Introduction: Acute eosinophilic pneumonia (AEP) is a rare respiratory condition caused by eosinophil accumulation in the pulmonary tissue that can be related to drug administration. Daptomycin, an antibiotic active against gram-positive bacteria, is one of the leading causes of AEP among drugs. In order to raise awareness of this rare syndrome, in our work we have described a case of an 82-year-old male with Enterococcus faecalis endocarditis treated with daptomycin, who developed a daptomycin-induced AEP. We have performed a systematic review of the literature for all similar reported cases. Methods: The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To conduct the analysis, the terms “daptomycin AND eosinoph* AND pneum*” were entered into the databases Medline, CINAHL, and Embase on April 13, 2023. We considered all relevant records documenting AEP after daptomycin use. No restrictions in terms of year or language were made. A formal appraisal of observational studies was performed by Newcastle-Ottawa Scale. All results and data were reported by means of tables. Results: Our search identified 93 relevant records, published between 2007 and 2023. A total of 120 patients were considered. Patients who experienced AEP were mostly males (n = 88, 73.3%) with a mean age of 68.28 years (SD 11.54). Daptomycin was most frequently prescribed for osteoarticular infections (n = 75, 62.5%) and to treat gram-positive cocci infections. The most frequently isolated pathogen was methicillin-resistant Staphylococcus aureus. Daptomycin was mostly used with off-label indications (n = 89, 74%). Symptoms of AEP were usually reported after a mean of 21.75 days of treatment (range 3–84) and typically included fever, dyspnea, dry cough, and acute respiratory failure. Reported treatment strategies invariably included daptomycin withdrawal, respiratory support, and corticosteroid treatment. One hundred and sixteen patients fully recovered. A fatal outcome was described in 4 patients. Suggestive symptoms and imaging raised suspicion for AEP, confirmed with bronchoalveolar lavage in 57.5% of the cases. Discussion and Conclusions: Daptomycin-induced AEP is a rare but potentially fatal complication, mostly reported after long treatment with daptomycin. Clinicians should be aware of this syndrome, as it could be initially misdiagnosed for an acute infectious respiratory syndrome, resulting in a delay in its diagnosis and treatment. Furthermore, since the risk of developing AEP is increased by longer drug exposure, caution should be used when discussing the use of daptomycin in longer treatment regimens.

Acute eosinophilic pneumonia (AEP) is a rare respiratory syndrome caused by eosinophil accumulation in the pulmonary tissue, first reported in 1989 [1, 2]. It has been described as an acute febrile illness with respiratory failure and eosinophilic pulmonary infiltrates on lung biopsy or bronchoalveolar lavage (BAL), often associated with peripheral eosinophilia [3, 4]. During the course of the disease, various degrees of respiratory failure may ensue, requiring corticosteroid therapy and respiratory support up to invasive mechanical ventilation [5, 6]. Although the pathogenesis of AEP is not fully understood, several factors such as tobacco smoke, infections, several drugs such as non-steroidal anti-inflammatory drugs, anticonvulsants, antidepressants, antibiotics, and cardiovascular medications are reported among the most frequent causes [5, 7]. Among the antibiotics, daptomycin appears to be strongly correlated with drug-induced AEP. This antibiotic is a cyclic lipopeptide, with bactericidal activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus (VRE). Daptomycin was approved in 2003 by the Food and Drug Administration (FDA) for the treatment of complicated skin infections, bloodstream infections, and endocarditis, but several off-label uses have been reported, as treatment for diabetic foot infections [8] or osteomyelitis [9]. After the first case of daptomycin-induced AEP documented in 2007 [7], pulmonary eosinophilia was added to the “Adverse Reactions, Post-Marketing Experience” section of the drug [10]. Several mechanisms have been proposed to explain daptomycin-induced AEP, such as conformational changes of membrane ion channels allowing for altered ion exchange, a higher drug concentration on alveolar epithelium due to surfactant-binding, causing cellular injury, and an increased release of eotaxin and interleukin-5 induced by the drug, leading to an eosinophil migration to the lungs [4, 7, 11]. Daptomycin-induced AEP should be suspected after several days of drug exposure, in the presence of specific BAL/bioptic findings and if there is a rapid symptoms’ improvement after drug discontinuation. During the course of the disease, various degrees of respiratory failure may ensue, requiring corticosteroids and respiratory support up to invasive mechanical ventilation [5, 6].

For the definite diagnosis of AEP, two diagnostic classifications are in use, the FDA criteria, which categorize daptomycin-induced AEP as unlikely, possible, probable, and definite [10], and the criteria proposed by Solomon. and Schwarz in 2006 for AEP, including drug re-challenge among risk factors and, therefore, among diagnostic criteria [5]. Both diagnostic criteria are reported and compared in Table 1.

Table 1.

Diagnostic criteria for AEP

FDA criteria [10]Soloman and Schwarz [5]
DefiniteProbablePossibleUnlikely-
Concurrent exposure to daptomycin Concurrent exposure to daptomycin Concurrent exposure to daptomycin All other cases that did not meet criteria Presence of simple, acute, or chronic eosinophilic pneumonia by diagnostic criteria which includes excess of eosinophils on either lung biopsy or BAL (usually ≥25%) in the setting of parenchymal infiltrates 
Dyspnea with increased oxygen requirement or requiring mechanical ventilation Dyspnea with increased oxygen requirement or requiring mechanical ventilation New infiltrates on CXR or CT  Presence of a potential candidate drug or toxin in an appropriate time frame 
New infiltrates on CXR or CT New infiltrates on CXR or CT Clinical improvement following daptomycin withdrawal or the patient died  No other cause of eosinophilic pneumonia such as fungal or parasitic infections 
BAL with >25% eosinophils BAL with <25% eosinophils or peripheral eosinophilia   Clinical improvement after cessation of the drug or toxin 
Clinical improvement following daptomycin withdrawal Clinical improvement following daptomycin withdrawal   Recurrence of eosinophilic pneumonia with re-challenge to the drug or toxin 
Fever     
FDA criteria [10]Soloman and Schwarz [5]
DefiniteProbablePossibleUnlikely-
Concurrent exposure to daptomycin Concurrent exposure to daptomycin Concurrent exposure to daptomycin All other cases that did not meet criteria Presence of simple, acute, or chronic eosinophilic pneumonia by diagnostic criteria which includes excess of eosinophils on either lung biopsy or BAL (usually ≥25%) in the setting of parenchymal infiltrates 
Dyspnea with increased oxygen requirement or requiring mechanical ventilation Dyspnea with increased oxygen requirement or requiring mechanical ventilation New infiltrates on CXR or CT  Presence of a potential candidate drug or toxin in an appropriate time frame 
New infiltrates on CXR or CT New infiltrates on CXR or CT Clinical improvement following daptomycin withdrawal or the patient died  No other cause of eosinophilic pneumonia such as fungal or parasitic infections 
BAL with >25% eosinophils BAL with <25% eosinophils or peripheral eosinophilia   Clinical improvement after cessation of the drug or toxin 
Clinical improvement following daptomycin withdrawal Clinical improvement following daptomycin withdrawal   Recurrence of eosinophilic pneumonia with re-challenge to the drug or toxin 
Fever     

FDA, Food and Drug Administration; BAL, bronchoalveolar lavage; CXR, chest X-ray; CT, computed tomography.

We hereby present a case of an 82-year-old male with Enterococcus faecalis endocarditis complicated by rapid worsening of respiratory function after prolonged daptomycin exposure, with clinical features that appeared to endorse a daptomycin-induced AEP. In order to provide a better understanding of the topic and in the attempt of summarizing similar cases, a systematic review of the literature was also performed.

An 82-year-old man with hypertension, chronic kidney disease, coronary artery disease, aortic valve replacement (biologic), atrioventricular block treated with pacemaker insertion, paroxysmal atrial fibrillation, coxarthrosis subjected to hip arthroplasty, and no prior documented allergy was admitted to our emergency room complaining of high fever and confusion. He was recently hospitalized due to SARS-CoV2 pneumonia and had a concomitant vancomycin-susceptible E. faecalis bacteremia, treated with piperacillin/tazobactam and vancomycin for 10 days. Since being discharged, he experienced persistent low-grade fever, unresponsive to antibiotics.

