Underlying characteristics of patients harboring highly resistant Acinetobacter baumannii

Underlying characteristics of patients harboring highly resistant Acinetobacter baumannii

Underlying characteristics of patients harboring highly resistant Acinetobacter baumannii Siham Mahgoub, MDa Jimmie Ahmed, RNb Aaron E. Glatt, MDa,b,c...

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Underlying characteristics of patients harboring highly resistant Acinetobacter baumannii Siham Mahgoub, MDa Jimmie Ahmed, RNb Aaron E. Glatt, MDa,b,c Jamaica, New York Background: Highly resistant (HR) Acinetobacter baumannii (AB) are frequently hospital-acquired and may be important causes of severe nosocomial infections. Objective: Determine risk factors associated with such colonization/infection. Method: Retrospective review in 2000 of all AB isolates from sterile (blood, cerebrospinal fluid [CSF]) and nonsterile (respiratory, urine, and miscellaneous) sites. HR was defined as resistance to amikacin and/or imipenem and/or ampicillin-sulbactam. Isolates were analyzed as representing infection or colonization. A database including prior hospitalization, prior antibiotic use, nursing home residency, and procedures undergone was compiled. Results: One hundred twenty-two cases of AB were identified. Eighty-four met the definition of HR; 6 (4.9%) were completely resistant to all antibiotics. Four (4.7%) isolates were from sterile body sites (3 blood, 1 CSF); 43 (51.2%) were from respiratory sites; 20 (23.8%) were from urinary sites; and 17 (20.2%) were from “other” sites. Only 4 (20%) of the urinary, 6 (35.2%) of the miscellaneous, and 23 (53.4%) of the respiratory isolates were deemed true pathogens; all blood/CSF isolates were considered pathogens. Associated risk factors included prior antibiotic usage (71%); prior hospitalization (24%); prior nursing home residency (34%); ventilator use (77%); tracheostomy placement (56%); and Foley catheterization (85%). Twenty-seven (63%) of 43 respiratory, 8 (40%) of 20 urinary, and 6 (35%) of 17 “other” body isolates were treated. Outcome was not statistically significant in treated versus untreated patients. All patients with CSF/blood isolates underwent successful microbiologic eradication with 50% survival. The overall mortality rate was 10%. Conclusion: Antibiotics, Foley catheters, and tracheostomy/ventilator usage were strongly associated with AB isolation. Prior hospitalization and nursing home residency were less common risk factors. Outcome was not different in treated versus untreated patients, indicating colonization is a marker of severe illness but is not necessarily causal. (Am J Infect Control 2002;30:386-90.)

Acinetobacter baumannii (AB) are aerobic, gramnegative organisms that appear coccobacillary when stationary, whereas they take on rod forms during growth.1 AB are an important common cause of nosocomial (especially intensive care unit [ICU]) infections, such as lower respiratory infec-

tions, urinary tract infections, and bacteremia. Guidelines have been promulgated by the Centers for Disease Control and Prevention (CDC) to control AB infection. Nevertheless, AB infections remain a significant problem, with high morbidity and mortality and lengthened hospital stays.2

From Division of Infectious Diseases,a and Department of Infection Control,b St. Vincent Catholic Medical Centers, Brooklyn Queens Region, and New York Medical College.c

Differentiation between colonization and infection is critical to obviate inappropriate antibiotic use. Treatment, when necessary, is often difficult because of increasing resistance.3 Indeed, in our institution, as well as at many others, highly resistant AB are prevalent.

