| Abstract|| |
Staphylococcus aureus is a rare cause of pneumonia, though in recent times methicillin-resistant strains are emerging increasingly as causative pathogens. Methicillin resistant Staphylococcus aureus (MRSA) has been reported to cause rapidly fatal hemorrhagic pneumonia. Most of these strains have been found to produce a lethal exotoxin called Panton-Valentine leukocidin. The finding of an underlying asymptomatic multisystem sarcoidosis was unusual in the case being reported here.
Keywords: Methicillin resistant Staphylococcus aureus, pneumonia, sarcoidosis
|How to cite this article:|
Sirohi D, Sengupta P, Kumar H. Methicillin-resistant Staphylococcus pneumonia and underlying asymptomatic sarcoidosis: Are they related? A post-mortem case report. Indian J Pathol Microbiol 2010;53:297-301
|How to cite this URL:|
Sirohi D, Sengupta P, Kumar H. Methicillin-resistant Staphylococcus pneumonia and underlying asymptomatic sarcoidosis: Are they related? A post-mortem case report. Indian J Pathol Microbiol [serial online] 2010 [cited 2019 May 20];53:297-301. Available from: http://www.ijpmonline.org/text.asp?2010/53/2/297/64287
| Introduction|| |
Staphylococcus aureus is known for both community-acquired and hospital- acquired pneumonias, and when it does occur, it is the penicillin resistant strains that are commonly causative. Methicillin resistance Staphylococcus aureus (MRSA) has been reported both in community and hospital strains and is associated with rapidly fatal necrotizing pneumonias in young immunocompetent individuals. MRSA has emerged epidemiologically in a similar manner to penicillin resistance in the 1950s, occurring first in healthcare-associated settings then in the community. Initially, in the mid-1980s, hospital acquired MRSA (HA-MRSA) infections occurred most often in large hospitals and long-term care facilities. By the 1990s, smaller (<200 bed) community hospitals had MRSA prevalence rates of 20%, and twice this rate was present in larger urban medical centers.  In 2003, 60% of Staphylococcus aureus isolates in the ICU were resistant to methicillin.  HA-MRSA is usually associated with pneumonia, urinary tract, blood stream, and surgical wound infections. This is in contrast to community acquired MRSA (CA-MRSA) strains, which are overwhelmingly associated with skin and soft tissue infections. Its increase in the community is of concern because the CA-MRSA strains appear to be highly virulent, and colonization with CA-MRSA is often undetected in hospitalized patients, which can facilitate spread in the hospital and its potential for becoming resistant to multiple antibiotics. The emergence of CA-MRSA is also concerning in terms of absolute numbers of patients admitted to hospitals as a proportion of all MRSA hospital cases.
| Case Report|| |
The case presented is of a 26-year-old male in previous good health, who presented with right renal colic of one week duration. The imaging done at an outside hospital reported a right renal calculus and left ureterocele and was being managed conservatively with antibiotics and antispasmodics. He was referred to this center for urological evaluation. After two days of hospitalization at this center, he developed fever, touching to a maximum of 102°F which settled to 99°F the next day. All hematological and biochemical investigations [Table 1] carried out on two separate occasions were normal. Tests for hemoparasites and serological tests for typhoid and human immune deficiency virus (HIV) were negative. Urine was positive for albumin (++) with numerous pus cells on microscopic examination. Cultures from urine and blood were sterile.
