The Characteristics of Antibiotic Use and Changing Patterns in an Intensive Care Unit/Yogun Bakim Ünitesinde Antibiyotik Kullanim ve Degisim Özellikleri

Headnote

Abstract

Objective: Infections are frequently seen in critically-ill patients and they are associated with increased mortality, morbidity and cost. Antibiotics play a very important role in the prevention and treatment of infections, yet associated with increased resistance especially when used inappropriately. In our study, we analyzed the data regarding antibiotic use before and during intensive care and we evaluated factors related to antibiotic change.

Material and Methods: The study was conducted in a medical intensive care unit (ICU) of a university hospital. Adult patients, who were admitted to the ICU and were using antibiotics in a 1 year-period, were included in the retrospective analysis.

Results: One hundred and seventy-six patients were included in the study. 58% of patients (n=103) were male. Mean (± standard deviation) age was 60.9±18.0 years. The percentage of patients who were referred to ICU from emergency room was 73%, while 23% of the patients were referred from inpatient services and 4% of the patients from another hospital. In 83% (n=146) of the patients, antibiotics were started before ICU admission. The primary reason for initiation of antibiotic therapy was recorded as pneumonia in 57% of the patients. Antibiotics were changed in 39% (n=69) of patients upon admission to ICU and in 68% (n=120) of patients during ICU stay. The sequential organ failure assessment (SOFA) score on the day of antibiotic change was higher than the SOFA score on ICU admission (p=0.001).

Conclusion: Antibiotic change is highly made in critically ill patients. Mostly patients use antibiotic before ICU admission. SOFA score can be used for antibiotic change decision.

Keywords: Critically ill, infection, antibiotic, intensive care unit

Received: 02.05.2016 Accepted: 09.09.2016

Ethics Committee Approval: Ethics committee approval was received for this study from the ethics committee of Hacettepe University School of Medicine.

Informed Consent: Patient inform consent was not obtained due to the retrospective observational study.

Peer-review: Externally peer-reviewed.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

Öz

Amaç: infeksiyonlar yogun bakim (YBÜ) hastalarinda siklikla görülür ve artmig mortalite morbidite ve maliyetle iligkilidir. Antibiyotikler infeksiyonlarin tedavisi ve önlenmesinde önemli rol almalarina ragmen özellikle uygunsuz kullanimda direnç artimi ile iligkilendirilirler. Bu çaligmada, yogun bakim öncesi ve esnasinda antibiyotik kullanimini analiz ettik ve antibiyotik degigimi ile ilgili faktörleri degerlendirdik.

Gereç ve Yöntemler: Çaligma bir üniversite hastanesi erigkin medikal yogun bakim ünitesinde yapildi. Çaligmaya 1 yillik periyotta yogun bakima yatan ve antibiyotik kullanan erigkinler dahil edildi ve retrospektif olarak analiz edildi.

Bulgular: Çaligmaya 176 hasta dahil edildi. Hastalarin %58'i (n=103) erkekti. Ortalama (± standart sapma) yag 60,9±18,0 idi. YBÜ'ye alinan hastalarin %72,7'si acil servisten gelirken %23,3'ü yatan hasta servislerinden ve %4'ü bagka bir hastaneden gelmigti. Hastalarin %83'üne (n=146) yogun bakim öncesi antibiyotik baglanmigti. Antibiyotik baglanmasinin birincil nedeni %56,8 ile pnömoniydi. YBÜ geligte %39,2 (n=69) oraninda ve YBÜ yatigi esnasinda %68,2 (n=120) oraninda antibiyotik degigtirilmigti. Antibiyotik degigim günü Sequential Organ Failure Assessment skoru (SOFA) YBÜ yatig günü SOFA skorundan yüksekti (p=0,001).

Sonuç: Yogun Bakim hastalarinda yüksek oranda antibiyotik degigimi yapilmaktadir. Hastalarin çogu yogun bakim öncesi antibiyotik kullanmaktadir. Antibiyotik degigim kararinda SOFA skoru degerlendirilebilir.

Anahtar Kelimeler: Kritik hasta, enfeksiyon, antibiyotik, yogun bakim ünitesi

Gelig Tarihi: 02.05.2016 Kabul Tarihi: 09.09.2016

Etik Komite Onayi: Bu çaligma için etik komite onayi Hacettepe Üniversitesi Tip Fakültesi'nden alinmigtir.

Hasta Onami: Gözlemsel retrospektif çaligma oldugu için hasta onamina gerek yoktur.

