The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics and Outcomes
2.2. Etiology and Antibiotic Resistance
2.3. Risk Factors for Gram-Negative Infection
2.4. Antibiotic Therapy
2.5. Risk Factors for Mortality
3. Materials and Methods
3.1. Setting, Patients and Study Design
3.2. Definitions
- SSTIs were defined as complicated (cSSTIs) if deep subcutaneous tissues were involved and/or surgery was necessary in addition to antimicrobial therapy [14].
- Necrotizing fasciitis was defined when the infection involved the superficial fascia, the subcutaneous tissue planes and underlying muscles [2].
- Co-morbidities were defined as the presence of one or more of the following conditions: chronic obstructive pulmonary disease, diabetes mellitus, chronic heart disease, chronic kidney disease (eGFR < 60 mL/min), chronic liver disease and cerebrovascular disease.
- Neutropenia was defined as an absolute neutrophil count ≤500 cells/μL.
- Bloodstream infection (BSI) was classified as nosocomial-acquired, healthcare-related, or community-acquired in accordance with previously reported criteria [15].
- Previous corticosteroid treatment was defined as the administration of 20 mg of prednisone, or equivalent dosing, for at least four weeks within the last 30 days from BSI onset.
- Septic shock was defined as a systolic blood pressure <90 mmHg that was unresponsive to fluid treatment and that required vasoactive drug therapy.
- GNB were considered multidrug-resistant (MDR) if any of the following were present: (1) extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, (2) AmpC cephalosporinase hyperproducing Enterobacterales, (3) carbapenem-resistant Enterobacterales, (4) MDR strains of Pseudomonas aeruginosa and Acinetobacter baumannii, and (5) microorganisms with intrinsic resistance mechanisms (e.g., Stenotrophomonas maltophilia).
- MDR strains were defined based on previously described criteria [16].
- MDR Gram-positive organisms included methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Enterococcus faecium.
- Initial empirical antibiotic therapy was considered inadequate if the treatment regimen did not include at least one antibiotic active in vitro against the infecting microorganism.
- The early and overall case-fatality rates were defined as death from any cause within seven and 30 days of bacteremia onset, respectively.
3.3. Microbiology
3.3.1. Blood Sample Collection and Laboratory Equipment
3.3.2. Identification Methods
3.4. Statistical Evaluation
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | No.164 | Percentage (%) |
---|---|---|
Age (years, median, range) | 61 (19–91) | |
Female sex | 75 | 46 |
Solid tumor | 87 | 53 |
Breast | 16 | 18 |
Gynecological | 13 | 15 |
Colon | 10 | 11.5 |
Head and neck | 9 | 10 |
Prostate | 7 | 8 |
Urothelial | 7 | 8 |
Other | 25 | 29 |
Hematological malignancy | 77 | 47 |
Lymphoma | 28 | 36 |
Leukemia | 25 | 32 |