Reprint requests: Aaron E. Glatt, MD, St. Vincent Catholic Medical Centers, Brooklyn Queens Region, 88-25 153 St, Suite 3-R, Jamaica, NY 11432. Copyright © 2002 by the Association for Professionals in Infection Control and Epidemiology, Inc. 0196-6553/2002/$35.00 + 0 17/46/122648 doi:10.1067/mic.2002.122648

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It is extremely important to be able to identify patients at the highest risk of acquisition of resistant AB and to rapidly initiate appropriate interven-

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Mahgoub, Ahmed, and Glatt

Table 1. Risk factors for AB isolation (all isolates) Risk factors

HRAB (n = 84)

Control (n = 20)*

Table 2. Risk factors for AB isolation: Respiratory isolates

P value Risk factors

Prior antibiotic usage Cardiovascular ICU stay NH residency Surgery Prior hospitalization Diabetes Malignancy Respiratory Steroids Neurology Trauma Mechanical ventilation Tracheotomy

60 49 41 29 37 20 18 12 12 8 8 6 47 37

9 12 5 4 8 3 8 2 4 3 6 0 6 6

.035 1 .079 .288 .806 .553 .094 1 .504 .439 .026 .593 .047 .317

HRAB, Highly resistant Acinetobacter baumanii. *Control group consisted of patients with 20 sensitive strains of Acinetobacter baumanii.

Prior antibiotic usage Cardiovascular ICU stay H residency Surgery Prior hospitalization Diabetes Malignancy Respiratory Steroids Neurology Trauma Mechanical ventilation Tracheotomy

HRAB (n = 43)

Control (n = 20)*

P value

33 27 27 14 15 12 10 6 9 6 3 3 39 31

4 6 2 2 4 1 3 2 2 3 3 0 5 5

< .001 .029 < .001 .068 .377 .047 .524 1 .478 1 .372 .545 < .001 .001

HRAB, Highly resistant Acinetobacter baumanii. *Control group consisted of patients with 20 sensitive strains of Acinetobacter baumanii.

tions, isolation, and treatment. Our study was instituted to determine the characteristics and risk factors associated with such AB colonization/infection.

Table 3. Risk factors for AB isolation: Urinary isolates

PATIENTS AND METHODS Setting

Prior antibiotic usage Cardiovascular ICU stay NH residency Surgery Prior hospitalization Diabetes Malignancy Respiratory Steroids Neurology Trauma Foley catheter

This study was conducted in 2 community teaching hospitals (Mary Immaculate Hospital and St John’s Hospital) in Queens, NY.

Study design Retrospective chart review of all patients with AB isolates identified through infection control and microbiology records for the year 2000 was undertaken. Microbiologic identification was confirmed with the Microscan system (Dade Behring, West Sacramento, Calif). Individual patients with multiple positive isolates were counted only once; however, isolates with different sensitivity patterns were analyzed separately. Patient demographics and associated risk factors included, but were not limited to, prior antibiotic usage, prior nursing home residency, hospital floor and location, underlying comorbidity, and sites of AB isolation. Patient treatment and outcome were analyzed via retrospective chart review by an infectious diseases subspecialist. Twenty patients were randomly selected as the control group, whose AB isolates were sensitive com-

Risk factors

HRAB (n = 20)

Control (n = 20)*

P value

15 10 6 6 9 3 6 2 1 1 3 2 17

2 3 1 2 2 0 2 1 0 0 1 0 1

< .001 .041 .091 .235 .031 .231 .235 1 1 1 .605 .487 < .001

HRAB, Highly resistant Acinetobacter baumanii. *Control group consisted of patients with 20 sensitive strains of Acinetobacter baumanii.

pared with those of the study group (Tables 1 through 5).

Definitions used in our study Prior antibiotic usage: Use of broad-spectrum antibiotics—quinolones, carbapenems, β-lactams, or aminoglycosides—within 4 weeks before AB isolation. Prior hospitalization: Any admission to any hospital within the past year.

Mahgoub, Ahmed, and Glatt

388 Vol. 30 No. 7 Table 4. Risk factors for AB isolation: Sterile isolates Risk factors

HRAB (n = 4)

Control (n = 20)*

Table 5. Risk factors for AB isolation: Miscellaneous isolates

P value Risk factors

Prior antibiotic usage Cardiovascular ICU stay NH residency Surgery Prior hospitalization Diabetes Malignancy Respiratory Steroids Neurology Trauma

4 1 3 1 1 0 0 1 1 0 0 0

2 2 1 0 0 2 1 0 1 0 1 0

.001 .437 .008 .167 .167 1 1 .167 .312 n/a 1 n/a

HRAB, Highly resistant Acinetobacter baumanii. *Control group consisted of patients with 20 sensitive strains of Acinetobacter baumanii.

