Respiratory syncytial virus pneumonia complicated by Streptococcus pneumoniae co-infection: two case reports and an analysis of their opposite outcomes

Introduction

Respiratory syncytial virus (RSV) can cause severe respiratory infections in elderly patients (1). Bacterial co-infections with Streptococcus pneumoniae (pneumococcus) are perilous (2) due to enhanced virulence when interacting with RSV-infected respiratory epithelium. Impaired mucociliary clearance in the airways promotes subsequent pneumococcal invasiveness (3,4).

We present case studies of a married couple both diagnosed with RSV pneumonia complicated by Streptococcus pneumoniae co-infection and bacteremia. Even though the same virus and the same bacterium were causing the pneumonia and despite similar health conditions, the outcomes were different. To explain this discrepancy, this paper describes the clinical courses and discusses risk factors for adverse outcomes. Established intensive care unit (ICU) scoring methods that are essential for outcome prediction and consequently the appropriate allocation of resources are queried. Moreover, the importance of the timely vaccination against invasive pneumococcal and RSV diseases in the elderly is promoted given the potentially lethal course of disease. We present this article in accordance with the CARE reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-23-139/rc).

Case presentation

The baseline characteristics of both patients are presented in Table 1 and the hospital course and respective outcomes are documented in Table 2. Computed tomography (CT) scans are shown in Figure 1 and the time course of the C-reactive protein (CRP) during hospitalization of both patients, as well as the creatinine concentration of patient 2 are provided in Figure 2. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). The wife (patient 1) gave written informed consent for herself and as a surrogate for her deceased husband (patient 2) for publication of this case report and accompanying figures. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 CT scans of the chest showing pulmonary infiltrates upon hospital admission of patient 1 (wife, A,B) and of patient 2 (husband, C,D), consistent with bilateral pneumonia. In addition, patient 2 had enlarged lymph nodes (arrowhead) and pulmonary nodules (arrows). CT, computed tomography.

Figure 2 Time course of CRP during hospitalization of patient 1 (orange, wife) and patient 2 (blue, husband). In addition, the creatinine concentration of patient 2 is depicted (dashed blue line). The kidney function of patient 1 remained normal (data not shown). A treatment timeline is provided below the x-axis. Patient 1 was treated intravenously with 1.2 g amoxicillin/clavulanic acid every 8 hours until day 8 (day of discharge), followed by 625 mg orally every 8 hours for two additional days. Patient 2 was treated initially with amoxicillin/clavulanic acid 1.2 g every 12 hours. Antibiotic therapy was escalated to piperacillin/tazobactam 4 g/0.5 g intravenously every eight hours on day 5 for another 14 days. CRP, C-reactive protein; VAP, ventilator-associated pneumonia; HDF, continuous veno-venous hemodiafiltration.

Patient 1

An 80-year-old woman with unremarkable past medical history presented to our emergency department on December, 2022, with productive cough, fever, shortness of breath and pleuritic chest pain starting ten days prior. She was a former cigarette smoker (15 pack-years). Upon admission, the patient was fully oriented, her blood pressure was 126/71 mmHg, the pulse rate was 116 beats/min, the respiratory rate was 21/min, the oxygen saturation was 89% while breathing ambient air. Auscultation revealed rales over both lungs. Laboratory tests showed elevated inflammatory parameters (Table 1). The PaO₂ was 10.2 kPa and the PaCO₂ was 3.89 kPa, consistent with hypoxemic respiratory insufficiency. Bibasilar pneumonic infiltrates were documented by CT scan (Figure 1A,1B). Evidence of RSV infection by nasal swab and growth of S. pneumoniae in blood cultures confirmed the diagnosis of a pneumonia caused by mixed infection with RSV and S. pneumoniae. The patient had not received prior pneumococcal vaccination. Antibiotic treatment with amoxicillin/clavulanic acid was established for 10 days; 1.2 g intravenously every eight hours for 8 days, and 625 mg every eight hours for the last two days. The patient got better and the CRP decreased promptly (Figure 2). She was discharged on day 8 with no medication other than the antibiotic and fully recovered over the next month.