Other | 24 | 31 |
Hematopoietic stem cell transplant | 19 | 12 |
Comorbidities | 57 | 35 |
Diabetes mellitus | 26 | 16 |
Chronic heart disease | 11 | 7 |
Chronic obstructive pulmonary disease | 9 | 5.5 |
Chronic renal disease | 7 | 4 |
Chronic liver disease | 6 | 4 |
Primary location SSTI a (n = 153) | ||
Limbs | 91 | 59.5 |
Trunk | 33 | 21.5 |
Perianal-genital | 15 | 10 |
Head and neck | 14 | 9 |
Local infection characteristics | ||
Erythema | 130 | 79 |
Pain | 115 | 70 |
Hot | 104 | 63 |
Swelling | 95 | 58 |
Suppuration | 66 | 40 |
Abscess | 27 | 16.5 |
Necrosis | 33 | 20 |
Necrotizing fasciitis | 7 | 4 |
Complicated SSTI a | 88 | 57 |
Imaging of affected area (n = 161) | 55 | |
Computed tomography scan | 36 | 22 |
Ultrasound | 13 | 8 |
Magnetic resonance | 6 | 4 |
Microbiological studies | ||
Culture | 57 | 36 |
Gram stain | 52 | 33 |
Site of acquisition | ||
Health-care | 82 | 50 |
Nosocomial | 44 | 27 |
Community | 38 | 23 |
Previous antibiotic therapy (1 month) | 65 | 40 |
Neutropenia (<500 neutrophil/µL) | 38 | 23 |
<100 neutrophil/µL | 16 | 10 |
Vascular catheter | 69 | 42 |
Corticosteroid therapy (1 month) | 63 | 38 |
Septic shock at onset | 21 | 13 |
Empirical antibiotic therapy (n = 155) | ||
β-lactam + β-lactam inhibitors | 77 | 50 |
Cephalosporins | 50 | 32 |
Carbapenems | 26 | 17 |
Aminoglycosides | 30 | 19 |
Glycopeptides | 29 | 19 |
Quinolones | 14 | 9 |
Aztreonam | 2 | 1 |
Daptomycin | 20 | 13 |
Combination therapy | 91 | 59 |
Need for drainage/surgery | 30 | 18 |
Intensive care unit admission | 12 | 7 |
48 h case-fatality rate | 10 | 6 |
7-day case-fatality rate | 20 | 12 |
30-day case-fatality rate | 35 | 21 |
Causative Organisms | No.180 a | Percentage (%) |
---|---|---|
Gram-positive bacteria | 89 | 49 |
Staphylococcus aureus | 40 | 45 |
Methicillin-resistant S. aureus | 8 | 9 |
Coagulase-negative staphylococci | 5 | 6 |
Streptococcus spp. | 33 | 37 |
S. agalactiae | 12 | 13 |
S. pyogenes | 10 | 11 |
S. pneumoniae | 2 | 2 |
S. equisimilis | 2 | 2 |
S. constellatus | 2 | 2 |
S. anginosus | 2 | 2 |
Other streptococcus b | 3 | 3 |
Enterococcus spp. | 7 | 8 |
Enterococcus faecalis | 4 | 4.5 |
Enterococcus faecium | 3 | 3 |
Corynebacterium spp. | 3 | 3 |
Propionibacterium acnes | 1 | 1 |
Gram-negative bacteria | 82 | 46 |
Pseudomonas aeruginosa | 31 | 38 |
Escherichia coli | 29 | 35 |
Klebsiella pneumoniae | 11 | 13 |
Enterobacter spp. | 3 | 4 |
Haemophilus influenzae | 1 | 1 |
Morganella morganii | 1 | 1 |
Serratia marcescens | 1 | 1 |
Stenotrophomonas maltophilia | 1 | 1 |
Achromobacter xylosoxidans | 1 | 1 |
Citrobacter spp. | 1 | 1 |
Aeromonas spp. | 1 | 1 |
Moraxella caprae | 1 | 1 |
Anaerobic bacteria | 7 | 4 |
Bacteroides spp. | 4 | |
Clostridium spp. | 2 | |
Actinomyces odontolyticus | 1 | |
Fungi | 2 | 1 |
Candida parapsilosis | 1 | |
Candida tropicalis | 1 | |
Polymicrobial infection | 12 | 7 |
Multidrug-resistant organisms | 26 | 14 |