Prior antibiotic usage Cardiovascular ICU stay NH residency Surgery Prior hospitalization Diabetes Malignancy Respiratory Steroids Neurology Trauma

HRAB (n = 17)

Control (n = 20)*

P value

15 11 1 8 12 5 4 3 1 1 2 1

1 1 1 0 2 0 2 0 1 0 1 0

< .001 < .001 1 .001 < .001 .014 .383 .088 1 .459 .584 .459

HRAB, Highly resistant Acinetobacter baumanii. *Control group consisted of patients with 20 sensitive strains of Acinetobacter baumanii.

Hospital location: Where patient had been (eg, ICU, post-intensive [PI] care unit, or critical care unit) and/or was located (eg, ICU, PI care unit, critical care unit or medical, surgical, or obstetrics/gynecology ward) at the time the isolate was recovered.

Infection: Patients with AB isolates who, upon retrospective chart review, had clinical, radiographic, laboratory, and/or outcome evidence of infection.

Comorbid conditions: Underlying disease(s) or condition(s) that might have contributed or increased the risk of acquisition of infection (eg, diabetes; cardiovascular, respiratory, and/or neurological disease; cancer, trauma).

Highly resistant AB: Isolates resistant to imipenem, amikacin, or ampicillin-sulbactam.

Nosocomial factors: Procedures and/or other factors that potentially contribute to infection or colonization (eg, mechanical ventilation, tracheotomy, surgery, and Foley catheterization). (Note that all patients were presumed to have had various types of intravenous catheters, and because of the retrospective nature of this study and documentation concerns, no attempt was made to distinguish between types/location/duration of intravenous catheters.) Site(s) of AB isolates: Isolates were identified by the ordering physician as coming from blood, respiratory sites (sputum, tracheotomy, bronchoscopy, or bronchial wash specimen), urine, or wound or intravenous catheter tip. Colonization: Patients who had AB isolates recovered and who, upon retrospective chart review, had no clinical, radiographic, or other laboratory evidence of infection.

Completely resistant AB: Isolates resistant to all Federal Drug Administration approved antibiotics.

Statistical analysis Differences between groups were analyzed with use of the Fisher exact test (2–tailed). A P value of less than .05 was deemed statistically significant.

RESULTS All 122 charts (100%) of the 122 patients with AB isolates were reviewed. Sixty-two patients (50.8%) had a total of 84 different AB isolates that were highly/completely resistant. Tables 1-5 summarize the data based on risk factors that were statistically significant. Prior antibiotic usage was the most common risk factor for the acquisition of highly resistant AB when compared with a control group of 20 patients with more sensitive AB isolates. Sixteen of the 62 patients had multiple isolates (Table 6). These isolates had different resistant patterns and/or were from different sites. Six (4.9%) isolates (from 6 patients), which we described elsewhere,4 were completely resistant to all Federal Drug Administration approved antibiotics.

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Forty-two patients (34.4%) had 50 isolates resistant to imipenem. Nine patients (7.4%) had 10 isolates resistant to ampicillin-sulbactam. One patient (0.8%) had 1 isolate resistant to amikacin. Fifteen patients (12.3%) had 17 isolates resistant to both imipenem and ampicillin-sulbactam; 2 isolates (1.6%) were resistant to imipenem and amikacin. Four isolates (3.3%) were resistant to imipenem, amikacin, and ampicillin-sulbactam but remained initially sensitive to some other antibiotic. However, all eventually acquired a completely resistant AB.