After admission to our hospital, laboratory results showed neutrophilic leukocytosis (white blood cells 18,000/mm3, neutrophils 95%), increased pro-inflammatory markers (C reactive protein 22 mg/L [normal range 0.00–5.00 mg/L]), worsening of kidney function, and hyperkaliemia. In the suspicion of infective endocarditis, empirical antibiotic therapy with daptomycin and piperacillin/tazobactam was started. After 2 days, blood cultures requested before antibiotic start resulted positive for E. faecalis, and a transthoracic echocardiography showed aortic valve endocarditis on the non-coronary cusp and left coronary cusp (0.4 × 0.2 cm); hence, antibiotic treatment was switched to ampicillin 2 g every 4 h and plus ceftriaxone 2 g every 12 h. Given the evidence of concomitant infective involvement of the pacemaker leads documented on a PET-computed tomography (CT) scan, ceftriaxone was replaced with daptomycin (10 mg/kg), to improve biofilm penetration, as various studies report daptomycin as a choice for increased biofilm penetration [12, 13]. After 18 days of therapy with daptomycin, the patient presented new onset fever, cough, dyspnea, and radiological evidence of pneumonia, as shown in Figure 1, requiring oxygen supply. Because of the rapid worsening of the clinical conditions, an empiric therapy was started pending microbiological culture results. Due to the positivity of the surveillance rectal swabs for carbapenemase productive Klebsiella pneumoniae and the isolation of Klebsiella oxytoca from a sputum sample, ceftazidime-avibactam and intravenous fosfomycin were added to therapy, but no improvements were observed after 72 h. Liposomal amphotericin B was started, because of radiological findings suggestive of fungal pneumonia, with no clinical improvement. Laboratory tests showed increased white cell count (up to 13,190/mm3) associated with a significant increase of eosinophil percentage (11%) and inflammatory indicators (C reactive protein 510.6 mg/L). Blood cultures were persistently negative. A bronchoscopy was performed, and BAL fluid culture tested negative for bacteria, viruses, fungi, and parasites. After the negative culture results, antibiotic and antifungal empiric therapy was stopped. Daptomycin-induced AEP was then suspected: antibiotic treatment was switched to ampicillin-only regimen, and intravenous methylprednisolone was started. The patient rapidly improved after daptomycin suspension: supplemental oxygen was withdrawn, white cell count went back to normal, and inflammatory indicators decreased dramatically. Thirteen days after the suspension of daptomycin, the patient was discharged home, in good clinical conditions on oral therapy with amoxicillin/clavulanic acid. Two sets of blood cultures were performed on the 15th day after discharge, which resulted negative. After 12 months, the oral antibiotic suppressive therapy was suspended, after obtaining a PET-TC that showed no evidence of endocarditis.

Fig. 1.

Chest CT scan of the described case at 18 days of treatment with daptomycin.

Fig. 1.

Chest CT scan of the described case at 18 days of treatment with daptomycin.

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Systematic Review of the Literature

The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [14]. An initial search was performed on the computerized databases Medline, CINAHL and Embase, via an all-term search of the terms “daptomycin AND eosinoph* AND pneum*.” The exact search strategy is available in online supplementary Table S1 (for all online suppl. material, see https://doi.org/10.1159/000535190). The search included titles from inception to April 13, 2023. No restriction in terms of language or country was applied. Studies were considered eligible if they reported a description of clinical cases of onset of eosinophilic pneumonia after the administration of daptomycin without restriction to any particular bacterial infection. All study designs except reviews were considered eligible, including conference posters and abstracts. Records reporting only aggregated data of multiple patients were considered ineligible for inclusion.

A first pool of records was obtained by searching each indexed database. Obtained records were merged on the online resource Rayyan for de-duplication [15]. After the first round of screening by title and abstract, the remaining studies were examined for inclusion by reading their full text. Screening and selection of records was performed in blind by L.V.R. and A.D.L. Discrepancies in selection were solved by confrontation or by contacting the review leader, L.S.

Extracted data included article title, first author, year of publication, study design, age and gender of the discussed patient, type of infection requiring treatment with daptomycin, microbiological isolate, daptomycin posology and days of treatment before the onset eosinophilic pneumonia, data about the execution of BAL, degree of certainty of diagnosis according to the FDA criteria, outcome of eosinophilic pneumonia. All extracted data were entered in a computerized database and then summarized by means of tables in the present paper. A formal appraisal of observational studies was performed via Newcastle-Ottawa Scale (NOS) and is included in online supplementary material Table S2.

The initial search identified 274 records. After deduplication, 191 records were included by reading the title and abstract only. One hundred and two articles were deemed relevant and examined by reading the full text. A final pool of 93 articles was considered and therefore proceeded to the data extraction phase, including a total of 120 patients. Eligible studies included 6 case series, 34 case reports, 46 conference abstracts/posters, 5 editorials, and 2 cohort studies. Publication year ranged between 2007 and 2023. The selection process is depicted in Figure 2.

Fig. 2.

PRISMA flowchart of article selection process.

Fig. 2.

PRISMA flowchart of article selection process.

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Mean age of the reported cases was 68.28 years (SD ± 11.54), and the majority of patients were males (73.9%; n = 88). Daptomycin was most frequently prescribed for osteomyelitis, septic arthritis, or spondylodiscitis (n = 39), prosthetic joint infection (n = 36), SSTI/wound infection/diabetic foot ulcer (n = 22), bacteremia/sepsis (n = 23) or wound infection or diabetic foot ulcer (n = 22). Overall, the majority of indications were off-label (89/120, 74.2%), rather than in-label (complicated skin infections, bacteremia, endocarditis). The full list of infection sites reported in the included articles is available in Table 2, while full data on all described cases are reported in Table 3.

Table 2.

Site of infection described in the included articles, reported in order of frequency

Site of infectionn (patients %)
Osteomyelitis, septic arthritis, or spondylodiscitis 39 (32.5) 
Prosthetic joint infection 36 (30) 
Sepsis/bacteremia 23 (19.1) 
SSTI/wound infection/diabetic foot ulcer 22 (18.3) 
PVE/IE or aortic graft infection 13 (10.8) 
Abscess 8 (6.6) 
Surgical prophylaxis 2 (1.6) 
Pneumonia 1 (0.8) 
UTI 1 (0.8) 
Site of infectionn (patients %)
Osteomyelitis, septic arthritis, or spondylodiscitis 39 (32.5) 
Prosthetic joint infection 36 (30) 
Sepsis/bacteremia 23 (19.1) 
SSTI/wound infection/diabetic foot ulcer 22 (18.3) 
PVE/IE or aortic graft infection 13 (10.8) 
Abscess 8 (6.6) 
Surgical prophylaxis 2 (1.6) 
Pneumonia 1 (0.8) 
UTI 1 (0.8) 

SSTI, skin and soft tissue infection; PVE, prosthetic valve endocarditis; IE, infectious endocarditis; UTI, urinary tract infection.

Table 3.

