Subscribe to RSS

DOI: 10.1055/s-0044-1786002
Comparative Analysis of Surgical Site Infections in Pediatric Brain Tumor Patients: Hygiene Practices, Risk Factors, and Implications for Healthcare Costs and Mortality
- Introduction
- Methods
- Statistical Analysis
- Results
- Discussion
- Conclusion
- Limitations and Strengths
- References
Abstract


Surgical site infections (SSIs) significantly impact pediatric central nervous system tumor outcomes. We present our data of SSIs and their influence on outcomes of pediatric brain tumor patients treated between January 2011 till December 2022. This study utilized retrospective data from patients' medical records. Chi-squared test was used for correlational analysis. Independent sample t-test was used for equality of means. Linear and logistic regression was done to review impact of independent variables on dependent variable. Survival analysis was done using Kaplan–Meier curves. Between 2011 and 2022, 336 pediatric patients (202 males, 134 females) were diagnosed with brain tumors. Majority patients (279; 83%) underwent surgery (91% elective). Commonest tumor site was cerebellum (84/279; 30%). Tumor resection status was gross total resection (29/279; 46%), subtotal resection (59/279; 21%), near total resection (48/279; 17%), and partial resection (20/279; 7%); while 32/279 patients (11%) had a biopsy only. Hydrocephalus was present in 166/279 patients (59%); while majority (160/166; 96%) underwent a cerebrospinal fluid (CSF) diversion procedure. SSI developed in 23/279 patients (8%), leading to delayed postoperative management in majority (15/23; 65%). SSIs were significantly associated with lower age of presentation (p = 0.01), less duration between symptoms and diagnosis (p = 0.00), performance of CSF diversion procedure (p = 0.04), increase in hospital stay (p = 0.00), delay in postoperative management (15/23; 65%) (p = 0.01), decline in treatment completion (p = 0.01), and poor survival (p = 0.01). Majority (171/279) of patients (61%) completed treatment. The overall survival of our cohort was 84.9% with a median follow-up time of 11 (interquartile range [IQR]: 36, 1) months. Survival was significantly lower (56.5%) in patients with SSI (p = 0.01). Median time to death was 18 months. Progression-free survival was 77.4% with a median progression-free time of 8 (IQR: 28, 1) months. Median time to progression was 9 (IQR: 24, 4.5) months. The incidence of SSIs in our cohort closely resembled that of high-income countries. Risk factors for SSIs included younger age, a shorter time between symptom onset and surgery, undertaking of CSF diversion procedures. Adverse effects of SSIs included increased costs, delays in postoperative management, incomplete treatment, and higher mortality rates. This study emphasizes the substantial impact of SSIs on healthcare resources and patient well-being.
#
Introduction
Significant variation exists between the incidence of primary central nervous system tumors between high- and low- to middle-income countries (LMICs).[1] More than 90% of children at risk of developing childhood cancer each year live in LMICs.[2] Outcomes of these children are relatively good in high-income countries (HICs); however, in LMICs, outcomes are notably less optimistic.
For pediatric brain tumors, surgical resection remains the primary step of treatment.[3] However, neurosurgery is associated with morbidity and mortality due to surgical site infections (SSIs).
The objectives of this study are to conduct an internal quality control, and to compare our findings with international outcomes. We aim to establish benchmark parameters for institutional practices that can be adopted by smaller, less specialized centers in the field.
#
Methods
This study involved retrospective review of patients' charts, diagnosed and treated for brain tumor, 0 to 18 years, from January 2011 till December 2022. Magnetic resonance imaging brain with contrast was used for initial confirmation of diagnosis, with a standardized formula of length x width x thickness x 0.523 to calculate tumor volumes.[4] Those who did not opt for surgery were removed from the analysis list. Tumors were classified according to World Health Organization (WHO) classification of tumors.[5]
All patients received postoperative dexamethasone to manage peritumoral edema and perioperative parenchymal swelling.[6] Resection status was described following the guidelines provided by Karschnia et al as follows: Gross total resection (GTR; removal of 100% of the tumor), near total resection (NTR; removal of >95% of the tumor), subtotal resection (STR; removal of ≥80% of the tumor), partial resection (PR; removal of 1-79% of the tumor), and biopsy (performed solely for diagnostic purposes).[7]
Files were systematically reviewed, encompassing postoperative notes, daily progress notes, and lab results, to identify patients who developed SSI. SSI was defined as any infection occurring near or at the incision site and/or deeper underlying tissue spaces and organs within 30 days of a surgical procedure.[8] SSIs included suppuration of wounds, scalp abscess, meningitis, ventriculitis, and intracerebral abscess. Meningitis was diagnosed on the basis of cerebrospinal fluid (CSF) detailed report and culture and sensitivity (CS).[9] Patients with deep infections were initially treated empirically with ceftriaxone and vancomycin, with adjustment of antibiotics guided by CSF CS reports. In case of deterioration in the patient's condition, an escalation of antibiotics to include meropenem, vancomycin, and colistin was implemented. Criteria of stopping antibiotics were total 14 days of treatment, with at least 10 days post-negative CSF and blood cultures, given that the patient achieved afebrile status and there was observable clinical improvement.[10]
Qualitative data included gender, residence, site of tumor, completion of treatment; presence, type, site of SSI, sensitivity of organisms, type of treatment received, prophylactic antibiotics received, acute postsurgical complications, and long-term sequalae. Continuous data included age, height, weight at diagnosis, volume of tumor, duration between symptoms onset and surgery, length of surgery, length of hospital stay, and dose of radiation therapy. Last date of follow-up was used to calculate survival time. Progression was confirmed radiologically.
#
Statistical Analysis
Since our data was not normally distributed, median and frequencies were calculated for quantitative and qualitative variables, respectively. Pearson chi-squared test was used to calculate correlation between qualitative variables. Independent sample t-test was used to calculate difference between means of two groups. Regression (linear and logistic) analysis was performed on variables that showed significant (p ≤ 0.05) correlation. Kaplan–Meier survival curves were used to calculate survival analysis. Log-rank test was used to compare survival between two groups. A p-value of less than or equal to 0.05 was considered significant. All data was analyzed using Statistical Package for the Social Sciences (SPSS) v22.
#
Results
From 2011 to 2022, 339 pediatric patients (202 males, 134 females) were diagnosed with brain tumors, with a median age of 108 (IQR: 170, 60) months (9 years) and a median duration between symptom onset and surgery of 60 (IQR: 180, 21) days ([Table 1]). Out of the total, 279 patients (83%) underwent neurosurgery and were included in the study.
Abbreviations: CP, cerebellopontine; CSF, cerebrospinal fluid; XRT, radiation therapy
Cerebellum was the commonest site of tumor presentation (101/339; 30%; [Fig. 1]). Median primary tumor volume was 36.85 (IQR: 86.5, 20) mL. Metastatic disease was present in 20/279 patients (7%). Hydrocephalus was present in half of the patients (166/279; 59%). Most frequent pathological diagnosis was circumscribed astrocytic glioma (74/279; 26%) ([Table 2]). Cancer predisposition syndrome testing was conducted in 74 out of 279 patients, with 30 testing positive (p53 mutation 29, constitutional mismatch repair deficiency [CMMRD] 1); the majority (73.3%) of positive cases were identified in diffuse high-grade gliomas ([Table 3]).


