A rapidly deteriorating pneumonia: when the clinical course does not fit

Shareable abstract

Not all severe CAP is the same. Haemoptysis, cavitation and rapid deterioration should raise suspicion for Panton–Valentine leukocidin-driven disease. Early toxin-targeted therapy and recognition of mixed septic–cardiogenic shock may be key to survival. https://bit.ly/49KWALg

A 43-year-old woman, an ex-smoker (20 pack-years), presented with a 12-h history of fever, haemoptysis and rapidly progressive dyspnoea. She had a history of lung adenocarcinoma treated with left upper lobectomy and adjuvant chemotherapy 2 years earlier, with no evidence of recurrence on recent imaging. On arrival, she was in marked respiratory distress, with a respiratory rate of 35 breaths·min⁻¹, use of accessory respiratory muscles, and inability to complete a sentence. Arterial blood gas analysis on room air demonstrated hypoxaemic respiratory failure with metabolic acidosis (arterial oxygen tension (P_aO2) 42 mmHg, arterial carbon dioxide tension (P_aCO2) 26 mmHg, pH 7.33, lactate 1.9 mmol·L⁻¹). Laboratory investigations revealed a white blood cell count of 3900 cells·μL⁻¹ (normal range 4500–11 000 cells·μL⁻¹) and a C-reactive protein level of 36 mg·dL⁻¹ (normal range <0.9 mg·dL⁻¹); the remaining parameters were unremarkable. Chest computed tomography (CT) demonstrated extensive cavitary consolidation in the left lung with additional ground-glass opacities in the right lung (figure 1). Blood cultures and other microbiological samples were obtained, and empirical broad-spectrum antimicrobial therapy was initiated. Within 2 h in the emergency department, her respiratory status deteriorated further (P_aO2 75 mmHg, P_aCO2 52 mmHg, pH 7.22 on a non-rebreather mask, lactate 2.1 mmol·L⁻¹), prompting admission to the intensive care unit (ICU).

FIGURE 1.

Chest computed tomography performed in the emergency department, 12 h after symptom onset, revealed extensive necrotising consolidation with multiple cavitary lucencies involving the lingular segments of the left upper lobe and the superior segment of the left lower lobe. Additional patchy ground-glass opacities were noted in the right lung.

Task 1

Based on the clinical presentation and imaging findings, what is the most likely underlying process?

1. Acute pulmonary embolism with haemorrhagic infarction

2. Recurrence of lung adenocarcinoma with metastatic disease

3. Severe community-acquired pneumonia (CAP) with cavitary involvement

4. Diffuse alveolar haemorrhage due to vasculitis

5. Invasive pulmonary aspergillosis

Answer 1

c. The most likely underlying process is an acute infectious disease, particularly severe CAP. The hyperacute onset, including fever, haemoptysis and rapidly progressive respiratory failure, together with newly developed cavitary and infiltrative lesions, strongly supports an aggressive infectious aetiology.

Upon ICU admission, she was commenced on high-flow nasal cannula oxygen therapy. Transthoracic echocardiography revealed mild left ventricular systolic dysfunction (supplementary video 1), with an estimated ejection fraction of 45%, a right ventricle of normal size and systolic function, and an ultrasound-estimated cardiac output of 4.9 L·min⁻¹ (normal range ∼4–6 L·min⁻¹) and cardiac index of 2.95 L·min⁻¹·m⁻² (normal range ∼2.5–4.0 L·min⁻¹·m⁻²). Central venous oxygen saturation (S_cvO2) was 69%, and systemic vascular resistance estimation was 1045 dyn·s·cm⁻⁵ (normal range ∼900–1200 dyn·s·cm⁻⁵) with systemic vascular resistance index of 1735 dyn·s·cm⁻⁵·m⁻² (normal range ∼1970–2390 dyn·s·cm⁻⁵·m⁻²). Bedside lung ultrasound performed at ICU admission demonstrated scattered B-lines without evidence of consolidation in the right hemithorax. At this stage, vasopressor support was not required, and empirical antimicrobial therapy was escalated to cover severe CAP requiring ICU-level care.

Shortly after ICU admission, the patient's respiratory status deteriorated further, and 4 h later endotracheal intubation was required due to worsening gas exchange (P_aO2 58 mmHg, P_aCO2 70 mmHg, pH 7.15, inspiratory oxygen fraction (F_IO2) 100% on high-flow oxygen). Repeat bedside lung ultrasound examination revealed marked interval change on lung ultrasound, with new extensive right lower lobe consolidation (figure 2 and supplementary video 2). Due to the patient's clinical instability, repeat CT imaging was not feasible.

