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Impact of Empirical Antibiotic Choice on the Clinical Outcomes of Patients Admitted to ICU with Sepsis and Septic Shock

Ihab B. Abdalrahman, Shaima N Elgenaid , Galal Mohamedani, Mohammed Elfatih Ahmed Yousif
American Journal of Educational Research. 2020, 8(9), 727-730. DOI: 10.12691/education-8-9-15
Received August 16, 2020; Revised September 19, 2020; Accepted September 28, 2020

Abstract

Introduction: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Sepsis is associated with high mortality rate. Early recognition and administration of appropriate empirical antibiotics therapy is associated with better outcomes; lower mortality rate and reduced length of stay. Objective: To assess the impact and appropriateness of empirical antibiotic choice on the clinical outcomes of sepsis and septic shock in intensive care department. Methods: The study included 53 patients admitted to Intensive Care Units. The type of empirical antibiotic was compared with the sensitivity profile of culture results. The clinical outcome was assessed as mortality or ICU discharges. Results: In this study, 58% of the patients were females and 50.9% were above 65 years. The most common risk factor for sepsis was recent hospitalization (32%) followed by diabetes mellitus (15%). The most common site of infection was the chest (34%). The majority of patients (81.1%) received combination empirical antibiotics. Patients who received appropriate empirical antibiotics had higher ICU discharge rates (P=0.001). Mortality rate was 67.9%; more than half of deaths (58%) occurred among patients with septic shock (P= 0.001). Conclusion: The use of appropriate empirical antibiotics in the management of sepsis and septic shock would result in better patient outcomes.

1. Introduction

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is defined as a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to substantially increase mortality 1. Over the past four decades, the incidence of sepsis has substantially increased, the latest estimates in the United States, Europe and the United Kingdom range between 0.4/1000 and 1/1000 of the population 2, 3, 4, 5, 6. Dagher et.al, reported the state of sepsis in the developing world between January 2008 and June 2012, they found that sepsis related deaths were around 40 % 7. In Saudi Arabia they reported high majority in septic shock 8.

Hospital mortality for patients diagnosed with sepsis in the developed countries has decreased from 28% to 18% 3. This big difference is related to early identification and early management 9. This was related to implementation of sepsis bundle within one hour, which includes Measure lactate level, obtain blood cultures prior to administration of antibiotics, administer broad-spectrum antibiotics, rapidly administer 30 mL/kg crystalloid for hypotension or lactate ≥ 4 mmol/L, apply vasopressors if patient is hypotensive during or after fluid resuscitation to maintain mean arterial pressure ≥ 65 mm Hg 10.

Empiric broad-spectrum therapy with one or more intravenous antimicrobials to cover all likely pathogens should be started immediately for patients presenting with sepsis or septic shock and should be narrowed once pathogen identification and sensitivities are established 11. High mortality was linked to delayed administration of antibiotics and with inappropriate antibiotics therapy 11, 12.

In Sudan the incidence of sepsis is likely to be rising, data about sepsis and septic shock mortality is deficient. The lack of data about most common micro-organisms and antibiotic sensitivity patterns led to the deficiency of local empirical antibiotic guidelines. The aim of this study was to assess the impact and appropriateness of empirical antibiotic choice on the clinical outcomes of sepsis and septic shock in intensive care department.

2. Material and Methods

This is a cross-sectional hospital-based study, conducted in the ICU in Fedail specialized hospital (10 beds) and Aliaa specialized hospital (15 beds), Khartoum, Sudan, between 01/9/2018 to 30/10/ 2018. Data related to all Adult Patient (≥18-year-old) with sepsis and septic shock admitted to the ICU was collected. Data was abstracted and collected from the patients' records sheets in the hospital by structured questionnaire. The questionnaire covered patients' demographic data, reasons for admission, sepsis related risk factor, site of infection, timing of the blood culture sampling, culture result and administration of antibiotics. Hospital length of stay and mortality were measured.

Data analysis was managed using statistical package for social science (SPSS) for windows version 20. Chi-square test was used to test for significant difference between the variables. P. value < 0.05 was considered statistically significant. Ethical approval was obtained from the Sudan Medical Specialization Board (S.M.S.B). Confidentiality was maintained through using coded questionnaires. Permission was obtained from authorities in Fedail hospital and Aliaa hospital.