Abbreviations: CNS, central nervous system; NOS, not otherwise specified.
Abbreviations: CMMRD, constitutional mismatch repair deficiency; CSF, cerebrospinal fluid; SSI, surgical site infection.
All patients received presurgery prophylactic antibiotics. Majority underwent elective surgery (255/279; 91%) ([Table 2]), with a median surgery duration of 4 (interquartile range [IQR]: 5.5, 2.5) hours. Craniotomy was the predominant procedure (275/279; 99%), with the commonest surgical approach being occipital (144/279; 52%). Resection status was GTR (129/279; 46%), STR (59/279; 21%), NTR (48/279; 17%), PR (20/279; 7%); while 32/279 (11%) patients underwent a biopsy only.
Majority with hydrocephalus (160/166; 96%) underwent a CSF diversion procedure (extraventricular drain [EVD] commonest 108/160; 67%), with majority (116/160; 72%) having CSF diversion at the time of tumor resection/biopsy. Thirty-nine (39/108; 36%) patients with EVD underwent subsequent ventriculoperitoneal shunting procedure, at a median time of 8 (range: 2–28) days.
Acute postsurgical complications developed in 107/279 (38%) patients, commonest being neurological (69/107; 64%). The incidence of other complications was; infections other than SSI (35/107; 33%), electrolytes imbalance (15/107; 14%), endocrinological (13/107; 12%), postoperative hematoma (10/107; 9%), CSF leak from wound site (10/107; 9%), and posterior fossa syndrome (10/107; 9%; [Table 3]).
The incidence of SSIs was 23/279 (8%; [Table 3]). Notably, all cases of SSI were deep-seated infections. Only 8/23 (35%) patients had a positive growth in CSF culture. The infective organisms identified were Staphylococcus aureus 2, Acinetobacter 2, Escherichia coli 1, Klebsiella pneumoniae 1, Aspergillus flavus 1, and Candida albicans 1. Average duration of hospitalization for patients who developed SSI was 20 days, in contrast to 8 days in those without SSI (P = 0.004).
Majority patients in our cohort (171/279; 61%) completed treatment for their cancer. Treatment abandonment was observed in 82/279 patients (29%), while 26/279 (9%) patients were unable to complete treatment due to postsurgical complications. Seventy-one (71/171; 41%) and (63/171; 37%) received chemotherapy and radiation therapy, respectively ([Table 1], [Figs. 2] and [3]).