FIGURE 2.

Lung ultrasound demonstrating extensive consolidation of the right lower lobe with a tissue-like (“hepatisation”) pattern, consistent with severe loss of aeration. The consolidated lung appears similar in echotexture to the adjacent liver due to alveolar filling with inflammatory exudate. The diaphragm is clearly visualised, separating the lung from the liver.

Along with the respiratory worsening, her haemodynamic status deteriorated significantly as well. Vasopressor support was initiated with noradrenaline, which required rapid escalation to 3.15 μg·kg⁻¹·min⁻¹ as haemodynamic deterioration progressed. Laboratory reassessment showed a rising lactate level of 6.5 mmol·L⁻¹, while S_cvO2 decreased to 56%. Estimated systemic vascular resistance was 966 dyn·s·cm⁻⁵. The combination of rising lactate, relatively low S_cvO2 and declining ultrasound-estimated cardiac output indicated worsening global tissue hypoperfusion despite escalating vasopressor support. Repeat transthoracic echocardiography was performed and it demonstrated a striking and rapid deterioration in global left ventricular systolic function (figure 3, supplementary videos 1 and 3). The ejection fraction declined from 45% at admission to ∼25% at 4 h and further to <15% at 6 h. The impairment was global, without segmental wall motion abnormalities. Ejection fraction is load dependent and may be influenced by rapid changes in preload and afterload during mechanical ventilation and vasopressor therapy; notably, the right ventricle remained normal in size and systolic function. ECG showed sinus tachycardia without ischaemic changes, and this pattern remained unchanged throughout the patient's course. Troponin T was elevated at 0.57 ng·mL⁻¹ (normal range <0.015 ng·mL⁻¹). Vasopressor requirements increased further, prompting the addition of vasopressin (0.03 units·min⁻¹) and hydrocortisone (200 mg·day⁻¹ as a continuous infusion). In the absence of haemodynamic improvement, noradrenaline was progressively titrated up to 6.4 μg·kg⁻¹·min⁻¹, with a mild further reduction in systemic vascular resistance despite escalating doses.

FIGURE 3.

Serial transthoracic echocardiography demonstrating rapid deterioration in left ventricular function over a short time interval. a) On admission to the intensive care unit, left ventricular systolic function was mildly reduced (ejection fraction ∼45%), with a left ventricular end-diastolic diameter (LVEDD) of 42 mm (normal range in women ∼38–52 mm). b) Following intubation, systolic function deteriorated markedly (ejection fraction ∼25%), with an increase in LVEDD to 51 mm. c) At a later stage of ongoing haemodynamic deterioration, systolic function further declined (ejection fraction <15%), with LVEDD increasing to 60 mm.

Task 2

What is the most likely mechanism of shock in this patient?

1. Pure distributive (septic) shock

2. Obstructive shock due to massive pulmonary embolism

3. Mixed distributive and cardiogenic shock

4. Hypovolaemic shock due to haemoptysis

5. Acute myocardial infarction with cardiogenic shock

Answer 2

c. The most likely mechanism is rapidly progressive mixed distributive and cardiogenic shock in the context of severe infection. The rapid global deterioration in left ventricular systolic function, rising lactate levels and escalating vasopressor requirements are consistent with a mixed septic–cardiogenic shock state with significant myocardial involvement. S_cvO2 was reduced but not as low as might be expected for the degree of cardiogenic shock, consistent with impaired oxygen extraction and utilisation in the setting of sepsis. The absence of regional wall motion abnormalities and ischaemic ECG changes makes acute myocardial infarction unlikely, particularly in a relatively young patient.

Task 3

1) What is the most likely unifying diagnosis explaining this clinical course?

• a) Severe necrotising pneumonia complicated by acute myocardial infarction with cardiogenic shock

• b) Acute pulmonary embolism complicating severe pneumonia with haemodynamic collapse

• c) Viral myocarditis with secondary pneumonia

• d) Fulminant necrotising pneumonia complicated by sepsis-induced cardiomyopathy

2) What is the most appropriate treatment strategy for this patient at this stage?

• a) Treatment for presumed fulminant myocarditis

• b) Immediate thrombolysis for suspected massive pulmonary embolism

• c) Urgent coronary angiography and revascularisation for presumed acute myocardial infarction

• d) Immediate broad-spectrum antimicrobial therapy and aggressive haemodynamic support for mixed septic–cardiogenic shock

• e) Conservative treatment with oxygen supplementation and diuretics

Answer 3

1) d. The most likely diagnosis is fulminant necrotising pneumonia complicated by sepsis-induced cardiomyopathy and mixed septic–cardiogenic shock. The hyperacute clinical course, cavitary lung destruction and global myocardial dysfunction without ischaemic features, together with the absence of an appropriate increase in systemic vascular resistance, support a mixed shock state with both cardiogenic and distributive components. The absence of regional wall motion abnormalities, right ventricular dysfunction or a preceding viral syndrome, together with the lack of ECG evidence of myocardial ischaemia despite troponin elevation, made acute myocardial infarction, pulmonary embolism and viral myocarditis less likely.