3. Results

Data was collected from 53 patients admitted to the ICUs. Females were 31 (58%) and 27 (50.9%) of the patients were older than 65 years as shown in (Table 1). sepsis and septic shock were reported in 30 (57%) and 23 (43%) of patient respectively.

Almost one third (34%) of patient has no identifiable risk factor. The most common risk factors were recent hospitalization within past 3 months (32%), diabetes mellitus (15%), cancer/chemotherapy (9%), chronic kidney disease (8%) and congestive heart failure (2%), (Table 2).

Respiratory tract infections were the most common source of infection (34%). While in 11.3% of patients, the site of infection was not identified. Other sites of infection included; urinary tract infection, 18.9%; abdomen, 15.1%; skin, 9.4%; central nervous system, 7.5% and intravenous catheter related sepsis was the least common, 3.8%. (Table 2)

Among the study population, 91% had a sample taken for culture and sensitivity; of them 52.8% were taken before starting of empirical antibiotics. In 22.6% were taken after receiving antibiotics, while in 24.5% there was no documented evidence of the timing of culture sample collection.

Most of the patients (81.1%) received a combination of empirical antibiotics compared to 18.9% who received single empirical antibiotic. More than one third (37%) of those who received combination empirical antibiotics were discharged from the ICU, compared to only 10% of those receiving single empirical antibiotic. This was not statistically significant, P= 0.097.

The culture results obtained from 48 patients showed 37 were positive and 11 were negative by the fifth day. Only 22% (n=8) of the culture results showed that the initial empirical antibiotic was sensitive, while the rest 78% (n=29) showed that the initial empirical antibiotic was not sensitive. Of the latter group the antibiotic was changed according to the culture results in 65.5% (n=19). The rates of discharge from hospital were 87.5% and 17.2% of patients in whom initial empirical antibiotic was sensitive and resistant respectively, P value was statistically significant, p = 0.001.

In the study population, 67.9% (n=36) of patients died in the ICU. Most of them suffered for septic shock in 58 % (n=21), P value = 0.001 and it was statistically significant (Table 3).

4. Discussion

In this study the majority of patients (50.9%) were older than 65 years; this result is consistent with other studies that put age as independent risk factor for developing sepsis and organ dysfunction 13. Although one third of the patients (34%) have no identifiable risk factor, recent hospitalization was reported in 32% of patient. Hospitalization was reported to be associated with increased antibiotic resistant infections; this impact the selection of appropriated antibiotic 14, 15. Diabetes, congestive heart failure and chronic renal disease were found in one third of the study population. Sakr Y et al, reported that chronic illnesses, cancer therapy, mechanical ventilation, use of renal replacement therapy and infection with Acinetobacter are considered as independent risk factors for in-hospital death 16.

Respiratory tract infections were the most common site of infection (34%). Many studies found that respiratory tract infections are the most common site of infection, and associated with the highest mortality 17. In this study the site of infection was not correlated to mortality. This can be explained by the lack of the effectiveness of empirical antibiotics in our study. Annane et al, analyzed data from 100,554 patients from 1993-2000, and found an increased trend in respiratory infection and multi-resistant bacterial related septic shock (P=0.001 for both) 18.

In quarter of patients there was no documented evidence of the timing of culture sample collection and this may reflect a poor documentation and the lack of the appropriate pathways for sepsis identification and management. Obtaining culture result is essential for definite diagnosis of sepsis and septic shock, having only clinical features without microbial documentation makes the diagnosis just likely 19. Greig JR, reviewed the accuracy of documentation of blood culture results in a hospital in UK, he found that 26% of the reviewed results were not documented in the patient's records 20. The use of appropriate antibiotics is associated with reduction in the mortality rate, but their adequacy will not be assured without antimicrobial documentation 21.

The use of combination antibiotics broadens the antibacterial spectrum of the empirical therapy 22. Although our study had reported the use of combination empirical antibiotics in the majority of patients (81%), there was no significant relationship between the number of empirical antibiotic and mortality rates. This is different from results obtained by evaluation of 4664 cases of culture positive septic shock between 1996 and 2007, which had revealed decrease in hospital and ICU mortality with the use of combination therapy rather than monotherapy. In addition, there was increase in ventilator and inotrope/presser free days 23. This is call for assessing the tools of appropriate empirical antimicrobial selection in our study.