Brief overview of all described cases

First author, year [ref]AgeGenderIndicationIsolateDose, mg/kg)/dTreatment duration, daysBALFDA classOutcome
Akabusi et al., 2022 [1646 Osteomyelitis MRSA NA 14 
Bhalla et al., 2022 [1768 Septic arthritis MRSA NA 21 
Sharma and Albujoq, 2022 [1880 Bacteremia, septic arthritis MRSA NA 14 
Mehern, 2022 [1979 SSTI, septic arthritis MRSA, VRE NA 21 
Sulaiman et al., 2022 [2063 Wound infection Bacteroides fragilis NA 21 
Fujii et al., 2022 [2182 PVE NA 23 
Ugalde et al., 2022 [2259 NA NA NA NA NA 
Haririan et al., 2022 [2358 Osteomyelitis NA NA 11 
Gonzales et al., 2022 [2473 Prosthetic joint infection, wound dehiscence NA NA 84 
Chan et al., 2022 [2545 Bacteremia Globicatella NA 14 
Bajwa and Palmar, 2022 [2679 Bacteremia MRSA NA 
Amjad et al., 2022 [2774 Osteomyelitis, bacteremia MRSA NA 
Fyffe and Blessing, 2021 [2869 Osteomyelitis NA NA 21 
Mukherjee and Sankaramangalam, 2021 [2965 Septic arthritis, bacteremia MRSA NA 21 
Sajid et al., 2021 [3066 Osteomyelitis NA NA 
Besmanos et al., 2021 61 Bacteremia, osteomyelitis, pneumonia MRSA NA NA NA 
Davenport and Blum, 2020 [3180 Cellulitis MRSA 19 
Zheng et al., 2019 [3281 Bacteremia, liver abscess Multiple NA 35 
Patel et al., 2019 [3381 Prosthetic joint infection MRSA + Proteus spp. NA 24 
Ghani et al., 2019 [3470 Bacteremia Staphylococcus aureus NA 21 
“ 50 Wound infection MRSA NA NA NA 
Rawal et al., 2019 [3574 Bacteremia, PVE MRSA NA 14 
Lelli et al., 2019 [3647 Bacteremia, endocarditis, osteomyelitis MSSA NA 19 
Yore et al., 2019 [3769 Surgical prophylaxis NA NA 11 
Yáñez Feria et al., 2018 [3881 Prosthetic joint infection MRSA 28 
Rasheed et al., 2018 [3954 Osteomyelitis NA NA 30 
Mazalewski et al., 2018 [4072 Endocarditis MRSA NA 42 
Iyer and Muthiah, 2018 [4165 Osteomyelitis MRSA NA 35 
Abdelkader and Singh, 2018 [4264 Bacteremia MRSA NA NA 3** 
Tachamo et al., 2018 [4389 Bacteremia, endocarditis CoNS NA 28 
Mingora, 2017 [4456 Cellulitis, myositis NA NA NA 
Ravi et al., 2017 [4562 Osteomyelitis NA NA 28 
Riehani et al., 2017 [4659 Osteomyelitis NA NA NA 
Rachid et al., 2017 [4764 SSTI MRSA NA 35 3** 
Shahangian et al., 2016 [4860 Sepsis, foot gangrene MRSA NA 14 
Olson et al., 2016 [4955 Bursitis MRSA NA 
Akcaer et al., 2016 [5060 SSTI MRSA 24 
Katz et al., 2016 [5160 Diskitis NA NA 14 
Hilal and Khosravi, 2015 [5272 Complicated UTI NA NA 14 
Kuchelan et al., 2015 [5360 Prosthetic joint infection NA NA NA 
Neyra et al., 2015 [5473 Endograft infection NA NA 
Roux et al., 2015 [5567 Prosthetic joint infection MSSA 17 
Chiu et al., 2015 [5677 Osteomyelitis S. aureus, VRE 42 
“ 74 Abscess NA 10 
Fisher et al., 2015 [5757 NA Multiple 10 3** 
Azam et al., 2014 [5865 Septic arthritis NA NA 14 
Folkard and Munoz, 2014 [5969 Prosthetic joint infection, bacteremia VRE NA NA 
Rajagopal et al., 2014 [6063 Cellulitis, diabetic foot ulcer NA NA 14 
Yamamoto et al., 2014 [6181 Bacteremia MRSA 10 16 
Keyt et al., 2013 [6228 Osteomyelitis Multiple NA 28 
Edukulla et al., 2014 [6372 Osteomyelitis NA NA 15 
Mehta et al., 2012 [6462 Osteomyelitis NA 28 3** 
Tolle and Hyzy, 2012 [6573 Thrombophlebitis, diskitis MRSA NA 42 
Chow et al., 2011 [6656 SSTI MRSA NA 14 
O'Brien, 2011 [6778 Abscess MRSA NA 14 
Prahl et al., 2010 [6864 Septic arthritis NA NA 42 
Lal and Assimacopoulos, 2010 [6982 Prosthetic joint infection MRCoNS NA 21 
“ 87 Prosthetic joint infection NA  28 
Shinde et al., 2009 [7054 SSTI MRSA NA 14 3** 
Kakish et al., 2008 [7165 Osteomyelitis, epidural abscess MRSA 
Cobb et al., 2007 [7284 Prosthetic joint infection MRSA 50 3** 
Sharma et al., 2023 [7365 Osteomyelitis NA NA 14 
Zou et al., 2023 [7444 Bacteremia MRSA 19 
Pham et al., 2022 [7579 Peri-prosthetic joint infection NA 8.6 23 
“ 67 Peri-prosthetic joint infection NA 17 
“ 68 Peri-prosthetic joint infection NA 5.6 16 
“ 76 Peri-prosthetic joint infection NA 7.9 39 
“ 58 Osteomyelitis NA 6.7 21 
“ 71 Ulcers NA 9.5 15 
“ 82 Peri-prosthetic joint infection NA 8.3 29 
“ 77 Peri-prosthetic joint infection NA 10.0 78 
“ 79 Peri-prosthetic joint infection NA 8.2 22 
“ 82 Peri-prosthetic joint infection NA 8.2 21 
“ 72 Osteomyelitis NA 10 16 
“ 78 Peri-prosthetic joint infection NA 7.2 3* 
“ 72 Peri-prosthetic joint infection NA 13 
“ 75 Osteomyelitis NA 7.5 18 
“ 92 Peri-prosthetic joint infection NA 8.3 24 
“ 70 Peri-prosthetic joint infection NA 9.1 12 
“ 78 Osteomyelitis NA 6.8 16 
Abd Algayoum et al., 2022 [7671 Bursitis MRSA NA 28 
Valaiyapathi et al., 2022 [7783 Prosthetic knee infection NA NA 28 
Somoza-Cano et al., 2021 [7879 Prosthetic knee infection NA 13 
Watts et al., 2021 [7965 Septic arthritis and bacteremia MRSA 21 
Raman et al., 2021 [8071 Endocarditis MRSA 10 14 
Portalatin et al., 2021 [353 Multiple paraspinous abscesses, bacteremia MRSA NA 30 
Storandt et al., 2020 [8156 Epidural abscess CoNS 14 
Fernández-González et al., 2021 [8292 Phlebitis, bacteremia MSSA 10 12 
Raza et al., 2019 [8372 Osteomyelitis MRSA NA 30 
Kumar et al., 2018 [8465 Osteomyelitis, epidural phlegmon MSSA NA 28 
Basnet et al., 2018 [8589 Bacteremia, endocarditis CoNS NA 28 
Abelenda Alonso et al., 2018 [8650 Surgical prophylaxis, bacteremia Klebsiella ESBL 23 
Rachid et al., 2017 [8764 SSTI MRSA 42 3** 
Raru et al., 2018 [8868 Septic arthritis CoNS NA 28 
Higashi et al., 2018 [8953 Cellulitis, osteomyelitis, bacteremia Multiple 7 q48h 24 
Nickerson et al., 2017 [9070 Osteomyelitis MRSA NA 11 
Hirai et al., 2017 [9164 Prosthetic joint infection MSSA 20 
“ 74 Prosthetic joint infection MRCoNS 5.8 24 
“ 77 Prosthetic joint infection MRCoNS 5.3 14 
“ 61 Diabetic foot ulcer MRSA 24 
“ 67 Spondylodiscitis MRSA 5.8 52 
“ 69 Wound infection MRSA 5.2 
Zaccarini and Dong, 2016 [9288 Prosthetic joint infection NA NA 21 
Hatipoglu et al., 2016 [9367 Diabetic foot ulcer MRSA 23 
Montenegro et al., 2015 [9454 Endocarditis MRSA 42 
Hagiya et al., 2015 [9534 Endocarditis MSSA 10 3* 
Patel et al., 2014 [9661 Osteomyelitis NA NA 
Yusuf et al., 2014 [9764 Prosthetic joint infection MRCoNS 10 28 
“ 61 Prosthetic joint infection MRCoNS 10 14 
Corona Pérez-Cardona et al., 2012 [9885 Prosthetic joint infection CoNS 35 
Rether et al., 2011 [9969 Spondylodiscitis, abscess Enterococcus faecium 21 
Kalogeropoulos et al., 2011 [10078 Endocarditis NA 10 
Søndergaard et al., 2010 [10175 Endocarditis E. faecalis NA 28 
Miller et al., 2010 [10260 Prosthetic joint infection MSSA 14 
“ 60 Osteomyelitis MRSA 14 
“ 83 Diskitis NA 28 3** 
Hayes et al., 2007 [760 Endocarditis MSSA NA 13 
Eckhardt et al., 2022 [103NA NA Wound and implant infection Multiple NA 29 
Patel et al., 2022 [10477 Osteomyelitis MRSA NA 13 
Zimmer et al., 2020 [10569 Prosthetic joint infection Multiple 10 3* 