Four days later, while remaining asymptomatic, he complained of pain right hypochondrium on deep breathing and had a bout of hemoptysis. On examination, he was febrile and had tachycardia (Pulse- 104/min) and tachypnoea (Resp- 34/min). Clinically, he had crepts in both lower lobes and right middle lobe with decreased breath sounds. There was tenderness in right hypochondrium and epigastrium. The antibiotic protocol was changed to parenteral broad spectrum antibiotics with supportive treatment. Subsequently, he had tonic clonic seizure that was managed with antiepileptics. Fundoscopy was normal. Total leukocyte count at this time was 2300/cumm with differential of 13% polymorphonuclear leukocytes and 82% lymphocytes associated with platelet counts of 80,000/cumm [Table1]. Gram stain of tracheal aspirate showed numerous gram positive cocci in clusters suggestive of Staphylococcus aureus [Figure 1] and the same was informed to the clinician and antibiotics changed in view of this finding. Due to continued low oxygen saturation, he was placed on ventillatory support, despite which his condition remained unresponsive and developed hypotension that was not controlled with inotrope support and ended fatally despite advanced cardiac life support. The clinical cause of death offered was of ARDS with bilateral pneumonitis.
The salient gross findings on post-mortem were of bilateral transudative pleural effusion, bilateral enlarged, voluminous and subcrepitant lungs with marked congestion specifically involving both lower lobes and right middle lobe [Figure 2]a and b. In addition, multiple mesenteric and paratracheal lymphnodes, 0.5 to 1.0 cm diameter were found and a small calculus was seen in lower third of right ureter. Cultures from heart blood taken post mortem and ante mortem tracheal aspirate grew methicillin resistant Staphylococcus aureus. Histopathological examination of lungs from congested areas showed extensive alveolar and interstitial hemorrhage and a moderate infiltrate of lymphocytes with a distinct paucity of neutrophils and numerous bacterial colonies with morphology of cocci in clusters [Figure 3]a. Gram stain showed numerous gram positive cocci in clusters [Figure 3]b. No vasculitis was seen. Multiple non-caseating discrete epithelioid cell granulomas with langhans type giant cells were seen to involve all lung lobes [Figure 4]a, liver [Figure 4]b and the lymph nodes [Figure 4]c. Some of the granulomas showed central necrosis. Extracellular eosinophilic PAS positive material was seen in the lymphnodes [Figure 4]d. PAS [Figure 5]a, Grocott [Figure 5]b and ZN stains [Figure 5]c for fungus and AFB carried out on sections of lungs, liver and lymphnodes were negative. Tissue polymerase chain reaction (PCR) for Mycobacterium tuberculosis from lungs and lymph nodes was negative. The cause of death was due to rapidly fatal hemorrhagic bilateral pneumonia due to MRSA in a case of sarcoidosis with consequent suppressed immunity.
| Discussion|| |
With emerging newer strains of organisms, hospital acquired pneumonias continue to be a major health problem. The different types of pneumonia syndrome are community acquired acute pneumonia, community acquired atypical pneumonia, nosocomial pneumonia, aspiration pneumonia, chronic pneumonia, necrotizing pneumonia and lung abscess, pneumonia in the immunocompromised.  S. pneumoniae accounts for 20-60% of cases of community acquired pneumonia (CAP) with H. influenzae contributing to 7-11% of cases. The other causative organisms include gram negative bacilli, group A and B Streptococci, M. cattarhalis, Legionella and viral pneumonias due to respiratory syncytial virus, influenza and parainfluenza viruses. S. aureus has been reported as the causative pathogen in 25.5% of CAP cases.  It can cause rapidly deteriorating necrotizing pneumonia as was seen in this case.
Enterobacteriacea and Pseudomonas account for majority of the nosocomial pneumonias with Staphylococcus aureus usually penicillin resistant contributing to a small percentage. S. aureus is the causative agent in approximately 30-50% of all HAP, ventilator-associated pneumonia (VAP), and health care-associated pneumonia (HCAP) cases. ,
Methicillin-resistant necrotizing pneumonia has recently been described as a novel clinical entity occurring predominantly in young immunocompetent patients. , It has been shown to be associated with leukopenia, hemoptysis, and extensive necrosis of the respiratory epithelium of the bronchi and the alveolar septa of the lung parenchyma.  These cases were found to be always associated with S. aureus strains producing an otherwise very infrequent exotoxin called Panton-Valentine leukocidin (PVL).  Pneumonia in cases of MRSA that produce PVL exotoxin are associated with leukopenia and will show a paucity of neutrophils in lung tissue despite the fact that it is a suppurrative infection.  The PVL strain cannot be treated by standard regimens.  β-lactam antibiotics, including penicillins and cefalosporins, may in fact, on the contrary, increase toxin formation. The British Society of Antimicrobial Therapy currently recommends linezolid and clindamycin, when the PVL strain is suspected as the cause of pneumonia. Rifampicin may have synergistic effects with linezolid and is recommended to be included in the management protocol of such cases. The PVL strain poses an increasing public-health problem and guidelines for community-acquired pneumonia may need to be revised.