According to our knowledge, Sudan lacks a national empirical antibiotic guideline; hospitals as well have no local empirical therapy guidelines. Therefore the choice of empirical antibiotic was not guided by a local sensitivity profiles. This resulted in only 24% of the culture results to be compatible with the initial empirical antibiotic. The majority (76%) showed that the initial empirical antibiotic was not sensitive. Patients received initial sensitive empirical antibiotic had higher ICU discharge and lower mortality rates compared to patients who received initial empirical antibiotic which was not sensitive on culture results.

The use of initial empirical antimicrobial therapy depends on the clinical presentation; therefore the usual way is to give broad spectrum therapy that targets the possible pathogens 24. Moreover, there are many factors that influence the selection of the empirical therapy such as: site of infection, comorbidities, immune status and the local antimicrobial resistance 15, 24. While factors such as recent hospitalization and prior infection with resistant organism, should raise the need for antimicrobial therapy that covers MRSA and VRS 15. In study done among 524 ICU patients, Buising KL et al, compared the initial antibiotic therapy with the microbiological lab results, they reported around 14% of sterile isolate and nearly one third of non-sterile isolate were associated with the use of inadequate empirical antimicrobial therapy against the identified bacteria 25.

In the study population 67.9% of patients died in the ICU, which is considered high compared to other studies 26. The initial diagnosis of septic shock was associated with higher mortality compared to patients with sepsis (p less than 0.5). In some studies the mortality rate from septic shock reaches up to 50% 27.

5. Limitations

The study included only two hospitals and didn’t take into account the factor of delayed antibiotic administration, in addition to small sample size.

6. Conclusion

In conclusion, this study shows that the use of appropriate empirical antibiotics would result in better patient outcomes.

7. Recommendations

The study needs to be conducted in larger group of patients. Future studies should include the isolated micro-organisms and the sensitivity patterns.

References

[1]  Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA [Internet]. American Medical Association; 2016 Feb 23 [cited 2018 Oct22]; 315(8): 801.
In article      
 
[2]  Gestel A Van, Bakker J, Veraart CPWM, Hout BA Van, van Gestel A, van Hout B a. Prevalence and incidence of severe sepsis in Dutch intensive care units. Crit Care [Internet]. 2004; 8(4): R153-62.
In article      View Article  PubMed
 
[3]  Brun-Buisson C, Minelli C, Bertolini G, Brazzi L, Pimentel J, Lewandowski K, et al. Epidemiology and outcome of acute lung injury in European intensive care units Results from the ALIVE study. Intensive Care Med. 2004; 30(1): 51-61.
In article      View Article  PubMed
 
[4]  Martin GS, Mannino DM, Eaton S, Moss M. The Epidemiology of Sepsis in the United States from 1979 through 2000. N Engl J Med [Internet]. 2003; 348(16): 1546-54.
In article      View Article  PubMed
 
[5]  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.
In article      View Article  PubMed
 
[6]  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): 1-10.
In article      View Article  PubMed
 
[7]  Dagher GA, Saadeldine M, Bachir R, Zebian D, Chebl RB. Descriptive analysis of sepsis in a developing country. Int J Emerg Med [Internet]. SpringerOpen; 2015 Dec 6 [cited 2018 Oct 27]; 8(1): 19.
In article      View Article  PubMed
 
[8]  Gasim GI, Musa IR, Yassin T, Al Shobaili HA, Adam I. Sepsis in Buraidah Central Hospital, Qassim, Kingdom of Saudi Arabia. Int J Health Sci (Qassim) [Internet]. Qassim University; 2016 Apr [cited 2018 Oct 27]; 10(2): 175-81.
In article      View Article
 
[9]  Jones SL, Ashton CM, Kiehne L, Gigliotti E, Bell-Gordon C, Disbot M, Masud F, Shirkey BA, Wray NP. Reductions in sepsis mortality and costs after design and implementation of a nurse-based early recognition and response program. The Joint Commission Journal on Quality and Patient Safety. 2015 Nov 1; 41(11): 483-AP3.
In article      View Article
 