Hakem Degerlendirmesi: Dis bagimsiz.

Çikar Çatismasi: Yazarlar çikar çatigmasi bildirmemiglerdir.

Finansal Destek: Yazarlar bu çaligma için finansal destek almadiklarini beyan etmiglerdir.

Introduction

Infections are frequent problems in critically-ill patients and they are associated with increased mortality, morbidity and cost (1-4). Compared to the other hospitalized patients, presence of concomitant co-morbidities, severe acute physiological disorders, relative immunosuppression and frequent invasive procedures are the most common risk factors for acquisition of infections in the critically-ill patients who generally receive longer and various kinds of antibiotics (5, 6). These factors lead to emergence of multi-drug-resistant microorganisms in intensive care units (ICU) (7, 8) and since treatment of resistant microorganisms is difficult, this problem results in increased mortality, morbidity and costs (9, 10).

Development of resistance is related with antibiotic use. Therefore, antibiotic prescription strategies before and during ICU stay are crucial. In this study, we investigated the frequency of antibiotic use before ICU admission, the frequency of antibiotic changes, and we evaluated the factors related to antibiotic change.

Material and Methods

The study was conducted in Medical Intensive Care Unit of a university hospital. Adult patients, who were admitted to ICU between January 1st, 2013 and January 1st, 2014, who stayed for more than 48 hours and were using antibiotics, were included in the study. Data were collected retrospectively from the patient files and hospital database.

Age, gender, Acute Physiology and Chronic Health Evaluation Score (APACHE II), Sequential Organ Failure Assessment (SOFA) score, Creactive protein (CRP) and procalcitonin (PCT) values, place before ICU admission, the primary reason for the antibiotic initiation, place where the first culture was taken, duration of hospitalization and antibiotic use before ICU admission, the number and reason of antibiotic changes during ICU stay, , isolated microorganisms, sites of infection, total duration of antibiotic use and duration of hospitalization were recorded.

Ethical committee approval was obtained prior to the study (GO 14/191-29, 19.03.2014)

Statistical analysis

Analysis was performed using SPSS version 21.0.0.1 (SPSS, IBM, Armonk, NY, USA). The descriptive statistical method was used for demographic data. Wilcoxon test was used for the analysis of ordered variables. Pearson correlation test was used to assess the correlation between numerical variables. Results are presented as mean ± standard deviation or median (minimum-maximum). A p value <0.05 was considered as statistically significant.

Results

A total of 176 patients were included in the study. The mean ± standard deviation (SD) age of patients was 60.9±18.0 years. The number of male patients was 103 (58%). The descriptive and demographic information of patients are shown in Table 1. The patients were mostly transferred to ICU from emergency department (73%). Acute respiratory failure was the first reason for ICU admission (67%) (Table 1).

Antibiotics were started prior to ICU admission in 83% (n=146) of the patients. The median (minimum-maximum) duration of antibiotic use before ICU was 2 (0-59) days. Total duration of antibiotic use was 17.5 (1116) days. The most common reason for antibiotic initiation was pneumonia (57%). Cultures were taken from at least one site in 75% patients prior to antibiotic treatment (Table 2). As shown in Table 2, in 39% of the patients, antibiotics were changed at ICU admission. The most common isolated microorganism was Acinetobacter baumannii (24%). The most common infection site was respiratory system (35%) and quantitative deep tracheal aspirate was the most frequent (35%) culture method.

SOFA score was higher on antibiotic change day compared to the score calculated on ICU admission day (p=0.001, Table 3). The relationships between SOFA, CRP and Procalcitonin values in ICU admission day and antibiotic change day are shown in Table 4. There was weak, yet significant, correlation between SOFA-CRP SOFA-Procalcitonin and CRP-Procalcitonin values (Table 4).

The median lengths of ICU and hospital stay were 9.5 (1-72) and 23 (5184), respectively. ICU mortality was 31.8% and hospital mortality was 42.6%.

Discussion

In this study, we evaluated the antibiotic use in ICU. We showed that the vast majority of critically ill patients were exposed to antibiotics before ICU admission. Antibiotics were changed at ICU admission in significant number of patients. In addition, we found that SOFA score was higher on antibiotic change day.

One of the major causes of increased resistance is antibiotic use prior to intensive care admission (11). In a prospective observational study in 41 French ICUs, Montravers et al. (12) found that 28% patients already were administered antibiotic therapy before ICU admission. In contrast, in our study, 83% of patients had already been using antibiotics before ICU admission. In our study, in 75% of patients, cultures were obtained prior to antibiotic therapy. However, we have inadequate data about the adequacy and appropriateness of culture sites since in majority of patients only blood cultures were taken.