Originally limited to the hospital setting, MRSA is a growing cause of infections in the community.  The definitions of HA-MRSA and CA-MRSA are also changing, and many different definitions can be found in the literature. They are defined by either the epidemiological setting where the infection occurs or by the molecular background of the infecting strains. There appears to be a merging of strains, which makes the definition and distinction even more challenging.
The causes of multisystem granulomatous lesions in such a setting would include tuberculosis, sarcoidosis and necrotising sarcoid granuolmas, fungi, foreign material, beryllosis, wegeners granulomatosis. Sarcoidosis is a multisystem granulomatous disease of uncertain origin. The peak incidence is between 20 to 39 yrs of age and has a female predeliction. The highest annual incidence has been reported between 5-40 cases/100,000 in northern European countries. It is associated with depressed cellular immunity with hypergammaglobulinemia and clinical energy with poor response to antigens like tuberculin.  Occurrence of suppressed cellular immunity and opportunistic infections as also tuberculosis, fungal infections, malignancies and autoimmune disorders has been described with sarcoidosis. 
The occurrence of suppurative pneumonia due to MRSA in a previously healthy individual with no known co-morbidities could possibly reflect an opportunistic infection in a setting of deranged cellular immunity in sarcoidosis in view of associated neutropenia associated with PVL exotoxin producing strains of S. Aureus.  Hypercalciuria occurs in 40% of patients with sarcoidosis, hypercalcemia in 11%, and renal calculi in 10%. Therefore, 24-hour urinary excretion of calcium should be measured in all patients with sarcoidosis. The case reported here presented with renal calculus. Though not a known recurrent stone former and serum and urinary calcium was not done in the case, the occurrence of renal calculus may be indirect evidence towards sarcoidosis. Moreover, sarcoidosis is a diagnosis of exclusion. Necrotizing sarcoid granulomas have not been reported in extra-pulmonary locations.
Disseminated tuberculosis accounts for 0.6% of all new cases. Mean duration of illness prior to diagnosis is 9.8 months. It can present with non-specific constitutional symptoms and hence a high degree of suspicion is required to establish the diagnosis.
Fungal pathology was excluded by special stains. There was no history to suggest consideration of foreign material or berryliosis in the differential diagnosis. Wegeners granulomatosis was excluded as there were no features of vasculitis in lungs or the kidneys.
A negative tissue PCR establishes the underlying cause as sarcoidosis with multisystem organ involvement in this case. Superimposed was nosocomial pneumonia due to methicillin-resistant pneumonia which caused a rapidly fatal hemorrhagic pneumonia in this case. Through the review of literature no case report of co-occurrence of sarcoidosis and staphylococcal pneumonia has been found.
| Conclusion|| |
The case report highlights the emergence of virulent strains of MRSA both in community and hospital settings that the medical fraternity needs to suspect in certain settings. PVL producing MRSA strains are associated with higher mortality and occurrence in immunocompetent individuals. The guidelines for antimicrobial therapy in suspected cases of MRSA pneumonia need to be revised with linezolid as the drug of choice. The occurrence of opportunistic infections has been reported earlier in sarcoidosis.  The association of sarcoidosis as an underlying cause of immuno-deficiency which could have aggravated the rapid progress of fatal outcome in such a case needs evaluation.
| Acknowledgment|| |
Department of Microbiology, AFMC, Pune for carrying out PCR
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Department of Pathology, MH Jalandhar
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]