[10]  Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med. 2018; 46(6): 997-1000.
In article      View Article  PubMed
 
[11]  Bernhard M, Lichtenstern C, Eckmann C, Weigand MA. The early antibiotic therapy in septic patients - milestone or sticking point? Crit Care [Internet]. BioMed Central; 2014 Dec 30 [cited 2018 Oct 28]; 18(6): 671.
In article      View Article  PubMed
 
[12]  Marquet K, Liesenborgs A, Bergs J, Vleugels A, Claes N. Incidence and outcome of inappropriate in-hospital empiric antibiotics for severe infection: a systematic review and meta-analysis. Critical care. 2015 Dec 1; 19(1): 63.
In article      View Article  PubMed
 
[13]  Mayr FB, Yende S, Linde-Zwirble WT, Peck-Palmer OM, Barnato AE, Weissfeld LA, et al. Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis. JAMA [Internet]. American Medical Association; 2010 Jun 23 [cited 2018 Oct 24]; 303(24): 2495.
In article      View Article  PubMed
 
[14]  Mainous III AG, Diaz VA, Matheson EM, Gregorie SH, Hueston WJ. Trends in hospitalizations with antibiotic-resistant infections: US, 1997–2006. Public Health Reports. 2011 May; 126(3): 354-60.
In article      View Article  PubMed
 
[15]  Leekha S, Terrell CL, Edson RS. General principles of antimicrobial therapy. InMayo Clinic Proceedings 2011 Feb 1 (Vol. 86, No. 2, pp. 156-167). Elsevier.
In article      View Article  PubMed
 
[16]  Sakr Y, Jaschinski U, Wittebole X, Szakmany T, Lipman J, Ñamendys-Silva SA, Martin-Loeches I, Leone M, Lupu MN, Vincent JL, ICON Investigators. Sepsis in intensive care unit patients: worldwide data from the intensive care over nations audit. InOpen forum infectious diseases 2018 Dec (Vol. 5, No. 12, p. ofy313). US: Oxford University Press.
In article      View Article  PubMed
 
[17]  Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014 Jan 1; 5(1): 4-11.
In article      View Article  PubMed
 
[18]  Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current epidemiology of septic shock: the CUB-Rea Network. American journal of respiratory and critical care medicine. 2003 Jul 15; 168(2): 165-72.
In article      View Article  PubMed
 
[19]  Annane D, Bellissant E, Cavaillon JM. Septic shock. The Lancet. 2005 Jan 1; 365(9453): 63-78.
In article      View Article
 
[20]  Greig JR. Accuracy and completeness of the documentation of blood culture results. Journal of clinical pathology. 2003 Jul 1; 56(7): 558.
In article      View Article  PubMed
 
[21]  Opota O, Croxatto A, Prod'hom G, Greub G. Blood culture-based diagnosis of bacteraemia: state of the art. Clinical Microbiology and Infection. 2015 Apr 1; 21(4): 313-22.
In article      View Article  PubMed
 
[22]  Micek ST, Welch EC, Khan J, Pervez M, Doherty JA, Reichley RM, et al. Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to Gram-negative bacteria: a retrospective analysis. Antimicrob Agents Chemother [Internet]. American Society for Microbiology Journals; 2010 May 1 [cited 2018 Oct 28]; 54(5): 1742-8.
In article      View Article  PubMed
 
[23]  Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D, Laporta D, Lapinsky S, Ellis P, Mirzanejad Y, Martinka G. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Critical care medicine. 2010 Sep 1; 38(9): 1773-85.
In article      View Article  PubMed
 
[24]  Liang SY, Kumar A. Empiric antimicrobial therapy in severe sepsis and septic shock: optimizing pathogen clearance. Current infectious disease reports. 2015 Jul 1; 17(7): 36.
In article      View Article  PubMed
 
[25]  Buising KL, Thursky KA, Bak N, Skull S, Street A, Presneill JJ, Cade JF, Brown GV. Antibiotic prescribing in response to bacterial isolates in the intensive care unit. Anaesthesia and intensive care. 2005 Oct; 33(5): 571-7.
In article      View Article  PubMed
 