Multidrug-resistant GNB c | 13 | 16 |
Characteristic | Gram-Positive (N = 77) No. (%) | Gram-Negative (N = 71) No. (%) | Univariate p-Value | Adjusted OR (95%CI) | Multivariate p-Value |
---|---|---|---|---|---|
Age, yr; median (range) | 64 (19–90) | 65 (25–91) | 0.875 | ||
Female sex | 34 (49) | 35 (51) | 0.53 | ||
Solid tumor | 42 (54) | 35 (45) | 0.52 | ||
Hematological malignancy | 35 (49) | 36 (51) | 0.52 | ||
Hematopoietic stem cell transplant | 8 (10) | 10 (14) | 0.49 | ||
Co-morbidities | 26 (34) | 23 (32) | 0.86 | ||
COPD a | 6(8) | 2(3) | 0.23 | ||
Diabetes mellitus | 12 (16) | 11 (15.5) | 0.98 | ||
Chronic kidney disease | 3 (4) | 4 (6) | 0.71 | ||
Chronic liver disease | 2 (3) | 4 (6) | 0.43 | ||
Chronic heart disease | 2 (3) | 7 (10) | 0.09 | ||
Previous antibiotic therapy | 25 (32.5) | 33 (47) | 0.07 | ||
Neutropenia (<500 neutrophil/µL) | 13 (17) | 18 (25) | 0.21 | ||
Vascular catheter | 27 (35) | 34 (48) | 0.11 | ||
Corticosteroid therapy (1 month) | 24 (31) | 33 (47) | 0.06 | 2.4 (1.2–5.1) | 0.015 |
Community-acquired infection | 15 (19.5) | 19 (27) | 0.29 | ||
Shock at presentation | 8 (10) | 11 (15.5) | 0.35 | ||
IEAT b | 15 (19.5) | 9 (13) | 0.26 | ||
Persistent bacteremia | 4 (5) | 2 (3) | 0.68 | ||
Characteristics of the lesion | |||||
Presence of skin necrosis | 10 (13) | 19 (27) | 0.03 | 2.4 (1.03–6) | 0.04 |
Purulent lesion | 28 (36) | 35 (49) | 0.11 | ||
Necrotizing fasciitis | 2 (3) | 3 (4) | 0.67 | ||
Site of infection | |||||
Trunk | 17 (23) | 13 (19) | 0.54 | ||
Limbs | 45 (62) | 40 (57) | 0.58 | ||
Head and neck | 7 (10) | 7 (10) | 0.93 | ||
Perianal-genital | 6 (8) | 9 (13) | 0.36 | ||
Outcome | |||||
Overall case-fatality rate (30 d) | 15 (19.5) | 18 (25) | 0.39 | ||
Early case-fatality rate (7 d) | 9 (12) | 10 (14) | 0.66 | ||
Very early case-fatality rate (48 h) | 4 (5) | 6 (8.5) | 0.43 |
Characteristic | Dead (N = 20) | Alive (N = 144) | Univariate p-Value | OR (95%CI) | Multivariate p-Value |
---|---|---|---|---|---|
Age, yr; median (range) | 69.5 (56–90) | 63 (19–91) | 0.04 | 1.07 (1.02–1.12) | 0.005 |
Female sex | 10 (50) | 65 (45) | 0.68 | 1.08 (0.32–3.63) | 0.89 |
Solid tumor | 13 (65) | 75 (52) | 0.28 | ||
Hematological malignancy | 7 (35) | 69 (48) | 0.28 | ||
Co-morbidities | 7 (35) | 50 (35) | 1.00 | ||
COPD a | 2 (10) | 7 (5) | 0.30 | ||
Diabetes mellitus | 1 (5) | 25 (17) | 0.20 | ||
Chronic kidney disease | 2 (10) | 5 (3.5) | 0.20 | ||
Chronic liver disease | 2 (10) | 5 (3.5) | 0.20 | ||
Chronic heart disease | 1 (5) | 10 (7) | 1.00 | ||
Gram-negative infection | 10 (50) | 61 (42) | 0.52 | ||
Infection due to MDR b organisms | 7 (35) | 19 (13) | 0.02 | 2.4 (0.66–8.84) | 0.18 |
Infection due to MDR-GNB c | 3 (15) | 10 (7) | 0.41 | ||
Neutropenia (<500 neutrophil/µL) | 2 (10) | 36 (25) | 0.17 | ||
Corticosteroid therapy (1 month) | 9 (45) | 54 (37.5) | 0.52 | ||
Shock at presentation | 9 (45) | 12 (8) | 0.00 | 14.8 (3.77–58.5) | 0.000 |