Prior antibiotic use Quinolones were the most frequently administered antibiotic. Thirty-five (42%) of the patients received a quinolone before infection or colonization with AB. Four (4.7%) of the 84 isolates were from sterile sites (3 blood, 1 CSF). All were deemed true infections. Eighty isolates (95.2%) were from nonsterile sites: 43 of the 84 (51.2%) were respiratory; 20 (23.8%) were urinary; and 17 (20.2%) were from miscellaneous sites (mostly wounds [n = 12] and catheter tips [n = 5]).

Respiratory isolates Even though many of the patients had significant underlying risk factors and predisposing conditions to AB isolation, no statistical differences were evident between colonized versus infected patients.

Urinary isolates Of the 20 urinary isolates, only 4 (20%) were deemed to represent true infections; 16 (80%) represented colonization. No statistical significance was demonstrable between infected versus colonized patients.

Miscellaneous/sterile sites of AB isolation Of the 17 isolates in the miscellaneous group, 6 (35.2%) were deemed true infections and 11 (64.7%) were colonization. No statistical significance was demonstrable between infected versus colonized patients. Table 1 summarizes all the associated risk factors from all the different sites. Comparison between the study and control groups is shown in Tables 1 through 5.

Treatment and outcome Forty-five of the 84 isolates (53.6%) received treatment for highly/completely resistant AB infection (27 respi-

Table 6. Patients with multiple isolates Patient Patient Patient Patient Patient Patient Patient Patient Patient Patient Patient Patient Patient Patient Patient Patient

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Respiratory (2), urinary, blood Urinary, respiratory Blood, respiratory CSF, respiratory Respiratory (4), wound Wound,TLC, respiratory Respiratory,TLC Urinary, respiratory Urinary,TLC Blood,TLC Urinary, respiratory Respiratory (2) Respiratory,TLC Urinary (2) Urinary, respiratory Wound, urinary

ratory, 8 urinary, and 6 miscellaneous isolates and miscellaneous-site AB isolation). All 4 of the sterile body isolates were treated. Of some surprise was that clinical and microbiologic outcomes were not significantly different in treated versus untreated patients.

DISCUSSION Our study demonstrates that invasive procedures such as the usage of mechanical ventilators, tracheotomies, and Foley catheters are strongly associated with nosocomial acquisition of A baumannii, as also has been reported by others.3 Prior antibiotic usage (71.4%) was the most common risk factor for all of our 84 AB isolates. Cardiovascular risk factors (58.3%), ICU stay (49%), surgery (44%), nursing home residency (34.4%), prior hospitalization (24.0%), diabetes (21.0%), respiratory disorder (14.2%), malignancy (14.2%), neurological disorder and prior steroid use (9.5%), and trauma accounted for (7.1%). Our results demonstrated no statistical significance between infected versus colonized patients. Others have noted similar risk associations. Lortholary and colleagues3 have reported mechanical ventilation and urinary catheterization as associated risk factors; Okpara and Maswoswe5 demonstrated that mechanical ventilation, prior antibiotic usage, ICU stay, and surgery contributed to AB infection. Previous surgery was a major risk factor in another study.6 Our data agree with these findings. Baraibar et al7 reported that the comorbid conditions did not seem to be a significant factor in acquiring AB. However, our data support that cardiovascular, pulmonary, diabetes, and other comorbidities may very well have been additional factors leading to colonization or infection with AB. Our data concurred

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390 Vol. 30 No. 7 with that of Mulin and colleagues8 that urinary catheterization was strongly associated with AB urinary colonization. Foley catheters were present in 13 (81.2%) of 16 patients with AB urinary colonization.

been estimated as ranging from 23% to 71%.2 It is very difficult to compare mortality rates in different studies, however, without carefully controlling for the underlying patient differences.