Extended Prevalence and Epidemiology of Infection in Critically-ill (EPIC) study (13), in which the prevalence and outcome of ICU acquired infections were investigated, showed that the most common site of infection was lungs with a frequency of 64%, similar to our study where the most frequent site being lungs with a frequency of 67%. In the EPIC II study, the culture-positivity was 70% similar to our study in which frequency of positive cultures was 66%. The most common isolated microorganism in our study was Acinetobacter baumannii with a frequency of 23.8%. In the EPIC II study, prevalence of Acinetobacter infection differed widely according to geographical regions. It was found to be 3.7% in North America where as 20% in Asia with an average prevalence rate of 9% (13).

In our study, antibiotic changing rate is 39% probably because of better evaluation of patients in the ICU and because critically-ill patients might have more complicated infections with different antibiotic susceptibility profiles. Nevertheless, using different antibiotics can cause more resistant infections (11).

SOFA score is developed to evaluate the degree and severity of organ failures, generally used to track a patient's status during the stay in ICU (14-16). Several studies have shown that SOFA score can be used to predict short- and long-term mortality (14, 17, 18). In our study, we found that there was a statistically significant difference between the SOFA score on ICU admission day and the score on the day when antibiotic was changed. Therefore, an increase in SOFA score might be a warning sign for acquisition of new infection or new microorganism with a different antibiotic susceptibility profile.

The markers such as CRP and PCT are used as surrogate markers in diagnosis and follow-up of infections. Several studies revealed that PCT had greater diagnostic accuracy than CRP IL-6, IL-8 to distinguish between bacterial sepsis and non-infectious etiologies of systemic inflammatory response syndrome (SIRS) (19-21). In contrast, some other studies have shown greater utility of CRP than PCT (22, 23). The debate of biomarker guided antibiotic therapy is ongoing. Two-center randomized controlled trial demonstrated that measuring daily PCT and using PCT guidance for antibiotic initiation and withholding resulted in a decrease in overall antibiotic use from 15 to 10 days in 101 patients with ventilator associated pneumonia (VAP) (24). In a French study (25) on non-surgical patients with suspected bacterial infection (73% with a respiratory infection) in seven ICUs, PCT-guided treatment initiation and discontinuation provided 23% more antibiotic free days compared to the control group (25). On the other hand, in a RCT in two Brazilian ICUs, a CRP-based algorithm was compared to a PCT-based algorithm in patients with severe sepsis and septic shock and CRP-based algorithm was found to have similar success (26). In our study, we observed that there is a moderate correlation between PCT versus SOFA and CRP versus SOFA at the antibiotic change day. Unfortunately, PCT and CRP had not been performed in all patients.

Antibiotic duration is another factor related with development of resistance. Therefore, antibiotic duration has been progressively shortened for many infectious syndromes (27). Current recommendations for duration of antibiotics for community-acquired pneumonia are about 7 days (28), for pyelonephritis 5-7 days (29) and VAP 8 days (30). In our study, median antibiotic use before ICU admission was 2 days (min-max 0-59) and the overall median antibiotic use during intensive care stay was as long as 17 days (2-116). Reasons for using antibiotics for a long duration are as follows: First, there is not a formal antibiotic stewardship program in our hospital. Increased resistance rates mandate that all ICUs should incorporate an antibiotic stewardship program with a multidisciplinary approach to decrease resistance and improve outcome (31). Secondly, using more antibiotics before ICU admission leads to acquisition of more resistant microorganisms, which leads to longer treatment duration. Third, we do not have a formal algorithm for antibiotic initiation, de-escalation or withholding. And the last but not the least, intensivists in Turkey have minimal roles in antibiotic prescriptions due to legal restraints, which need to be reviewed.

Our study has some limitations. It is a retrospective study. Furthermore, we could not assess whether cultures were obtained from appropriate sites especially before ICU admission. We were not be able to present information about timing and appropriateness of empirical antibiotic treatment, as well. PCT and CRP measurements were not performed in antibiotic changing day, in all patients. Finally, we could not determine the exact causes of antibiotic changes.

Conclusion

Antibiotic consumption especially prior to ICU admission is very high in critically ill patients. SOFA score might be used as a warning score for decision of antibiotic change.

