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Letters to the Editor
Antimicrobial resistance is a risk factor for mortality
in adults with sickle cell disease
Sickle cell disease (SCD), an inherited red blood cell disorder caused by homozygous or compound heterozy- gous inheritance of mutations in the b-globin gene, affects 1 in 365 African Americans.1 SCD is considered an immunodeficient state2 and infectious complications are a major contributor to the morbidity and mortality.3 Newborn screening, penicillin prophylaxis, and pneumo- coccal vaccination have led to reductions in sepsis-related mortality and > 95% of children with SCD living in high- resource settings now survive into adulthood.4 Despite these measures, high rates of hospitalizations in SCD patients are characterized by fevers5 and 14–18% of deaths are attributed to infectious causes in contempo- rary SCD cohorts.3
Antimicrobial-resistant infections are a global public health crisis associated with high rates of morbidity, health-related costs, and death in the general population.6 Penicillin prophylaxis may be leading to changes in antimicrobial resistance patterns in SCD. In a cohort of SCD children, 71% of whom were receiving penicillin prophylaxis, nasopharyngeal carriage of penicillin-resis- tant Streptococcus pneumoniae was observed in 55% of iso- lates.7 Antimicrobial resistance patterns in SCD adults are less clear and their impact on survival are not well under- stood.
We conducted a longitudinal study to i) identify risk factors for multidrug resistant (MDR) infections in adults with SCD, ii) compare antimicrobial resistance patterns to 16,000 propensity score-matched African Americans,
and iii) determine the association of MDR infections on survival in SCD adults enrolled in a prospective registry at the University of Illinois at Chicago (UIC).
We analyzed 320 SCD patients receiving medical care at UIC Hospital between January 1, 2017 and April 14, 2020. The protocol was approved by the Institutional Review Board and all subjects provided written informed consent.
Baseline demographic, clinical, and laboratory vari- ables were obtained at each patient’s first outpatient visit during the study period from the Cerner Medical Systems. Central venous catheterizations and diabetes diagnosis were queried using pertinent 9th and 10th Procedure Coding system editions of the International Classification of Disease (ICD-9-PCS and ICD-10-PCS) during the study period (Online Supplementary Table S1). Pneumococcal conjugate vaccine (PCV13) and pneumo- coccal polysaccharide vaccine (PPSV23) administration were queried during the 5 years prior to and including the study period. A blood culture contaminant was defined as a blood culture isolating coagulase-negative Staphylococcus, Bacillus species, Corynebacterium species, Propionibacterium species, or Streptococcus viridans group in less than 50% of simultaneously ordered cultures or in only one positive culture result.8 Organisms were consid- ered to be multidrug resistant if the isolate organism was non-susceptible to three or more categories of antibiotics according to the European Center for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) guidelines.9
Between January 1, 2017 and April 14, 2020, 34,612 adults with culture data and race classified as “black” or
Table 1. Clinical and laboratory values stratified by infection status in patients with sickle cell disease.
n
Age at first encounter (years) 299
Male (%) / Female (%) 299 HbSS/SB0-thalassemia genotype 299 Hydroxyurea use (%) 299 Diabetes diagnosis (%) 299 Leg ulcer diagnosis (%) 295 Avascular necrosis diagnosis (%) 295 Pneumococcal vaccinations (%)*
13-valent 299
23-valent
No or non-MDR Infection
37(29-48)
124 (41%) / 175 (59%) 225 (75%)
130 (43%)
23 (8%)
35 (12%)
93 (32%)
189 (63%)
179 (60%)
124 (113 - 135)
9.4 (7.0 - 12.3)
9.3 (8.1 - 10.6)
5.8 (2.2 - 11.0)
295 (207 - 374)
174 (120 - 271)
305 (230 - 405)
339 (89 - 1076)
124 (95 - 141)
64 (21%)
2(0-4)
213 (71%)
6 (3%)
n MDR Infection P 21 36 (31 - 50) 0.8
21 3 (14%) / 18 (86%)
21 18 (86%) 0.3 21 9 (43%) 0.9 21 3 (14%) 0.3 21 1 (5%) 0.3 21 10 (48%) 0.1
21 15 (71%) 0.4
0.014
Systolic blood pressure (mmHg) 274
White blood cell count (x103/mL) 260
7 (33%)
20 120 (112 - 131) 0.4
18 11.2 (9.1 - 12.4) 0.1 18 9.0 (8.4 - 9.4) 0.5 15 2.3 (1.9 - 4.2) 0.05 18 400 (244 - 439) 0.1 16 234 (156 - 354) 0.07 13 333 (287 - 428) 0.3 12 839 (332 - 2779) 0.08 17 106 (55 - 141) 0.6
0.017
Hemoglobin (g/dL) 260
Hemoglobin F (%) 165
Platelet count (x103/mL) 260
Reticulocyte count (x103/mL) 250
Lactate dehydrogenase (u/L) 184
Ferritin (ng/mL) 182
eGFR (ml/min/1.73 m2) 253
Central venous catheters (n) 299
Vaso-occlusive crises (n/year) 299
Acute chest syndrome history (%) 299
Heart failure (%) 186
21 10 (48%)
0.006
21 3(1-6) 0.1
21 18 (86%) 0.2
13 0 (0%) 0.5
Heart failure was defined as an ejection fraction < 50%: *The prevalence of pneumococcal vaccinations was assessed within the last 5 years of the study period. P<0.003 was considered statistically significant after the Bonferroni correction. MDR: multi-drug resistant; eGFR: estimated glomerular filtration rate.
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