Patient 2

The second patient, married to patient 1 and living in the same household, was an 80-year-old man with inconspicuous past medical history. He too was a former cigarette smoker (15 pack-years). The patient was admitted on the same day as his wife because of productive cough, progressive dyspnea and pleuritic chest pain in the past three days. On admission, the patient was fully oriented, his blood pressure was 138/77 mmHg, the pulse rate was 110 beats/min, the respiratory rate was 40/min and the oxygen saturation was 79% while breathing ambient air. Auscultation revealed rales over both lungs. Laboratory tests showed an elevated CRP concentration of 375 mg/L (normal <5 mg/L) and a leukopenia of 2.9 G/L (reference range 4.0–9.8 G/L), as well as elevated creatinine (209 µmol/L; reference range 62–110 µmol/L) and lactate concentrations (4.7 mmol/L; reference range 0.5–1.6 mmol/L). Prior laboratory data did not show a leukopenia. Therefore, this new finding was interpreted as a result of sepsis. Moreover, there was a hypo-osmolar hyponatremia (131 mmol/L; reference range 136–145 mmol/L). The PaO₂ was 6.9 kPa and the PaCO₂ was 3.54 kPa, consistent with hypoxemic respiratory insufficiency. Bilateral pneumonic infiltrates were detected by a CT scan (Figure 1C,1D). The pneumonia was caused by co-infection with RSV and S. pneumoniae: The RSV infection was documented by a positive nasal swab, and S. pneumoniae grew in blood cultures. Additionally, bi-pulmonary nodules and enlarged lymph nodes were noted in the CT scan, consistent with a reactive process in the context of the pneumonia (Figure 1C,1D). Since no malignant cells were found by bronchoalveolar lavage, the presence of a bronchial carcinoma was considered unlikely, however not impossible. Antibiotic treatment with amoxicillin/clavulanic acid 1.2 g every 12 hours was started (dose adjusted to the impaired renal function). The patient was transferred to the ICU. He had not received prior pneumococcal vaccination either.

The patient had to be intubated and mechanically ventilated and required vasopressor support. Increased purulent tracheal secretions, the decrease of the PaO₂/FiO₂ ratio from 179 to 140 mmHg, as well as rises in the leukocyte count from 15.9 to 20.9×10⁹/L and CRP value from 152 to 285 mg/L led to the diagnosis of ventilator-associated pneumonia on ICU day 5. However, no pathogen was isolated upon sampling of the tracheal secretions. The extensive bilateral pulmonary infiltrates were confirmed by chest X-ray. No other focus of infection was established and antibiotic therapy was empirically escalated to intravenous piperacillin/tazobactam 4 g/0.5 g every eight hours for 14 days.

Because of critical-illness polyneuro- and myopathy, tracheotomy was performed on ICU day 9. Continuous veno-venous hemofiltration was necessary because of increasing renal failure (Figure 2). Unfortunately, there was no organ function recovery. According to the patient’s advance directive, therapy was changed to palliation on day 24 and the patient passed away. A postmortem examination was not performed.

Discussion

We report the course of disease of a man and woman of the same age, ethnic and social background, and past medical history, living in the same household as a married couple. They had opposite outcomes of an RSV pneumonia complicated by S. pneumoniae bacteremia.

Mixed viral and bacterial infections in severe community-acquired pneumonia were shown to be significantly associated with an increased risk of in-hospital mortality, S. pneumoniae being the most common bacterium isolated (5). In a hospital-based cohort of adults with S. pneumoniae bacteremia, male sex and sepsis severity were among the factors associated with higher mortality rate (6). Angstwurm et al. found nonsurvival to be associated with significantly elevated 17beta-estradiol levels, with elevated progesterone in men and elevated testosterone in women (7), indicating the importance of sex hormones on the outcome of severe infections. Over the past years, evidence of sexual dimorphism in infectious disease susceptibility has accumulated. Men generate higher pro-inflammatory and potentially damaging cytokine levels [i.e., tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)] compared to women. Increased production of the anti-inflammatory IL-10 downregulates cytokine production by activated macrophages and T-helper cells in women (6,8-11).