First author, year [ref]AgeGenderIndicationIsolateDose, mg/kg)/dTreatment duration, daysBALFDA classOutcome
Akabusi et al., 2022 [1646 Osteomyelitis MRSA NA 14 
Bhalla et al., 2022 [1768 Septic arthritis MRSA NA 21 
Sharma and Albujoq, 2022 [1880 Bacteremia, septic arthritis MRSA NA 14 
Mehern, 2022 [1979 SSTI, septic arthritis MRSA, VRE NA 21 
Sulaiman et al., 2022 [2063 Wound infection Bacteroides fragilis NA 21 
Fujii et al., 2022 [2182 PVE NA 23 
Ugalde et al., 2022 [2259 NA NA NA NA NA 
Haririan et al., 2022 [2358 Osteomyelitis NA NA 11 
Gonzales et al., 2022 [2473 Prosthetic joint infection, wound dehiscence NA NA 84 
Chan et al., 2022 [2545 Bacteremia Globicatella NA 14 
Bajwa and Palmar, 2022 [2679 Bacteremia MRSA NA 
Amjad et al., 2022 [2774 Osteomyelitis, bacteremia MRSA NA 
Fyffe and Blessing, 2021 [2869 Osteomyelitis NA NA 21 
Mukherjee and Sankaramangalam, 2021 [2965 Septic arthritis, bacteremia MRSA NA 21 
Sajid et al., 2021 [3066 Osteomyelitis NA NA 
Besmanos et al., 2021 61 Bacteremia, osteomyelitis, pneumonia MRSA NA NA NA 
Davenport and Blum, 2020 [3180 Cellulitis MRSA 19 
Zheng et al., 2019 [3281 Bacteremia, liver abscess Multiple NA 35 
Patel et al., 2019 [3381 Prosthetic joint infection MRSA + Proteus spp. NA 24 
Ghani et al., 2019 [3470 Bacteremia Staphylococcus aureus NA 21 
“ 50 Wound infection MRSA NA NA NA 
Rawal et al., 2019 [3574 Bacteremia, PVE MRSA NA 14 
Lelli et al., 2019 [3647 Bacteremia, endocarditis, osteomyelitis MSSA NA 19 
Yore et al., 2019 [3769 Surgical prophylaxis NA NA 11 
Yáñez Feria et al., 2018 [3881 Prosthetic joint infection MRSA 28 
Rasheed et al., 2018 [3954 Osteomyelitis NA NA 30 
Mazalewski et al., 2018 [4072 Endocarditis MRSA NA 42 
Iyer and Muthiah, 2018 [4165 Osteomyelitis MRSA NA 35 
Abdelkader and Singh, 2018 [4264 Bacteremia MRSA NA NA 3** 
Tachamo et al., 2018 [4389 Bacteremia, endocarditis CoNS NA 28 
Mingora, 2017 [4456 Cellulitis, myositis NA NA NA 
Ravi et al., 2017 [4562 Osteomyelitis NA NA 28 
Riehani et al., 2017 [4659 Osteomyelitis NA NA NA 
Rachid et al., 2017 [4764 SSTI MRSA NA 35 3** 
Shahangian et al., 2016 [4860 Sepsis, foot gangrene MRSA NA 14 
Olson et al., 2016 [4955 Bursitis MRSA NA 
Akcaer et al., 2016 [5060 SSTI MRSA 24 
Katz et al., 2016 [5160 Diskitis NA NA 14 
Hilal and Khosravi, 2015 [5272 Complicated UTI NA NA 14 
Kuchelan et al., 2015 [5360 Prosthetic joint infection NA NA NA 
Neyra et al., 2015 [5473 Endograft infection NA NA 
Roux et al., 2015 [5567 Prosthetic joint infection MSSA 17 
Chiu et al., 2015 [5677 Osteomyelitis S. aureus, VRE 42 
“ 74 Abscess NA 10 
Fisher et al., 2015 [5757 NA Multiple 10 3** 
Azam et al., 2014 [5865 Septic arthritis NA NA 14 
Folkard and Munoz, 2014 [5969 Prosthetic joint infection, bacteremia VRE NA NA 
Rajagopal et al., 2014 [6063 Cellulitis, diabetic foot ulcer NA NA 14 
Yamamoto et al., 2014 [6181 Bacteremia MRSA 10 16 
Keyt et al., 2013 [6228 Osteomyelitis Multiple NA 28 
Edukulla et al., 2014 [6372 Osteomyelitis NA NA 15 
Mehta et al., 2012 [6462 Osteomyelitis NA 28 3** 
Tolle and Hyzy, 2012 [6573 Thrombophlebitis, diskitis MRSA NA 42 
Chow et al., 2011 [6656 SSTI MRSA NA 14 
O'Brien, 2011 [6778 Abscess MRSA NA 14 
Prahl et al., 2010 [6864 Septic arthritis NA NA 42 
Lal and Assimacopoulos, 2010 [6982 Prosthetic joint infection MRCoNS NA 21 
“ 87 Prosthetic joint infection NA  28 
Shinde et al., 2009 [7054 SSTI MRSA NA 14 3** 
Kakish et al., 2008 [7165 Osteomyelitis, epidural abscess MRSA 
Cobb et al., 2007 [7284 Prosthetic joint infection MRSA 50 3** 
Sharma et al., 2023 [7365 Osteomyelitis NA NA 14 
Zou et al., 2023 [7444 Bacteremia MRSA 19 
Pham et al., 2022 [7579 Peri-prosthetic joint infection NA 8.6 23 
“ 67 Peri-prosthetic joint infection NA 17 
“ 68 Peri-prosthetic joint infection NA 5.6 16 
“ 76 Peri-prosthetic joint infection NA 7.9 39 
“ 58 Osteomyelitis NA 6.7 21 
“ 71 Ulcers NA 9.5 15 
“ 82 Peri-prosthetic joint infection NA 8.3 29 
“ 77 Peri-prosthetic joint infection NA 10.0 78 
“ 79 Peri-prosthetic joint infection NA 8.2 22 
“ 82 Peri-prosthetic joint infection NA 8.2 21 
“ 72 Osteomyelitis NA 10 16 
“ 78 Peri-prosthetic joint infection NA 7.2 3* 
“ 72 Peri-prosthetic joint infection NA 13 
“ 75 Osteomyelitis NA 7.5 18 
“ 92 Peri-prosthetic joint infection NA 8.3 24 
“ 70 Peri-prosthetic joint infection NA 9.1 12 
“ 78 Osteomyelitis NA 6.8 16 
Abd Algayoum et al., 2022 [7671 Bursitis MRSA NA 28 
Valaiyapathi et al., 2022 [7783 Prosthetic knee infection NA NA 28 
Somoza-Cano et al., 2021 [7879 Prosthetic knee infection NA 13 
Watts et al., 2021 [7965 Septic arthritis and bacteremia MRSA 21 
Raman et al., 2021 [8071 Endocarditis MRSA 10 14 
Portalatin et al., 2021 [353 Multiple paraspinous abscesses, bacteremia MRSA NA 30 
Storandt et al., 2020 [8156 Epidural abscess CoNS 14 
Fernández-González et al., 2021 [8292 Phlebitis, bacteremia MSSA 10 12 
Raza et al., 2019 [8372 Osteomyelitis MRSA NA 30 
Kumar et al., 2018 [8465 Osteomyelitis, epidural phlegmon MSSA NA 28 
Basnet et al., 2018 [8589 Bacteremia, endocarditis CoNS NA 28 
Abelenda Alonso et al., 2018 [8650 Surgical prophylaxis, bacteremia Klebsiella ESBL 23 
Rachid et al., 2017 [8764 SSTI MRSA 42 3** 
Raru et al., 2018 [8868 Septic arthritis CoNS NA 28 
Higashi et al., 2018 [8953 Cellulitis, osteomyelitis, bacteremia Multiple 7 q48h 24 
Nickerson et al., 2017 [9070 Osteomyelitis MRSA NA 11 
Hirai et al., 2017 [9164 Prosthetic joint infection MSSA 20 
“ 74 Prosthetic joint infection MRCoNS 5.8 24 
“ 77 Prosthetic joint infection MRCoNS 5.3 14 
“ 61 Diabetic foot ulcer MRSA 24 
“ 67 Spondylodiscitis MRSA 5.8 52 
“ 69 Wound infection MRSA 5.2 
Zaccarini and Dong, 2016 [9288 Prosthetic joint infection NA NA 21 
Hatipoglu et al., 2016 [9367 Diabetic foot ulcer MRSA 23 
Montenegro et al., 2015 [9454 Endocarditis MRSA 42 
Hagiya et al., 2015 [9534 Endocarditis MSSA 10 3* 
Patel et al., 2014 [9661 Osteomyelitis NA NA 
Yusuf et al., 2014 [9764 Prosthetic joint infection MRCoNS 10 28 
“ 61 Prosthetic joint infection MRCoNS 10 14 
Corona Pérez-Cardona et al., 2012 [9885 Prosthetic joint infection CoNS 35 
Rether et al., 2011 [9969 Spondylodiscitis, abscess Enterococcus faecium 21 
Kalogeropoulos et al., 2011 [10078 Endocarditis NA 10 
Søndergaard et al., 2010 [10175 Endocarditis E. faecalis NA 28 
Miller et al., 2010 [10260 Prosthetic joint infection MSSA 14 
“ 60 Osteomyelitis MRSA 14 
“ 83 Diskitis NA 28 3** 
Hayes et al., 2007 [760 Endocarditis MSSA NA 13 
Eckhardt et al., 2022 [103NA NA Wound and implant infection Multiple NA 29 
Patel et al., 2022 [10477 Osteomyelitis MRSA NA 13 
Zimmer et al., 2020 [10569 Prosthetic joint infection Multiple 10 3* 