References

References

1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-10. [CrossRef]

2. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34(2):344-53. [CrossRef]

3. Harrison DA, Welch CA, Eddleston JM. The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database. Crit Care. 2006;10(2):R42. [CrossRef]

4. Esteban A, Frutos-Vivar F Ferguson ND, Penuelas O, Lorente JA, Gordo F et al. Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward. Crit Care Med. 2007;35(5):1284-9. [CrossRef]

5. Hynes-Gay P Lalla P Leo M, Merrill-Bell A, Nicholson M, Villaruel E. Understanding sepsis: from SIRS to septic shock. Dynamics. 2002;13(1):17-20, 2-4; quiz 5-6.

6. Kaye KS, Marchaim D, Smialowicz C, Bentley L. Suction regulators: a potential vector for hospital-acquired pathogens. Infect Control Hosp Epidemiol. 2010;31(7):772-4. [CrossRef]

7. National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1992-April 2000, issued June 2000. Am J Infect Control. 2000;28(6):429-48. [CrossRef]

8. Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, et al. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol. 2008;29(11):996-1011. [CrossRef]

9. Schwaber MJ, Carmeli Y The effect of antimicrobial resistance on patient outcomes: importance of proper evaluation of appropriate therapy. Crit Care. 2009;13(1):106. [CrossRef]

10. Giske CG, Monnet DL, Cars O, Carmeli Y, ReAct-Action on Antibiotic R. Clinical and economic impact of common multidrug-resistant gram-negative bacilli. Antimicrob Agents Chemother. 2008;52(3):813-21. [CrossRef]

11. Marchaim D, Chopra T, Bhargava A, Bogan C, Dhar S, Hayakawa K, et al. Recent exposure to antimicrobials and carbapenem-resistant Enterobacteriaceae: the role of antimicrobial stewardship. Infect Control Hosp Epidemiol. 2012;33(8):817-30. [CrossRef]

12. Montravers P Dupont H, Gauzit R, Veber B, Bedos JP Lepape A, et al. Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units. Crit Care. 2011;15(1):R17. [CrossRef]

13. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323-9. [CrossRef]

14. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707-10. [CrossRef]

15. Vincent JL, de Mendonca A, Cantraine F Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800. [CrossRef]

16. Cabre L, Mancebo J, Solsona JF Saura P Gich I, Blanch L, et al. Multicenter study of the multiple organ dysfunction syndrome in intensive care units: the usefulness of Sequential Organ Failure Assessment scores in decision making. Intensive Care Med. 2005;31(7):927-33. [CrossRef]

17. Ferreira FL, Bota DP Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286(14):1754-8. [CrossRef]

18. Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F Thijs L, et al. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med. 1999;25(7):68696. [CrossRef]

19. Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164(3):396-402. [CrossRef]

20. Muller B, Becker KL, Schachinger H, Rickenbacher PR, Huber PR, Zimmerli W, et al. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med. 2000;28(4):977-83. [CrossRef]

21. Simon L, Gauvin F Amre DK, Saint-Louis P Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39(2):206-17. [CrossRef]

22. Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, et al. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care. 2007;11(2):R38. [CrossRef]

23. Ingram PR, Inglis T, Moxon D, Speers D. Procalcitonin and C-reactive protein in severe 2009 H1N1 influenza infection. Intensive Care Med. 2010;36(3):52832. [CrossRef]

24. Stolz D, Smyrnios N, Eggimann P Pargger H, Thakkar N, Siegemund M, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J. 2009;34(6):1364-75. [CrossRef]

25. Bouadma L, Luyt CE, Tubach F Cracco C, Alvarez A, Schwebel C, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010;375(9713):463-74. [CrossRef]

26. Oliveira CF Botoni FA, Oliveira CR, Silva CB, Pereira HA, Serufo JC, et al. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med. 2013;41(10):2336-43. [CrossRef]

27. Hayashi Y, Paterson DL. Strategies for reduction in duration of antibiotic use in hospitalized patients. Clin Infect Dis. 2011;52(10):1232-40. [CrossRef]

28. Woodhead M, Blasi F Ewig S, Garau J, Huchon G, Ieven M, et al. Guidelines for the management of adult lower respiratory tract infections-full version. Clin Microbiol Infect. 2011;17 Suppl 6:E1-59. [CrossRef]

29. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-20. [CrossRef]

30. Chastre J, Wolff M, Fagon JY, Chevret S, Thomas FWermert D, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588-98. [CrossRef]

31. Bassetti M, De Waele JJ, Eggimann P Garnacho-Montero J, Kahlmeter G, Menichetti F et al. Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Intensive Care Med. 2015;41(5):776-95. [CrossRef]