[26]  Siddiqui S. Mortality profile across our intensive care units: a 5-year database report from a Singapore restructured hospital. Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2015 Dec; 19(12): 726.
In article      View Article  PubMed
 
[27]  Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nature reviews Disease primers. 2016 Jun 30; 2(1): 1-21.
In article      View Article  PubMed
 

Published with license by Science and Education Publishing, Copyright © 2020 Ihab B. Abdalrahman, Shaima N Elgenaid, Galal Mohamedani and Mohammed Elfatih Ahmed Yousif

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Normal Style
Ihab B. Abdalrahman, Shaima N Elgenaid, Galal Mohamedani, Mohammed Elfatih Ahmed Yousif. Impact of Empirical Antibiotic Choice on the Clinical Outcomes of Patients Admitted to ICU with Sepsis and Septic Shock. American Journal of Educational Research. Vol. 8, No. 9, 2020, pp 727-730. http://pubs.sciepub.com/education/8/9/15
MLA Style
Abdalrahman, Ihab B., et al. "Impact of Empirical Antibiotic Choice on the Clinical Outcomes of Patients Admitted to ICU with Sepsis and Septic Shock." American Journal of Educational Research 8.9 (2020): 727-730.
APA Style
Abdalrahman, I. B. , Elgenaid, S. N. , Mohamedani, G. , & Yousif, M. E. A. (2020). Impact of Empirical Antibiotic Choice on the Clinical Outcomes of Patients Admitted to ICU with Sepsis and Septic Shock. American Journal of Educational Research, 8(9), 727-730.
Chicago Style
Abdalrahman, Ihab B., Shaima N Elgenaid, Galal Mohamedani, and Mohammed Elfatih Ahmed Yousif. "Impact of Empirical Antibiotic Choice on the Clinical Outcomes of Patients Admitted to ICU with Sepsis and Septic Shock." American Journal of Educational Research 8, no. 9 (2020): 727-730.
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[1]  Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA [Internet]. American Medical Association; 2016 Feb 23 [cited 2018 Oct22]; 315(8): 801.
In article      
 
[2]  Gestel A Van, Bakker J, Veraart CPWM, Hout BA Van, van Gestel A, van Hout B a. Prevalence and incidence of severe sepsis in Dutch intensive care units. Crit Care [Internet]. 2004; 8(4): R153-62.
In article      View Article  PubMed
 
[3]  Brun-Buisson C, Minelli C, Bertolini G, Brazzi L, Pimentel J, Lewandowski K, et al. Epidemiology and outcome of acute lung injury in European intensive care units Results from the ALIVE study. Intensive Care Med. 2004; 30(1): 51-61.
In article      View Article  PubMed
 
[4]  Martin GS, Mannino DM, Eaton S, Moss M. The Epidemiology of Sepsis in the United States from 1979 through 2000. N Engl J Med [Internet]. 2003; 348(16): 1546-54.
In article      View Article  PubMed
 
[5]  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.
In article      View Article  PubMed
 
[6]  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): 1-10.
In article      View Article  PubMed
 
[7]  Dagher GA, Saadeldine M, Bachir R, Zebian D, Chebl RB. Descriptive analysis of sepsis in a developing country. Int J Emerg Med [Internet]. SpringerOpen; 2015 Dec 6 [cited 2018 Oct 27]; 8(1): 19.
In article      View Article  PubMed
 
[8]  Gasim GI, Musa IR, Yassin T, Al Shobaili HA, Adam I. Sepsis in Buraidah Central Hospital, Qassim, Kingdom of Saudi Arabia. Int J Health Sci (Qassim) [Internet]. Qassim University; 2016 Apr [cited 2018 Oct 27]; 10(2): 175-81.
In article      View Article
 
[9]  Jones SL, Ashton CM, Kiehne L, Gigliotti E, Bell-Gordon C, Disbot M, Masud F, Shirkey BA, Wray NP. Reductions in sepsis mortality and costs after design and implementation of a nurse-based early recognition and response program. The Joint Commission Journal on Quality and Patient Safety. 2015 Nov 1; 41(11): 483-AP3.
In article      View Article
 
[10]  Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med. 2018; 46(6): 997-1000.
In article      View Article  PubMed
 
