Severe atypical pneumonia in critically ill patients: a retrospective multicenter study

We included 104 patients, 71 men and 33 women, with a median age of 56 [44–67] years (Additional file 2: Table S2). Acute respiratory failure was the main reason for ICU admission (n = 96; 92%); other reasons were cardiovascular failure (n = 2), neurological disorders (n = 3), and miscellaneous reasons (n = 3).

AP was more common in the fall and winter (Fig. 1). Furthermore, AP became more common over time, suggesting improved diagnosis after the introduction of PCR testing.

Table 1 and Additional file 3: Table S1 report the main features of the patients with AP. The most common comorbidity was chronic respiratory disease, which was present in 32 (31%) patients including 9 patients with chronic obstructive lung disease, 4 patients with asthma, and 4 patients with interstitial lung disease; of these 32 patients, 7 patients were on long-term oxygen therapy before ICU admission. Immunosuppression was noted in 21 patients including 10 (48%) with hematological malignancies (lymphoma, n = 6), 7 with solid cancer, and 2 with HIV infection. Delay from respiratory symptoms onset to ICU admission was 5 [3–8] days. A fever defined with a body temperature above 38.5 °C was present in 77 patients (74%). At ICU admission, all patients were tachypneic (respiratory rate, 32 [26–37]/min) and 48 (46%) had severe respiratory symptoms. Physical chest examination included crackles (n = 54; 52%), rhonchi (n = 15; 14%), wheezing (n = 12; 11%), and signs of consolidation (n = 7; 7%). No squeaks were reported. Extra-pulmonary symptoms concerned 34 (33%) patients and included arthritis (n = 2), myocarditis (n = 4), and skin rash (n = 6). Almost one-third of the patients (n = 32; 31%) had neurological symptoms at ICU admission, mostly with an altered level of consciousness related to severity of sepsis or to hypoxemia. Confusion was the main symptom for 3 (3%) patients, and meningo-encephalitis was diagnosed in 1 patient. Cold agglutinins assessed in case of hemolytic anemia were positive in 9 (9%) MP patients, cytolysis occurred in 11 (10%) patients, and rhabdomyolysis was present in 3 (3%) patients. At ICU admission, 10 (10%) patients had shock, the SOFA score was 5 [2–7], and the SAPS II was 33 [25–44].

The most common findings by chest radiography were alveolar opacities (n = 61, 59%), and interstitial opacities (n = 32, 31%) in 2 [1–4] quadrants. Pleural effusion was rare (n = 6, 6%).

The causative organism was MP in 76 (73%) patients and CP in 28 (27%) patients and was identified by serological testing (positive IgM or elevated IgG) in 71 patients, positive PCR on respiratory samples in 33 patients (18 on bronchoalveolar lavage, 10 on naso-pharyngeal aspirate, 2 on tracheal aspirate and 4 on nasal swab) and by both diagnostic methods in 5 patients. None of the collected variables differed between patients diagnosed with PCR, serology or both (Additional file 4: Table S3). Co-infection was found in 18 (20%) patients and was related to viruses (n = 9; influenza, rhinovirus, respiratory syncytial virus, coronavirus) or bacteria (n = 6; Haemophilus influenzae, Proteus mirabilis, Staphylococcus aureus, Serratia marcescens) or Pneumocystis jirovecii (n = 3). None of MP patients had co-infection with CP or SP.

Mechanical ventilation was required for 75 (72%) patients and lasted 13 [8–19] days. Of the 34 (45%) patients meeting criteria for ARDS, 4 required extracorporeal membrane oxygenation. Vasoactive agents were required for 41 (39%) patients, and renal replacement therapy was started for 10 (10%) patients.

The first-line antibiotics were active on MP and CP in 62 (60%) patients. Time from ICU admission to antibiotic initiation was 1 [0–4] day. Combination therapy was used in 61 (59%) patients and consisted to a third-generation cephalosporin (C3G) and a macrolide in 24 (39%) patients, a C3G and a quinolone in 13 (21%) patients, another betalactam and a macrolide in 16 (26%) patients, another betalactam and a quinolone in 6 (9%) patients, or another antibiotic and a macrolide in 2 (3%) patients. Antibiotics was adapted according to microbiology results with a macrolide (n = 72), a quinolone (n = 24) or a cycline (n = 3).

Eleven (11%) patients died in the ICU. ICU stay length was 16.5 [9.5–30.5] days. Persistent hypoxemia was present at ICU discharge in 60 (58%) patients. By univariate analysis, factors associated with mortality were age ≥ 65 years (p = 0.033), signs of respiratory distress (p = 0.017), and interstitial opacities on the chest radiograph (p = 0.017). For MP patients, 26 (34%) did not receive adequate antibiotic at ICU admission. Among them 2 patients died.

Tables 2 and 3 reports univariate analysis comparing patients with MP-AP and SP-P. Factors significantly associated with SP-P were HIV infection [12 (16%) vs. 2 (3%), p = 0.009], neurological symptoms [20 (26%) vs. 1 (1%), p < 0.0001], and gastrointestinal symptoms [15 (20%) vs. 1 (1%), p = 0.0003]. Factors significantly associated with MP were hemolytic anemia or cold agglutinins [0 (0%) vs. 9 (12%), p = 0.003]. Also, 6 patients with SP-P had co-infection (influenza A, n = 3; Haemophilus influenzae, n = 2; Streptococcus constellatus, n = 1).

SP-P was associated with a shorter length of respiratory symptoms before ICU admission (3 days [2–7] vs. 6 days [4–9], p = 0.0008). At ICU admission SAPS II score was higher for SP-P (42 [30–55] vs. 32 [22–41], p = 0.005), shock was more frequent (32% vs. 8%; p = 0.0004), creatinine level was higher (101 [69.5–168.8] μmol/L vs. 77 [57.5–108] μmol/L, p = 0.008), and lactate level was high (2.3 [1.8–3.4] mmol/l vs. 1 [0.07–2.7] mmol/l; p = 0.003).

Signs of consolidation and decreased breath sounds were more common in SP-P than in MP-AP (30% vs. 9% and 38% vs. 17%, respectively). MP-AP involved 4 quadrants on chest X-ray (26% vs. 8%, p = 0.013) but less frequently pleural space (5% vs. 11%, p = 0.007). The bilirubin level was higher in the patients with SP-P (15 [9.2–24.5] μmol/L vs. 8.4 [5.8–13] µmol/L, p = 0.0006). MP-AP was associated with the use of mechanical ventilation (66% vs. 50%, p = 0.049). ICU length of stay (LOS) seemed prolonged in case of MP-AP regardless of the ICU outcome (median LOS 37 vs. 5 days and 15 vs. 5 days, respectively, in patients who died in the ICU and in patients who were discharged alive). However, 28-day mortality was lower in the MP-AP group (5% vs. 20%, p = 0.005).

Figure 2 shows the MCA results for the clinical and radiological characteristics at admission. Several characteristics discriminated between MP and CP. MP was more often associated with hemolytic anemia, abdominal manifestations and extensive chest radiograph abnormalities. SP-P was associated with shock, confusion, focal crackles, and focal consolidation.