2) d. The most appropriate strategy is immediate broad-spectrum antimicrobial therapy and aggressive haemodynamic support for mixed septic–cardiogenic shock. Management requires prompt ICU-level resuscitation, including early broad-spectrum antibiotics with consideration of toxin-suppressive agents (e.g. linezolid or clindamycin), lung-protective ventilation and vasopressor support. In the presence of persistent hypoperfusion and cardiac dysfunction, the addition of an inotropic agent should be considered.

Despite escalation of supportive therapy, including addition of dobutamine as an inotropic agent and initiation of levosimendan, the patient showed no haemodynamic improvement (figure 3c, supplementary video 4). Ultrasound-estimated cardiac output decreased to 2.9 L·min⁻¹ and heart rate increased to 141 beats·min⁻¹. Haemodynamic parameters suggested fluid unresponsiveness, with central venous pressure >10 mmHg and pulse pressure variation <8%.

Mechanical ventilation maintained acceptable oxygenation with a tidal volume of 380 mL, positive end-expiratory pressure of 10 cmH₂O, F_IO2 90% and plateau pressure 27 cmH₂O. Arterial blood gas analysis showed P_aO2 75 mmHg, P_aCO2 47 mmHg and persistent metabolic acidosis (pH 7.13, lactate 8.2 mmol·L⁻¹). These findings suggested that respiratory failure alone did not fully account for the clinical deterioration.

Given the rapidly progressive refractory shock due to severe left ventricular dysfunction, veno-arterial extracorporeal membrane oxygenation or mechanical circulatory support with an Impella device were considered. However, neither modality was available at our institution, and transfer to a specialised centre was not feasible due to extreme haemodynamic instability. Despite maximal supportive measures, the patient died 20 h after ICU admission due to refractory cardiogenic shock.

From the tracheobronchial aspirate culture, a pathogen was identified. Blood cultures were negative. Empirical broad-spectrum antimicrobial therapy had been initiated immediately upon presentation and included linezolid for toxin-suppressive coverage, given the presence of cavitary lesions and the fulminant clinical presentation.

Task 4

Which pathogen is most likely to be responsible for this clinical syndrome?

1. Streptococcus pneumoniae

2. Staphylococcus aureus

3. Pseudomonas aeruginosa

4. Klebsiella pneumoniae

5. Trypanosoma cruzi

Answer 4

b. The most likely causative organism is Panton–Valentine leukocidin (PVL)-producing S. aureus. This pathogen is associated with fulminant necrotising pneumonia characterised by haemoptysis, cavitation, leukopenia and rapid clinical deterioration. The diagnosis is supported by subsequent identification of a PVL-producing pathogen in tracheobronchial aspirate.

The final diagnosis for our patient was fulminant necrotising pneumonia due to PVL-producing methicillin-resistant S. aureus, complicated by rapidly progressive sepsis-induced cardiomyopathy and refractory mixed septic–cardiogenic shock.

Discussion

Severe CAP encompasses a wide clinical spectrum, ranging from self-limited infection to rapidly progressive disease requiring intensive care support. A subset of patients presents with fulminant deterioration characterised by early respiratory failure, haemodynamic instability and multi-organ dysfunction. Necrotising pneumonia represents one of the most severe forms within this spectrum and is associated with extensive parenchymal destruction, impaired pulmonary perfusion and high mortality rates approaching 40–50% in some series [1, 2]. Unlike uncomplicated CAP, the disease process in necrotising pneumonia extends beyond alveolar infection and involves vascular compromise, microthrombosis, tissue infarction, cavitation and reduced antibiotic penetration [2]. In the present case, the abrupt onset of haemoptysis, severe hypoxaemia, leukopenia, high inflammatory burden and early cavitating infiltrates pointed towards this aggressive phenotype from the first hours of presentation. This temporal pattern should alert clinicians to a destructive and systemic process rather than a localised pulmonary infection. Similar fulminant presentations have been described in PVL-associated necrotising pneumonia, often progressing rapidly to respiratory failure and shock, including in previously healthy individuals [3, 4].