BAL, bronchoalveolar lavage; FDA Food and Drug Administration (class 1: possible, class 2: probable, class 3: definite); M, male gender; MRSA, methicillin-resistant Staphylococcus aureus; NA, not available; Y, yes; R, recovery; VRE, vancomycin-resistant Enterococcus; N, no; SSTI, skin and soft tissue infection; D, death; F, female gender; CoNS, coagulase-negative Staphylococcus; MRCoNS, methicillin-resistant coagulase-negative Staphylococcus; ESBL, extended spectrum beta-lactamase producer; FDA, Food and Drug Administration; MSSA, methicillin-sensitive Staphylococcus aureus; PVE, prosthetic valve endocarditis; UTI, urinary tract infection. *after re-exposure; **bioptic sample.

Antimicrobial Regimen and Microbial Isolates

When microbiological data were available (74/120 cases), isolated pathogens most frequently included gram-positive cocci, the most represented being methicillin-resistant S. aureus (53.8%), methicillin-sensitive S. aureus (2.8%), and coagulase-negative Staphylococci (12.8%); vancomycin-resistant Enterococcus or polymicrobial infections were reported in 5.1% of the cases each. The exact distribution of isolated pathogens can be found in Table 4.

Table 4.

Isolated pathogens described in the included articles, reported in order of frequency (n = 74)

Isolated pathogenN (%)
MRSA 42 (56.7) 
MSSA 10 (13.5) 
CoNS 10 (13.5) 
VRE 4 (5.4) 
Polymicrobial 4 (5.4) 
Globicatella 
Bacteroides fragilis 
Penicillin-resistant Streptococcus mitis 
Klebsiella (ESBL) 
Streptococcus agalactiae 
Enterococcus faecium 
E. faecalis 
Proteus 
Isolated pathogenN (%)
MRSA 42 (56.7) 
MSSA 10 (13.5) 
CoNS 10 (13.5) 
VRE 4 (5.4) 
Polymicrobial 4 (5.4) 
Globicatella 
Bacteroides fragilis 
Penicillin-resistant Streptococcus mitis 
Klebsiella (ESBL) 
Streptococcus agalactiae 
Enterococcus faecium 
E. faecalis 
Proteus 

MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; VRE, vancomycin-resistant Enterococcus; ESBL, extended spectrum beta-lactamase; CoNS, coagulase-negative Staphylococcus.

Daptomycin Posology, Timing of Symptom Onset, Diagnosis, and Clinical Outcome

The majority of the included articles did not report information on daptomycin dosing. When reported, daptomycin posology ranged between 4 mg/kg/die and 10 mg/kg/die. The onset of symptoms suggestive for eosinophilic pneumonia was reported after a mean of 21.75 (SD ± 12.91) days of treatment (range 3–84 days). Symptoms usually included fever, dyspnea, and dry cough. Less frequently reported symptoms included chest pain, altered mental status, upper respiratory tract symptoms, and hypertension. All reported symptoms are available in Table 5.

Table 5.

Reported symptoms, in order of frequency

SymptomsN (%)
Dyspnea 83 (69.16) 
Fever 72 (60.00) 
Cough 58 (48.33) 
Respiratory failure 34 (28.33) 
Tachypnea/tachycardia/palpitations 11 (9.16) 
Fatigue/lethargy 9 (7.50) 
Myalgias/chills 7 (5.83) 
Altered mental status/depressed mood 3 (2.50) 
Chest pain 3 (2.50) 
Rhinorrhea, pharyngodynia 1 (0.83) 
Hypertension 1 (0.83) 
SymptomsN (%)
Dyspnea 83 (69.16) 
Fever 72 (60.00) 
Cough 58 (48.33) 
Respiratory failure 34 (28.33) 
Tachypnea/tachycardia/palpitations 11 (9.16) 
Fatigue/lethargy 9 (7.50) 
Myalgias/chills 7 (5.83) 
Altered mental status/depressed mood 3 (2.50) 
Chest pain 3 (2.50) 
Rhinorrhea, pharyngodynia 1 (0.83) 
Hypertension 1 (0.83) 

Daptomycin-induced AEP was hypothesized based on clinical suspicion, usually required an imaging technique, such as chest CT scan, and was confirmed with BAL in 57.5% (n.69/120) of the cases. Following the abovementioned FDA diagnostic criteria, a definite diagnosis was made via BAL or bioptic sample in 40.17% of the cases (n.42/117). Of these, 5 (4.2%) received a definite diagnosis through examination of a bioptic sample, while the remainder (95.8%) had their formal diagnosis confirming eosinophil hyper-representation on BAL samples. Sixty-four patients (53.3%) were classified as probable daptomycin-induced AEP, while 11 cases (9.1%) were classified as possible. In 2 cases, AEP appeared after a very short drug exposure (3 days). Interestingly, in both cases patients were already exposed to daptomycin, but did not develop AEP during the first course of therapy. Four patients died (3.3%) either due to respiratory failure (3/4) or secondarily due to complications related to the initial pathology. The remaining 116 patients recovered after daptomycin withdrawal and respiratory support and corticosteroid treatment.

Risk of Bias of Included Studies

A formal appraisal of the included observational studies was performed by means of NOS. Both observational studies had high quality, collecting 9/9 points each. Detailed results are available in the online supplementary material Table S2.

Here, we discuss a case of daptomycin-induced AEP, formally classifiable as possible AEP according to FDA diagnostic criteria [10]. This case could be of interest to other clinicians when assessing possible causes for a sudden worsening of respiratory function following prolonged daptomycin administration. In the context of differential diagnosis of eosinophilic pneumonias and in accordance with the diagnostic criteria established by the FDA [10] and those proposed by Solomon and Schwarz [5], the primary examinations and procedures necessary to diagnose AEP include chest radiographic imaging, such as chest X-ray or CT scans, as well as BAL fluid examination, in which eosinophil levels should be assessed.

Peripheral eosinophil count may also aid in confirming the potential diagnosis. Furthermore, the diagnosis of AEP could be delayed in the effort of looking for other pathogens as possible causes for the respiratory distress, therefore prolonging the exposure to the causative agent. This was the case of our patient: only when pulmonary infection was ruled out, we considered daptomycin as a putative responsible, allowing for a prompt recovery after its discontinuation.

Our systematic review of the literature identified 93 articles reporting similar cases. We did not find studies designed or specifically powered to estimate the incidence of a rare side effect such as AEP, and most of the literature included in our review is composed by conference abstract/poster and case reports (80/93). Though this could limit publication bias, the present selection of included articles could result in a misinterpretation of the risk, both overrepresenting its true incidence and at the same time underestimating this potentially fatal side effect. We think these two elements could represent both a strength and a limitation of the present study.

Daptomycin was mostly used off-label (89/120, 74.1%), for infections other than the in-label indications of complicated skin infections, bloodstream infection, and endocarditis [8, 9]. This undoubtingly proves daptomycin versatility and applications in various clinical settings, but should prompt a discussion on daptomycin use in long treatments such as for osteomyelitis, spondylodiscitis, or prosthetic joint infection. The need for longer drug exposure increases the risk of developing AEP, since chronic daptomycin administration results in drug accumulation on the epithelial alveolar surface, resulting in epithelial cell injury and in an alteration of cell lipid integrity, causing a sustained inflammatory response [4, 9, 106]. In the included literature, the median time of daptomycin exposure before AEP onset was 21.75 days (range 3–84 days). Interestingly, 3 cases reported the onset of daptomycin-induced AEP shortly after the third day of exposure but actually all patients had been previously exposed to daptomycin, suggesting a priming immunologic effect. Hagiya et al. [95] reported a case of patient who developed AEP after the third day of daptomycin administration. This very short treatment regimen was in fact a re-exposure for the patient, being the primary challenge 20 days earlier [95]. Zimmer et al. [105] reported a similar case, in which the patient presented a daptomycin-induced AEP with sudden respiratory distress 9 days after a 3-day re-challenge of daptomycin, 2 weeks after priming. A third case by Pham et al. reported an AEP upon re-exposure to daptomycin firstly occurred 6 months prior [75].