Villers et al9 reported that prior quinolone usage led to endemic AB infection. Prior third-generation cephalosporin and aztreonam usage was associated with AB resistance in several Brooklyn hospitals.10 Emergence of AB β-lactams resistance is multifactorial; resistance is due to altered penicillin-binding proteins, decreased permeability of the outer membrane, and/or production of β-lactamases. In our study group, quinolones, followed by ceftazidime, were the most commonly used antibiotics before isolation of AB. Restriction policies have led to decreased AB isolation(s), and judicious antibiotic usage is certainly an important cornerstone in any effort to reduce resistance. In our study, high rates (55.5%) of imipenem resistance were present, as opposed to the findings of Husni et al,11 in which there was no imipenem resistance. Go et al12 attributed the emergence of imipenemresistant AB to the use of imipenem for the treatment of Klebsiella pneumoniae infections resistant to cephalosporins.

References

Risk factors and outcome were not different in infected versus colonized patients, suggesting that AB isolation is associated with severe debilitation and hospitalization but is not necessarily itself a more virulent pathogen than other nosocomial organisms. The overall mortality rate associated with colonization/infection with A baumannii in our study was 10%. AB-associated mortality in the ICU setting has

1. Allen DM, Hartman BJ. Acinetobacter species. Principles and practice of infectious diseases. Mandell GL, Bennett JE, Dolin R, editors. Churchill Livingstone; 2000. p. 2339-43. 2. Garcia-Garmendia JL, Ortiz-Leyba C, Garnacho-Montero J, et al. Mortality and the increased length of stay attributable to the acquisition of Acinetobacter in critically ill patients. Crit Care Med 1999;27(9):1794-8. 3. Lortholary O, Fagon JY, Hoi AB, et al. Nosocomial acquisition of mutiresistant Acinetobacter baumannii: risk factors and prognosis. Clin Infect Dis 1995;20:790-6. 4. Mahgoub S,Ahmed J, Glatt AE. Completely resistant Acinetobacter baumannii species. Infect Control Hosp Edidemiol 2002;23:477-9. 5. Okpara AU, Maswoswe JJ. Emergence of multidrug-resistant isolates of Acinetobacter baumannii.Am J Hosp Pharm 1994;51(21):2671-5. 6. Koeleman JG, Parlevliet GA, Dijkshoorn L, et al. Nosocomial outbreak of multi-resistant Acinetobacter baumannii on a surgical ward: epidemiology and risk factors for acquisition. J Hosp Infect 1997;37(2):113-23. 7. Baraibar J, Correa H, Mariscal D, et al. Risk factors for infection by Acinetobacter baumannii in intubated patients with nosocomial pneumonia. Chest 1997;112:1050-4. 8. Mulin B, Talon D, Viel JF, et al. Risk factors for nosocomial colonization with multiresistant Acinetobacter baumanni. Eur J Clin Microbiol Infect Dis 1995;14(7):569-76. 9. Villers D, Espaze E, Coste-Burel M, et al. Nosocomial Acinetobacter baumannii infections: microbiological and clinical epidemiology. Ann Intern Med 1998;129(3):182-9. 10. Manikal VM, Landman D, Saurina G, et al. Endemic carbapenemresistant species in Brooklyn, New York: citywide prevalence, interinstitutional spread, and relation to antibiotic usage. Clin Infect Dis 2000;31:101-6. 11. Husni RN, Goldstein LS, Arroliga AC, et al. Risk factors for an outbreak of multi-drug resistant Acinetobacter nosocomial pneumonia among intubated patients. Chest 1999;115:1378-82. 12. Go ES, Urban C, Burns J, et al. Clinical and molecular epidemiology of Acinetobacter infections sensitive only to polymyxin B and sulbactam. Lancet 1994:344:1329-32.

Correction In the article entitled, “Sharps Injury Recordkeeping Activities and Safety Produce Use in California Health Care Facilities: Pilot Study Results from the Sharps Injury Control Program” (Gillen M, Davis M, McNary J, Boyd A, Lewis J, Curran C, et al. Am J Infect Control 2002;30:269-76), the end of the first paragraph in the Methods section should have read: “The survey was conducted approximately 6 months after Cal/OSHA revised its bloodborne pathogens standard,3 which mandates the use of safety-enhanced devices, and approximately 6 months before all aspects of the California standard took effect.”