Furthermore, if patient 2 had a previously un-diagnosed bronchial carcinoma, the concept of frailty as a surrogate of decreased physiological reserve when facing a critical illness such as sepsis (12) might be associated with the patient’s adverse outcome. In a systematic literature review, Puxty et al. reported that the average hospital mortality in cancer patients admitted to the ICU varied by tumor types, ranging from 4.6% to 76.8%. The factors associated with higher mortality were a poorer physiological score and functional status, as well as the need for invasive mechanical ventilation, especially when admitted to a medical ICU (13).

The baseline creatinine concentration of patient 2 was unknown. Therefore, it remains unclear whether the renal insufficiency was pre-existing. Nevertheless, the acute kidney injury (AKI) with oliguria was considered a complication of sepsis. Bagshaw et al. showed that septic AKI was a marker of illness severity, and was associated with higher need for mechanical ventilation and higher in-hospital mortality compared to nonseptic AKI (14).

In ICU patients, scoring methods such as Sequential Organ Failure Assessment (SOFA) (15), Acute Physiology and Chronic Health Evaluation (APACHE) II (16), and Simplified Acute Physiology Score (SAPS) II (17) are used to predict mortality (18). According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) in 2016, sepsis was defined as an acute change in SOFA score ≥2 points plus the evidence of an infection (19,20). APACHE II (16) is a simplified modification and revision of the original APACHE model, and is still considered the most common ICU mortality prediction score in the United States. SAPS II is an alternative to the APACHE II scoring system and is widely used in Europe. The SAPS II score shows a sigmoidal relationship with the in-hospital mortality rate (17).

Numerous comparative studies showed APACHE II and SAPS II to be equally reliable in quantifying the risk of death upon ICU admission (21-23). However, when comparing SOFA vs. APACHE II and SAPS II scores, the latter proved to be superior (22). Furthermore, according to Morkar et al. the best mortality prediction was obtained with a combination of SOFA plus SAPS II scores measured at 48 hours (24).

In the present case study, the survivor (patient 1) had SOFA, APACHE II and SAPS II scores predicting a mortality risk of 0%, 15% and 10.6%. The non-survivor (patient 2) had SOFA, APACHE II and SAPS II scores predicting a mortality risk of 50%, 55% and 75.3%, respectively. Therefore, the degree of organ dysfunctions measured at ICU admission and during the first 24 hours (or longer regarding the SOFA score) using established ICU scoring systems, correlates with the risk of adverse clinical outcomes. A limitation to our case report is that we do not have data available of hormone and cytokine levels, nor was a post-mortem examination performed on patient 2.

Regarding pneumococcal vaccine, prior immunisation has shown to improve survival and decrease the risk of respiratory failure and other complications amongst patients hospitalised with pneumonia (25). Therefore, major public health institutes recommend the vaccination of pneumococci for all adults over the age of 60 years. In the future, RSV infections of the respiratory tract in the elderly may be averted by a vaccination, which showed an efficacy of 65–85% in a recently published interim analysis of a phase III trial (26). By the same token, mixed RSV and S. pneumoniae infections may thus be prevented.

Conclusions

Despite the same age, health condition, social background, underlying infections and inflammatory response, the couple had opposite clinical outcomes. The number and degree of organ dysfunctions as measured by commonly used ICU scoring systems including the acute kidney injury, male sex, perhaps hormone levels, and nosocomial pneumonia have contributed to and prognosticated the husband’s death. High-risk patients need timely organ support in the ICU. However, their prognosis is dismal, which may limit resource allocation, especially in case of pertinent advance directives. Timely vaccination is highly recommended in order to prevent invasive pneumococcal disease. In addition, RSV infections of the respiratory tract may in the future be averted by the newly developed vaccination and should also be promoted in the elderly.

Acknowledgments

The authors would like to thank Dr. Ni Jian-Lüssi, MD for providing the CT scans depicted in Figure 1.

The abstract of this case report has been accepted as a poster presentation by the Swiss Society of Intensive Care Medicine (SSICM) for its annual congress in St. Gallen, Switzerland in September 2023.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-23-139/rc

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-23-139/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-23-139/coif). A.R. has received lecture fees from Labatec (Switzerland) and support for attending meetings from OrPha Swiss GmbH (Switzerland). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). The wife (patient 1) gave written informed consent for herself and as a surrogate for her deceased husband (patient 2) for publication of this case report and accompanying figures. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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