As reported by previous literature, re-challenge to a drug or a toxin after primary exposure carries an intrinsic risk for lung immune-mediated damage [5, 107]. Reported cases are consistent with the hypothesis stating this side effect could be mediated by the accumulation of daptomycin-related degradation products in the alveoli, where surfactant acts as an inflammatory trigger and as chemotactic agent [3]. Our search identified 4 cases of fatal outcomes during the treatment of AEP. Among these, Ugalde et al. reported a case of early discontinuation of corticosteroid treatment complicated by the development of tension pneumothorax and pneumomediastinum, in turn resulting in patient death [22]. Haririan and colleagues reported a fatal case of daptomycin-induced AEP after an initial recovery. Autopsy showed diffuse alveolar damage compatible with daptomycin-mediated damage [23]. Edukulla et al. [63] reported a fatal outcome secondary to heart failure, not necessarily attributable to daptomycin-induced AEP. The case described by Raman and colleagues died after worsening of clinical conditions, not exclusively due to complications related to daptomycin-induced AEP [80].

Most cases reported daptomycin administration in the treatment of gram-positive bacteria, while only in 3 cases the drug was administered to treat a combined gram-positive/gram-negative bacteria (Bacteroides fragilis, Klebsiella spp., P. mirabilis) [20, 33, 86]. In these, daptomycin was used in the suspect of an unidentified gram-positive co-infection, receiving not only daptomycin but also a carbapenem as a main antibiotic in order to treat the reported gram-negative infection.

Fever, dyspnea, and dry cough were the most frequently reported symptoms prompting radiological tests (chest X-ray or CT) to rule out bacterial or fungal pneumonia. As in our case report, compiling a well-designed differential diagnosis algorithm is essential. As shown by the Naranjo algorithm, the exclusion of all other possible causes for a clinical situation should prompt the suspicion of a drug-induced disease [108].

Daptomycin-induced eosinophilic pneumonia is a rare but potentially fatal side effect that should not be overlooked by clinicians. After excluding fungal or nematode infection and systemic immunologic diseases as eosinophilic granulomatosis with polyangiitis, drug-induced eosinophilic pneumonia has to be included in the differential, because of its potentially fatal effect. Despite its rarity, daptomycin-induced AEP should be acknowledged when using daptomycin for indications with long treatment, such as osteomyelitis, considering a potentially fatal risk of AEP if daptomycin-induced AEP is not promptly suspected. Further investigation is needed for a better understanding of the pathogenic mechanism of daptomycin-induced AEP and to verify the duration of the priming effect of primary exposure after the first course of administration.

This retrospective review of patient data did not require ethical approval in accordance with national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. As for the systematic review of the literature, an ethics statement is not applicable because this study is based exclusively on published literature.

L.S. reports honoraria for lectures and research grants from Merk, Gilead, AbbVie, and Angelini SpA. M.A. reports honoraria for lectures and research grants from Merk, Gilead, AbbVie, and Angelini SpA. M.I. received honoraria for lectures from Biogen Italia, AIM Educational, MICOM srl, and Roche SpA. The remaining authors declare that they have no known conflicts of interest.

This research received no external funding.

A.D.L., L.V.R., and L.S. performed all phases of the systematic review. L.C., A.I., G.A., P.G.P., A.L., B.R., A.M.A.C., P.V., D.K., V.M., M.A., and M.I. were involved in the care of the described patient. All authors have read and agreed to the published version of the manuscript.

All included data are available in the present record and shown in tables and figures. Additional information about the reported case is available upon request by contacting the corresponding author.