Among the pathogens associated with necrotising pneumonia, S. aureus, particularly strains producing PVL, has been consistently linked to severe and often fatal disease. PVL is a bicomponent pore-forming cytotoxin that targets neutrophils, leading to leukocyte lysis, amplification of the inflammatory response and tissue necrosis [5, 6]. Although PVL is present in only a minority of S. aureus strains, infections caused by PVL-positive organisms are disproportionately associated with severe clinical manifestations, including necrotising pneumonia, sepsis and invasive disease [6, 7]. Large cohort data suggest that PVL positivity is independently associated with mortality in adults with severe staphylococcal CAP, irrespective of methicillin resistance or other virulence determinants [8]. In our patient, haemoptysis, leukopenia, rapidly progressive cavitary lung destruction and early haemodynamic compromise were consistent with this toxin-mediated phenotype. Similar patterns have been reported across case descriptions of PVL-associated pneumonia and fulminant staphylococcal infection [9, 10]. In some cases, this constellation has been conceptualised as a “PVL syndrome”, encompassing pneumonia, septic shock and systemic complications [11]. This concept is useful clinically but should not be overinterpreted, as PVL is likely to be only one component of a multifactorial process.

Recognition of toxin-mediated infection has important therapeutic implications. Conventional antimicrobial strategies based solely on bacterial susceptibility may be insufficient, as clinical deterioration has been reported despite appropriate, organism-sensitive antibiotics [9–11]. This apparent paradox reflects the fact that bacterial killing does not immediately halt toxin production or reverse host-mediated tissue injury. For this reason, protein synthesis inhibitors, such as clindamycin or linezolid, have been advocated to suppress toxin production and limit disease progression [4, 11]. In the present case, empirical treatment was escalated early because the cavitary pattern and fulminant course raised concern for severe staphylococcal disease. Nevertheless, the patient continued to deteriorate, highlighting the difficulty of reversing toxin-mediated illness once systemic involvement has developed. In addition, the structural changes of necrotising pneumonia, including vascular compromise, thrombosis and parenchymal destruction, may impair antibiotic delivery to infected lung tissue [2].

Beyond pulmonary involvement, the most striking feature of this case was the abrupt transition from severe CAP to mixed septic–cardiogenic shock. On ICU admission, left ventricular systolic dysfunction was only mild. Within hours, serial echocardiography demonstrated rapidly progressive global left ventricular failure, accompanied by rising lactate, falling cardiac output, escalating vasopressor requirements and persistent metabolic acidosis. This pattern supports sepsis cardiomyopathy rather than a primary coronary or inflammatory myocardial disease [12, 13]. Acute myocardial infarction was unlikely because the dysfunction was global rather than regional, the ECG showed sinus tachycardia without ischaemic changes, and the clinical course occurred in parallel with overwhelming infection rather than a primary coronary syndrome. Myocarditis can also cause acute global systolic dysfunction, but in this patient, there was no preceding clinical syndrome suggesting myocarditis, and the timing of cardiac decline closely followed worsening septic physiology [14], and the haemodynamic profile, including the absence of an appropriate increase in systemic vascular resistance and only moderately reduced S_cvO2, was not consistent with isolated cardiogenic shock. The available data therefore support myocardial depression as part of sepsis-induced organ dysfunction rather than a separate myocardial diagnosis.

Sepsis-induced cardiomyopathy remains incompletely defined and is generally understood as acute myocardial dysfunction occurring during sepsis, not explained by ischaemia or pre-existing cardiac disease, and often involving systolic, diastolic or right ventricular impairment [12, 13]. Its reported prevalence varies widely, reflecting heterogeneous definitions and the difficulty of assessing cardiac performance under rapidly changing preload and afterload conditions [14]. In this context, left ventricular systolic dysfunction may represent a more readily interpretable marker of myocardial impairment, particularly in the setting of reduced systemic vascular resistance, whereas diastolic dysfunction may pre-exist and right ventricular function may be influenced by factors such as mechanical ventilation, pulmonary pathology and hypoxaemia [14]. Mechanistically, myocardial dysfunction in sepsis is not primarily driven by coronary hypoperfusion. Inflammatory mediators, nitric oxide dysregulation, mitochondrial dysfunction, oxidative stress, calcium-handling abnormalities and impaired cellular energetics all contribute to reduced contractility and impaired oxygen utilisation [12, 15]. The early and rapidly progressive nature of myocardial dysfunction in this case is notable and may represent an under-recognised manifestation of toxin-mediated disease, potentially contributing to adverse outcomes in otherwise healthy individuals.