IEAT d | 7 (35) | 22 (15) | 0.05 | 5.01 (1.30–19.2) | 0.019 |
Presence of skin necrosis | 9 (45) | 26 (18) | 0.014 | 2.4 (0.71–8.3) | 0.15 |
Characteristic | Dead (N = 35) | Alive (N = 129) | Univariate p-Value | OR (95%CI) | Multivariate p-Value |
---|---|---|---|---|---|
Age, yr; median (range) | 66 (48–90) | 63 (19–61) | 0.014 | 1.03 (1.00–1.06) | 0.029 |
Female sex | 18 (51) | 57 (44) | 0.45 | 1.33 (0.56–3.18) | 0.51 |
Solid tumor | 22 (63) | 66 (51) | 0.19 | ||
Hematological malignancy | 13 (37) | 63 (49) | 0.19 | ||
Hematopoietic stem cell transplant | 2 (6) | 17 (13) | 0.37 | ||
Co-morbidities | 13 (37) | 44 (34) | 0.74 | ||
COPD a | 2 (6) | 7 (5) | 1.00 | ||
Diabetes mellitus | 3 (9) | 23 (18) | 0.18 | ||
Chronic kidney disease | 2 (6) | 5 (4) | 0.64 | ||
Chronic liver disease | 4 (11) | 3 (2) | 0.059 | ||
Chronic heart disease | 2 (6) | 9 (7) | 1.00 | ||
Community-acquired | 8 (23) | 29 (22.5) | 1.00 | ||
Etiology | |||||
Gram-positive | 15 (43) | 62 (48) | 0.58 | ||
Gram-negative | 18 (51) | 53 (41) | 0.27 | ||
Polymicrobial bacteremia | 3 (9) | 11 (8.5) | 1.00 | ||
Infection due to MDR b organisms | 11 (31) | 15 (12) | 0.004 | 2.78 (1.01–7.64) | 0.047 |
Infection due to MDR-GNB c | 5 (14) | 8 (6) | 0.15 | ||
Neutropenia (<500 neutrophil/µL) | 7 (20) | 31 (24) | 0.61 | ||
Corticosteroid therapy (1 month) | 19 (54) | 44 (34) | 0.03 | ||
Surgery/drainage | 5 (14) | 25 (19) | 0.62 | ||
Septic shock at presentation | 11 (31) | 10 (8) | 0.001 | 5.86 (1.97–17.4) | 0.001 |
IEAT d | 10 (29) | 19 (15) | 0.05 | 2.76 (0.99–7.69) | 0.051 |
Persistent bacteremia | 1 (3) | 6 (5) | 1.00 | ||
Intensive care unit admission | 5 (14) | 7 (6) | 0.14 | ||
Characteristic of the lesion | |||||
Presence of skin necrosis | 13 (37) | 22 (17) | 0.01 | 1.89 (0.71–5.04) | 0.199 |
Purulent lesion | 16 (46) | 55 (43) | 0.74 | ||
Necrotizing fasciitis | 3 (9) | 4 (3) | 0.168 |
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Castelli, V.; Sastre-Escolà, E.; Puerta-Alcalde, P.; Huete-Álava, L.; Laporte-Amargós, J.; Bergas, A.; Chumbita, M.; Marín, M.; Domingo-Domenech, E.; Badia-Tejero, A.M.; et al. The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients. Antibiotics 2023, 12, 1722. https://doi.org/10.3390/antibiotics12121722
Castelli V, Sastre-Escolà E, Puerta-Alcalde P, Huete-Álava L, Laporte-Amargós J, Bergas A, Chumbita M, Marín M, Domingo-Domenech E, Badia-Tejero AM, et al. The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients. Antibiotics. 2023; 12(12):1722. https://doi.org/10.3390/antibiotics12121722
Chicago/Turabian StyleCastelli, Valeria, Enric Sastre-Escolà, Pedro Puerta-Alcalde, Leyre Huete-Álava, Júlia Laporte-Amargós, Alba Bergas, Mariana Chumbita, Mar Marín, Eva Domingo-Domenech, Ana María Badia-Tejero, and et al. 2023. "The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients" Antibiotics 12, no. 12: 1722. https://doi.org/10.3390/antibiotics12121722