[11]  Bernhard M, Lichtenstern C, Eckmann C, Weigand MA. The early antibiotic therapy in septic patients - milestone or sticking point? Crit Care [Internet]. BioMed Central; 2014 Dec 30 [cited 2018 Oct 28]; 18(6): 671.
In article      View Article  PubMed
 
[12]  Marquet K, Liesenborgs A, Bergs J, Vleugels A, Claes N. Incidence and outcome of inappropriate in-hospital empiric antibiotics for severe infection: a systematic review and meta-analysis. Critical care. 2015 Dec 1; 19(1): 63.
In article      View Article  PubMed
 
[13]  Mayr FB, Yende S, Linde-Zwirble WT, Peck-Palmer OM, Barnato AE, Weissfeld LA, et al. Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis. JAMA [Internet]. American Medical Association; 2010 Jun 23 [cited 2018 Oct 24]; 303(24): 2495.
In article      View Article  PubMed
 
[14]  Mainous III AG, Diaz VA, Matheson EM, Gregorie SH, Hueston WJ. Trends in hospitalizations with antibiotic-resistant infections: US, 1997–2006. Public Health Reports. 2011 May; 126(3): 354-60.
In article      View Article  PubMed
 
[15]  Leekha S, Terrell CL, Edson RS. General principles of antimicrobial therapy. InMayo Clinic Proceedings 2011 Feb 1 (Vol. 86, No. 2, pp. 156-167). Elsevier.
In article      View Article  PubMed
 
[16]  Sakr Y, Jaschinski U, Wittebole X, Szakmany T, Lipman J, Ñamendys-Silva SA, Martin-Loeches I, Leone M, Lupu MN, Vincent JL, ICON Investigators. Sepsis in intensive care unit patients: worldwide data from the intensive care over nations audit. InOpen forum infectious diseases 2018 Dec (Vol. 5, No. 12, p. ofy313). US: Oxford University Press.
In article      View Article  PubMed
 
[17]  Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014 Jan 1; 5(1): 4-11.
In article      View Article  PubMed
 
[18]  Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current epidemiology of septic shock: the CUB-Rea Network. American journal of respiratory and critical care medicine. 2003 Jul 15; 168(2): 165-72.
In article      View Article  PubMed
 
[19]  Annane D, Bellissant E, Cavaillon JM. Septic shock. The Lancet. 2005 Jan 1; 365(9453): 63-78.
In article      View Article
 
[20]  Greig JR. Accuracy and completeness of the documentation of blood culture results. Journal of clinical pathology. 2003 Jul 1; 56(7): 558.
In article      View Article  PubMed
 
[21]  Opota O, Croxatto A, Prod'hom G, Greub G. Blood culture-based diagnosis of bacteraemia: state of the art. Clinical Microbiology and Infection. 2015 Apr 1; 21(4): 313-22.
In article      View Article  PubMed
 
[22]  Micek ST, Welch EC, Khan J, Pervez M, Doherty JA, Reichley RM, et al. Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to Gram-negative bacteria: a retrospective analysis. Antimicrob Agents Chemother [Internet]. American Society for Microbiology Journals; 2010 May 1 [cited 2018 Oct 28]; 54(5): 1742-8.
In article      View Article  PubMed
 
[23]  Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D, Laporta D, Lapinsky S, Ellis P, Mirzanejad Y, Martinka G. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Critical care medicine. 2010 Sep 1; 38(9): 1773-85.
In article      View Article  PubMed
 
[24]  Liang SY, Kumar A. Empiric antimicrobial therapy in severe sepsis and septic shock: optimizing pathogen clearance. Current infectious disease reports. 2015 Jul 1; 17(7): 36.
In article      View Article  PubMed
 
[25]  Buising KL, Thursky KA, Bak N, Skull S, Street A, Presneill JJ, Cade JF, Brown GV. Antibiotic prescribing in response to bacterial isolates in the intensive care unit. Anaesthesia and intensive care. 2005 Oct; 33(5): 571-7.
In article      View Article  PubMed
 
[26]  Siddiqui S. Mortality profile across our intensive care units: a 5-year database report from a Singapore restructured hospital. Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2015 Dec; 19(12): 726.
In article      View Article  PubMed
 
[27]  Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nature reviews Disease primers. 2016 Jun 30; 2(1): 1-21.
In article      View Article  PubMed