1.
Badesch DB, King TE, Schwarz MI. Acute eosinophilic pneumonia: a hypersensitivity phenomenon?Am Rev Respir Dis. 1989;139(1):249–52.
2.
Allen JN, Pacht ER, Gadek JE, Davis WB. Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure. N Engl J Med. 1989;321(9):569–74.
3.
Portalatin GM, Chin J-A, Foster B, Perry K, McWilliams C. Daptomycin-induced acute eosinophilic pneumonia. Cureus. 2021;13(2):e13509.
4.
Uppal P, LaPlante KL, Gaitanis MM, Jankowich MD, Ward KE. Daptomycin-induced eosinophilic pneumonia - a systematic review. Antimicrob Resist Infect Control. 2016;5:55.
5.
Solomon J, Schwarz M. Drug-Toxin-and radiation therapy-induced eosinophilic pneumonia. Semin Respir Crit Care Med. 2006;27(2):192–7.
6.
Kim PW, Sorbello AF, Wassel RT, Pham TM, Tonning JM, Nambiar S. Eosinophilic pneumonia in patients treated with daptomycin: review of the literature and US FDA adverse event reporting system reports. Drug Saf. 2012;35(6):447–57.
7.
Hayes D, Anstead MI, Kuhn RJ. Eosinophilic pneumonia induced by daptomycin. J Infect. 2007;54(4):e211–3.
8.
Lipsky BA, Stoutenburgh U. Daptomycin for treating infected diabetic foot ulcers: evidence from a randomized, controlled trial comparing daptomycin with vancomycin or semi-synthetic penicillins for complicated skin and skin-structure infections. J Antimicrob Chemother. 2005;55(2):240–5.
9.
Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, et al. 2015 infectious diseases society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61(6):e26–46.
10.
CUBICIN (daptomycin for injection) for intravenous use.
11.
Silverman JA, Mortin LI, VanPraagh ADG, Li T, Alder J. Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis. 2005;191(12):2149–52.
12.
Barber KE, Shammout Z, Smith JR, Kebriaei R, Morrisette T, Rybak MJ. Biofilm time-kill curves to assess the bactericidal activity of daptomycin combinations against biofilm-producing vancomycin-resistant Enterococcus faecium and faecalis. Antibiotics. 2021;10(8):897.
13.
Boudjemaa R, Briandet R, Revest M, Jacqueline C, Caillon J, Fontaine-Aupart M-P, et al. New insight into daptomycin bioavailability and localization in Staphylococcus aureus biofilms by dynamic fluorescence imaging. Antimicrob Agents Chemother. 2016;60(8):4983–90.
14.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
15.
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan: a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210.
16.
Akabusi CW, A Torres M, Choudry SA, I Ojeda-Martinez H. Daptomycin-induced eosinophilic pneumonitis. Chest. 2022;162(4):A1773.
17.
Bhalla V, Iyer C, Obaji A. Toxic to the lungs: a case of daptomycin-induced acute eosinophilic pneumonia. Chest. 2022;162(4):A1303.
18.
Sharma R, Albujoq K. A tale of a drug that killed a bug but caused pneumonia: a case report of daptomycin induced eosinophilic pneumonia. In: Proceedings of the b36. the good, the bad, and the ugly: drug toxicity case reports. American Thoracic Society; 2023. p. A3187.
19.
Mehern K, Bachan M, Khan Z. A unique case: acute eosinophilic pneumonia secondary to daptomycin: a COVID-19 pneumonia mimic. Chest. 2022;162(4):A1868.
20.
Sulaiman ZI, Z Holland L, R Fox N. AN unusual case of acute eosinophilic pneumonia complicated by daptomycin. Chest. 2022;162(4):A1204.
21.
Fujii E, Arita T, Uejima T, Matsuhama M, Iida M, Inoue T, et al. Blood culture-negative prosthetic valve endocarditis and daptomycin-associated eosinophilic pneumonia: a case report. J Cardiol Cases. 2022;25(6):354–8.
22.
Ugalde IC, Van Nostrand K, Qureshi MR, Floreth TJ. A not-so-common cause of chest pain and shortness of breath. In: Proceedings of the a37. Case reports: drug toxicity. American Thoracic Society; 2022. p. A1395.
23.
Haririan P, Silberstein DJ, Natarajan S. A rare case of fatal daptomycin induced interstitial pneumonia. In: Proceedings of the a37. Case reports: drug toxicity. American Thoracic Society; 2022. p. A1404.
24.
Gonzalez M, Mahapatra S, Gillenwater S, Lorenzana AM, Mehta JP. Daptomycin-induced acute eosinophilic pneumonia. In: Proceedings of the a37. Case reports: drug toxicity. American Thoracic Society; 2022. p. A1406.
25.
Chan R, Sakhamuri P, Walker S. Daptomycin-induced eosinophilic pneumonia. In: Proceedings of the A37. Case reports: drug toxicity. American Thoracic Society; 2022. p. A1411.
26.
Bajwa A, Parmar M. Daptomycin induced eosinophilic pneumonia. In: Proceedings of the a37. Case reports: drug toxicity. American Thoracic Society; 2022. p. A1418.
27.
Amjad MA, Hamid Z, Patel Y, Raheja V, Ochieng PO. Drug-induced lung disease: who is the culprit? In: Proceedings of the A23. Case reports in ILD and lung transplantation. American Thoracic Society; 2022. p. A1105.
28.
Fyffe Z, Blessing R. Suspected daptomycin-induced eosinophillic pneumonia. Chest. 2021;160(4):A747.
29.
Mukherjee A, Sankaramangalam K. A case of daptomycin induced acute eosinophilic pneumonia in a patient with septic arthritis.In Proceedings of the TP36. TP036 what drug caused that? Case reports in drug-induced lung disease. American Thoracic Society; 2021. p. A2154.
30.
Sajid F, Prudenti J, Hashemi Z. Dangerous side of daptomycin. In: Proceedings of the TP36. TP036 What drug caused that? Case reports in drug-induced lung disease. American Thoracic Society; 2021. p. A2155–A2155.
31.
Blum S, DL. Acute eosinophilic pneumonia secondary to daptomycin therapy: a case report. Internet J Pulm Med. 2020;20.
32.
Zheng S. An elderly man with fever, dyspnoea and eosinophilia. Eur J Intern Med. 2019;65:e5–6.
33.
Patel R, MBA rare cause of respiratory failure: daptomycin induced acute eosinophilic pneumonia. Am J Respir Crit Care Med. 2019;199:A6262.
34.
Ghani MU, Hashemi H, Behre M. Two cases of daptomycin-induced acute eosinophilic pneumonia. In: Proceedings of the A39. drug related case reports. American Thoracic Society; 2019. p. A1506.
35.
Rawal H, Sagheer U, Bhandari BS, Selinger SR. Daptomycin induced acute eosinophilic pneumonia: a case report. In: Proceedings of the A39. drug related case reports. American Thoracic Society; 2019. p. A1474.
36.
Lelli MW, Aldred LW, Wilhelm A. MSSA bacteremia complicated by suspected daptomycin-induced eosinophilic pneumonia. J Invest Med. 2019.
37.
Proceedings of the intern section of the Royal Academy of Medicine in Ireland (RAMI) venue: mater, Dublin 7 on Saturday 2nd February 2019. Ir J Med Sci. 2019;188:31–127.
38.
Feria DY, Rey MC, Gomez ES, Saiz SG, Martin CB. 5PSQ-042 acute eosinophilic pneumonia secondary to daptomycin: a case report. In: Proceedings of the Section 5: patient safety and quality assurance. British Medical Journal Publishing Group; 2018. p. A183.2.
39.
Rasheed A, Shahzadi M, Gerolemou L, Vasudevan V. 1033: differentials make a difference in a patient with severe hypoxemic respiratory failure. Crit Care Med. 2018;46(1):500.
40.
Mazalewski WR. When antibiotics induce pyrexia and dyspnea. J Gen Intern Med. 2018;33(2 Suppl 1):665–666.
41.
Iyer P, MMP. Daptomycin induced eosinophilic pneumonitis: a rare entity. Am J Respir Crit Care Med. 2018;197:A6583.
42.
Abdelkader M. S.V. Dyspnea While on Daptomycin. Am J Respir Crit Care Med. 2018;197:MeetingAbstracts.
43.
Tachamo N, Timilsina B, Mohanty E, Lohani S, Nazir S. Not All Pneumonia Is Infectious! J Hosp Med. 2018;13(4 Suppl 1).
44.
Mingora C. Suspected daptomycin-associated acute eosinophilic pneumonia with rapidly progressive hypoxemic respiratory failure: a case report. Chest. 2017;152(4):A469.
45.
Ravi V, Srinivasan L, Khurana A, Davuluri S, Fulambarker A, Copur A, et al. Daptomycin-induced severe ARDS: a therapeutic nightmare. Chest. 2017;152(4):A273.
46.
Riehani A, Cooke G, Stewart J, Sharma M. Daptomycin-Induced Eosinophilic Pneumonia. Am J Respir Crit Care Med. 2017;195.
47.
Rachid M, Ahmad K, Shah A, Nahhas A.Daptomycin-induced acute eosinophilic pneumonia: a treatble serious side effect. Am J Respir Crit Care Med. 2017;195.
48.
Shahangian S, Spier A, Chang D. Daptomycin-induced eosinophilic pneumonia in renal dysfunction. Chest. 2016;150(4):505A.
49.
Olson K, Kayani A, Saggar R. Acute eosinophilic pneumonia complicated by daptomycin. Chest. 2016;150(4):462A.
50.
Akcaer M, Karakas A, Tok D, Coskun O, Sari S. Eosinophilic pneumonia: daptomycin-induced lung complication; 2016.
51.
Katz A, Umpierrez De Reguero AP, Jha P. Daptomycin induced eosinophilic pneumonia. J Gen Intern Med. 2016;31(suppl 1):S592.
52.
Hilal T, Khosravi M. Daptomycin-induced acute eosinophilic pneumonia. Am J Respir Crit Care Med. 2015.
53.
Kuchelan D, Ie S, Foroozesh M. Daptomycin: a Pulmonary Foe. Am J Respir Crit Care Med. 2015;191:MeetingAbstracts.
54.
Neyra K, Rahman A, Gupta V, Cohen Z, Nafees Q. Acute eosinophilic pneumonia due to exposure to daptomycin leading to ventilator-dependent respiratory failure. Chest. 2015;148(4):635A.
55.
Roux S, Ferry T, Chidiac C, Valour F. Daptomycin-induced eosinophilic pneumonia. Int J Infect Dis. 2015;37:95–6.
