids was started. In spite of this early treatment, she

died. Although we could not isolate any organisms other thanM. pneumoniae in sputum cultures, there was a possibility ofmixed infection with M. pneumoniae and other pathogens. In

this case, she had not been administrated antibiotics which areactive against M. pneumoniae, and her condition worsened.Wesuspect the cause of multiple organ failure was M.pneumoniae. This case emphasizes the potentially serious na-ture of this infection even in normal healthy individuals.

Acknowledgements: Wegratefully acknowledge the assistance of Kori Y.and Suruga Y. in our hospital, and we would like to thank the National Instituteof Infectious Diseases for performing the polymerase chain reaction test forM. pneumoniae.

Internal Medicine Vol. 40, No. 4 (April 2001) 347

Takiguchi et al

Reference

1) Mansel JK, Rosenow III EC, Smith TF, Martin JW Jr. Mycoplasmapneumoniae pneumonia. Chest 95: 639-646, 1989.2) Maisel JC, Babbitt LH, John TJ. Fatal Mycoplasma pneumoniae infec-tion with isolation of organisms from lung. JAMA 202: 287-290, 1967.3) Koletsky RJ, Weinstein AJ. Fulminant Mycoplasma pneumoniae infec-tion. Report of a fatal case, and review of the literature. AmRev Respir

Dis 122: 491-496, 1980.

4) Chan ED, Welsh CH. Fulminant Mycoplasma pneumoniae pneumonia.West J Med 162: 133-142, 1995.

5) Fraley DS, Ruben FL, Donnelly EJ. Respiratory failure secondary toMycoplasma pneumoniae infection. South Med J 72: 437-440, 1979.6) Noriega ER, Simberkoff MS, Gilroy FJ, Rahal JJ Jr. Life-threateningMycoplasma pneumoniae pneumonia. JAMA229: 1471-1472, 1974.7) Fischman RA, Marschall KE, Kislak JW, Greenbaum DM. Adult respira-

tory distress syndrome caused by Mycoplasma pneumoniae. Chest 74:471-473, 1978.

8) Nilsson IM, Rausing A, Denneberg T, Christensson P. Intravascular co-agulation and acute renal failure in a child with Mycoplasma infection.Acta Med Scand 189: 359-365, 1971.

9) De Vos M, Van Nimmen L, Baele G. Disseminated intravascular coagula-tion during a fatal Mycoplasmapneumoniae infection. Acta Haematol

52: 120-125, 1974.

10) McClelland P, Williams PS, Yaqoob M, Mostafa SM, Bone JM. Multipleorgan failure -A role for plasma exchange? Intensive Care Med 16: 100-

103, 1990.

1 1) Hirasawa H, Sugai T, Ohtake Y, et al. Continuous hemofiltration andhemodiafiltration in the management of multiple organ failure. ContribNephrol 93: 42-46, 1991.

12) Foy HM, Ochs H, Davis SD, Kenny GE, Luce RR. Mycoplasmapneumoniae infections in patients with immunodeficiency syndromes:report of four cases. J Infect Dis 127: 388-393, 1973.

348 Internal Medicine Vol. 40, No. 4 (April 2001)