In this context, the haemodynamic pattern observed in our patient was not explained by pure distributive shock. In isolated septic shock, cardiac output is greatly increased, whereas this patient developed a marked fall in systolic function and relative reduction in cardiac output. Conversely, in isolated cardiogenic shock, systemic vascular resistance would usually rise substantially as a compensatory response; in this case, systemic vascular resistance was not appropriately elevated despite high-dose noradrenaline, supporting a concomitant distributive component. Although very high-dose noradrenaline may increase ventricular afterload and contribute to impaired cardiac performance, systemic vascular resistance remained low (inappropriately normal) despite escalating doses, supporting persistent vasoplegia rather than isolated afterload-induced cardiac failure. The S_cvO2 was reduced, but not as low as might be expected for the degree of hypoperfusion, consistent with the recognised impairment of oxygen extraction and utilisation in sepsis. Similarly, ejection fraction is load dependent and may overestimate intrinsic contractility in septic shock. Integration of serial echocardiography with flow-related variables such as velocity–time integral and systemic vascular resistance can better characterise septic cardiomyopathy phenotypes [16].

The role of serial bedside imaging is therefore central to the interpretation of this case. A single echocardiogram at ICU admission could have underestimated the severity and speed of the cardiovascular transition, because the first investigation showed only mild systolic dysfunction and no need for vasopressors. The subsequent examinations, performed during clinical deterioration, revealed the trajectory: progressive left ventricular dilatation and collapse of systolic function over hours. This dynamic information changed the physiological interpretation of shock from severe pneumonia with vasoplegia to a mixed shock state in which myocardial failure became dominant. The lung ultrasound findings were similarly important. Initial right-sided examination showed scattered B-lines without consolidation, whereas repeat imaging demonstrated right lower lobe consolidation with loss of aeration. In a patient too unstable for repeat CT, the combination of serial lung ultrasound and echocardiography provided bedside evidence that both the pulmonary and circulatory processes were evolving rapidly [14, 17].

These distinctions matter therapeutically. Standard sepsis resuscitation remains essential, including early source-directed antimicrobials, vasopressor support and lung-protective ventilation, but recognition of a cardiogenic component should prompt repeated assessment of cardiac output and tissue perfusion rather than reflexive fluid escalation. In refractory vasodilatory shock, adjunctive vasopressors such as vasopressin are recommended to reduce escalating catecholamine exposure [18]; however, in the present case, the exceptionally rapid haemodynamic evolution led to initial noradrenaline escalation, while serial assessment revealed the emergence of a dominant cardiogenic component requiring inotropic support. In patients with persistent hypoperfusion and documented cardiac dysfunction, inotropic support may be considered, although evidence for any specific agent remains limited. Levosimendan has been explored in severe septic cardiomyopathy, but available data support only possible benefit in selected patients [19]. In the present case, the lack of haemodynamic response despite dobutamine and levosimendan, together with the rapidly worsening ventricular function, illustrates the limited therapeutic window once fulminant myocardial failure has developed. Advanced circulatory support may be considered in refractory cases, but evidence is limited and feasibility depends on institutional resources and safe transfer [20].

Taken together, this case illustrates how toxin-mediated infection can drive a rapidly evolving interplay between pulmonary destruction and cardiovascular failure, requiring continuous reassessment of both disease trajectory and underlying physiology.

Conclusion

This case highlights how rapidly progressive CAP can evolve into fulminant systemic illness when driven by toxin-mediated mechanisms. Necrotising pneumonia should be suspected early in patients with haemoptysis, leukopenia, cavitary infiltrates and deterioration disproportionate to initial findings. In this setting, S. aureus, especially PVL-producing strains, should be considered because of its association with aggressive disease and high mortality. Recognition of this phenotype is critical, as management may require early toxin-suppressive therapy, such as clindamycin or linezolid, alongside conventional antimicrobial coverage. Severe infection may also be complicated by early and rapidly progressive sepsis-induced cardiomyopathy and mixed septic–cardiogenic shock, requiring careful haemodynamic and echocardiographic interpretation. Ultimately, this case underscores the need for early suspicion, rapid escalation of antimicrobial and supportive therapies, and multidisciplinary management of hyperacute toxin-mediated respiratory infection.

Supplementary material

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Supplementary video 1 EDU-0120-2026.SUPPLEMENT ^{(489.9KB, mp4)}

Supplementary video legends EDU-0120-2026.SUPPLEMENT ^{(100.6KB, pdf)}

Supplementary video 2 EDU-0120-2026.SUPPLEMENT2 ^{(922.5KB, mp4)}

Supplementary video 3 EDU-0120-2026.SUPPLEMENT3 ^{(442.1KB, mp4)}

Supplementary video 4 EDU-0120-2026.SUPPLEMENT4 ^{(1MB, mp4)}