56.
Chiu S-Y, Faust AC, Dand HM. Daptomycin-induced eosinophilic pneumonia treated with intravenous corticosteroids. J Pharm Pract. 2015;28(3):275–9.
57.
Fisher LH, Choi J, Bricker RS, Shere-Wolfe KD, Saharia K. A 57-year-old man with dyspnea and cough: figure 1. Clin Infect Dis. 2015;61(6):1026–7.
58.
Azam M, Asghar S, Jain R, Aggen D, Zakaria K, Kumar S. Acute eosinophilic pneumonia: a rare side effect of daptomycin. Chest. 2014;146(4):179A.
59.
Folkard C, Munoz R, Daptomycin-induced eosinophilic pneumonitis. J Gen Intern Med. 2014;29(suppl 1):S341-2.
60.
Rajagopal A, Mintz E, Reese L. Daptomycin-induced eosinophilic pneumonia without peripheral eosinophilia. Chest. 2014;145(3):127A.
61.
Yamamoto K, Hayakawa K, Ohmagari N. Daptomycin-induced pneumonitis in a patient with Chronic Obstructive Pulmonary Disease (COPD). Intern Med. 2014;53(21):2559–60.
62.
Keyt HL, Payan H, Peters JI, The challenge of recognizing adverse reactions to novel therapies. Am J Respir Crit Care Med. 2015;187:MeetingAbstracts.
63.
Edukulla J, Choudhary S, Glick A, DeSouza D. Eosinophilic pneumonia, rare but fatal side effect of daptomycin: a case report. J Gen Intern Med. 2014;28(suppl 1):S324.
64.
Mehta P, Wong W, Ramalingam S, Aucoin P, Chandak T. Daptomycin-induced acute eosinophilic pneumonia: an emerging clinical entity. Chest. 2012;142(4):1042A.
65.
Tolle LB, Hyzy RC. A 73-year-old man with acute eosinophilic pneumonia owing to daptomycin. Am J Respir Crit Care Med. 2012;185:MeetingAbstracts.
66.
Chow L, Gorga J, Zein J. Development of new pulmonary infiltrates in a patient treated with daptomycin. Chest. 2011;140(4):159A.
67.
O’Brien C. Research, innovations, clinical vignettes competition. Hosp Med. 2011;6:S1–282.
68.
Prahl JD, Tripp MS, Stafford CM. Organizing pneumonia and pneumothorax associated with daptomycin use. Chest. 2010;138(4):77A.
69.
Lal Y, Assimacopoulos AP. Two cases of daptomycin-induced eosinophilic pneumonia and chronic pneumonitis. Clin Infect Dis. 2010;50(5):737–40.
70.
Shinde A, Seifi A, DelRe S, Moustafa Hussein WH, Ohebsion J. Daptomycin-induced pulmonary infiltrates with eosinophilia. J Infect. 2009;58(2):173–4.
71.
Kakish E, Wiesner AM, Winstead PS, Bensadoun ES. Acute respiratory failure due to daptomycin induced eosinophilic pneumonia. Respir Med CME. 2008;1(3):235–7.
72.
Cobb E, Kimbrough RC, Nugent KM, Phy MP. Organizing pneumonia and pulmonary eosinophilic infiltration associated with daptomycin. Ann Pharmacother. 2007;41(4):696–701.
73.
Sharma S, Rojas H, Spano C, George-Varghese B, Liu T. Acute eosinophilic pneumonia presenting as altered mental status. J Emerg Med. 2023;64(4):502–5.
74.
Zou J, Rivera Sarti JE, Strasfeld L. Daptomycin associated pulmonary toxicity sans eosinophilia in a hematopoietic cell transplant recipient with profound leukopenia. Transpl Infect Dis. 2023;25(3):e14029.
75.
Pham T-T, Garreau R, Craighero F, Cottin V, Said BB, Goutelle S, et al. Seventeen cases of daptomycin-induced eosinophilic pneumonia in a cohort of patients treated for bone and joint infections: proposal for a new algorithm. Open Forum Infect Dis. 2022;9(11):ofac577.
76.
Abd Algayoum R, Elsherif A, Khan ZH, Roman G. Daptomycin-induced eosinophilic pneumonia mimicking multifocal pneumonia. Cureus. 2022;14(10):e30521.
77.
Valaiyapathi R, Wu M-S, McGregor A. Ground glass opacities are not always COVID-19: a case of acute eosinophilic pneumonitis caused by daptomycin. Lancet. 2022;399(10321):270.
78.
Somoza-Cano FJ, Makadia A, Cruz-Peralta MP, Zakarna L, Demyda E, Al Armashi AR, et al. Acute eosinophilic pneumonia secondary to daptomycin. Cureus. 2021;13(11):e19403.
79.
Watts A, Toquica Gahona CC, Raj K. Multifocal pneumonia amidst the global COVID-19 pandemic: a case of daptomycin-induced eosinophilic pneumonia. Cureus. 2021;13(6):e16002.
80.
Raman V, Chaudhary I, Shieh S. Eosinophilic pneumonia: a case of daptomycin induced lung injury. J Community Hosp Intern Med Perspect. 2021;11(2):280–5.
81.
Storandt MH, Matta A. Acute eosinophilic pneumonia: a rare complication of daptomycin therapy. Cureus. 2020;12(1):e6803.
82.
Fernández-González R, Díaz López MD, Lorenzo Vizcaya AM, González Noya A. Daptomycin associated eosinophilic pneumonia. Med Clin. 2021;156(3):148–9.
83.
Raza A, Arslan A, Atiq MU, Chan V, Patel RK. Unexpected outcome of daptomycin-induced eosinophilic pneumonia: rarity within a rarity. Cureus. 2019;11(12):e6271.
84.
Kumar S, Acosta-Sanchez I, Rajagopalan N. Daptomycin-induced acute eosinophilic pneumonia. Cureus. 2018;10(6):e2899.
85.
Basnet S, Tachamo N, Dhital R, Tharu B. Daptomycin associated eosinophilic pneumonia: case report and differential diagnoses. J Community Hosp Intern Med Perspect. 2018;8(3):152–5.
86.
Abelenda Alonso G, Montes Rodríguez I, Martín Torres J, Del Valle Loarte P. Daptomycin eosinophilic pneumonia: an adverse effect to be aware of. Rev Esp Quimioter. 2018;31(3):282–4.
87.
Rachid M, Ahmad K, Saunders-Kurban M, Fatima A, Shah A, Nahhas A. Daptomycin-induced acute eosinophilic pneumonia: late onset and quick Recovery. Case Rep Pulmonol. 2017;2017:8525789.
88.
Raru Y, Zeid F, Browning S, Saunders E. Two patients with daptomycin induced eosinophilic pneumonia with different presentations and treatment. Respir Med Case Rep. 2018;23:29–32.
89.
Higashi Y, Nakamura S, Tsuji Y, Ogami C, Matsumoto K, Kawago K, et al. Daptomycin-induced eosinophilic pneumonia and a review of the published literature. Intern Med. 2018;57(2):253–8.
90.
Nickerson M, Bhargava A, Kale-Pradhan P. Daptomycin-associated eosinophilic pneumonia with rechallenge: a case report. Int J Clin Pharmacol Ther. 2017;55(6):521–4.
91.
Hirai J, Hagihara M, Haranaga S, Kinjo T, Hashioka H, Kato H, et al. Eosinophilic pneumonia caused by daptomycin: six cases from two institutions and a review of the literature. J Infect Chemother. 2017;23(4):245–9.
92.
Zaccarini CG, Dong X. Poster 53 daptomycin-induced acute eosinophilic pneumonia in a patient receiving rehabilitation post prosthetic joint infection: a case report. PM R. 2016;8(9S):S178.
93.
Hatipoglu M, Memis A, Turhan V, Mutluoglu M, Canoglu K. Possible daptomycin-induced acute eosinophilic pneumonia in a patient with diabetic foot infection. Int J Antimicrob Agents. 2016;47(5):414–5.
94.
Montenegro O, Del Campo R, Del Rio JJ, Ambrós Checa A. Neumonía eosinofílica aguda secundaria a daptomicina. Enferm Infecc Microbiol Clin. 2016;34(6):390–1.
95.
Hagiya H, Hasegawa K, Asano K, Terasaka T, Kimura K, Nada T, et al. Myopathy and eosinophilic pneumonia coincidentally induced by treatment with daptomycin. Intern Med. 2015;54(5):525–9.
96.
Patel JJ, Antony A, Herrera M, Lipchik RJ. Daptomycin-induced acute eosinophilic pneumonia. Wis Med J. 2014;113(5):199–201.
97.
Yusuf E, Perrottet N, Orasch C, Borens O, Trampuz A. Daptomycin-associated eosinophilic pneumonia in two patients with prosthetic joint infection. Surg Infect. 2014;15(6):834–7.
98.
Corona Pérez-Cardona PS, Barro Ojeda V, Rodriguez Pardo D, Pigrau Serrallach C, Guerra Farfán E, Amat Mateu C, et al. Clinical experience with daptomycin for the treatment of patients with knee and hip periprosthetic joint infections. J Antimicrob Chemother. 2012;67(7):1749–54.
99.
Rether C, Conen A, Grossenbacher M, Albrich WC. A rare cause of pulmonary infiltrates one should Be aware of: a case of daptomycin-induced acute eosinophilic pneumonia. Infection. 2011;39(6):583–5.
100.
Kalogeropoulos AS, Tsiodras S, Loverdos D, Fanourgiakis P, Skoutelis A. Eosinophilic pneumonia associated with daptomycin: a case report and a review of the literature. J Med Case Rep. 2011;5:13.
101.
Søndergaard TS, Schumacher H, Norup K. [Possible daptomycin-induced organizing pneumonia]. Ugeskr Laeger. 2010;172(32):2172–4.
102.
Miller BA, Gray A, LeBlanc TW, Sexton DJ, Martin AR, Slama TG. Acute eosinophilic pneumonia secondary to daptomycin: a report of three cases. Clin Infect Dis. 2010;50(11):e63–8.
103.
Eckhardt LGJ, Kelley JL, Maes D. Challenges in managing a multifactorial eosinophilic pneumonia: daptomycin vs strongyloidiasis case report. BMC Infect Dis. 2022;22(1):873.
104.
Patel A, Ramakrishna S, Shuman M, Yadukumar L, Sheikh AAE, Mohfouz A. Daptomycin-induced eosinophilic pneumonitis: early recognition and empiric steroid therapy. Chest. 2022;161(6):A259.
105.
Zimmer MA, Haffner E, Weisser CW, Mols G. Daptomycin-induzierte eosinophile Pneumonitis im Rahmen eines Endoprothesenfrühinfektes. Anaesthesist. 2020;69(6):414–20.
106.
Allen JN. Drug-induced eosinophilic lung disease. Clin Chest Med. 2004;25(1):77–88.
107.
Nickerson M, Bhargava A, Kale-Pradhan PB. Daptomycin-associated eosinophilic pneumonia with rechallenge: a case report. Int J Clin Pharmacol Ther. 2017;55(6):521–4.
108.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug Reactions. Clin Pharmacol Ther. 1981;30(2):239–45.