SSIs were significantly associated with presence of hydrocephalus (hazard ratio [HR]: 1.124; 95% confidence interval [CI]: 1.029–1.542; p = 0.050), performance of CSF diversion procedure (HR: 1.053; 95% CI: 1.007–1.400; p = 0.040), CSF leakage from wound site (HR: 1.886, 95% CI: 1.561–1.970, p = 0.002), increase in in-hospital stay of patients (HR: 1.143; 95% CI: 1.09–1.192; p = 0.000), delay in postoperative management (15/23; 65%) (HR: 1.983; 95% CI: 1.938–1.995; p = 0.010), decline in treatment completion (HR: 0.179; 95% CI: 0.837–0.915; p = 0.015), as well as poor survival (HR: 5.385; 95% CI: 2.181–13.294; p = 0.010); while there was inverse correlation between age of diagnosis and SSI (HR: 0.991; 95% CI: 0.984–0.999; p = 0.018; [Table 4]).
Abbreviations: CI, confidence interval; CSF, cerebrospinal fluid; HR, hazard ratio; SSI, surgical site infection.
The overall survival of our cohort was 84.9% with a median follow-up time of 11 (IQR: 36, 1) months ([Fig. 4]). Survival was significantly lower (56.5%) in patients with SSI (p = 0.010; [Fig. 5]). Median time to death was 18 months. Primary disease progressed in (63/279;22%) patients. The progression-free survival was 77.4% with a median progression-free time of 8 (IQR: 28, 1) months ([Fig. 6]). Median time to progression was 9 (IQR: 24, 4.5) months.






#
Discussion
SSIs represent a potentially preventable source of postoperative complications, mortality, and financial strain particularly in LMICs. The heightened occurrence of SSIs in LMICs is attributed to factors such as inadequate sterility, environmental pollution, compromised immunity, antibiotic resistance, and suboptimal vaccination coverage.[11] The incidence reported from other centers in Pakistan is approximately 29 to 35%.[12] Our study reports an SSI incidence of 8%.
Our data highlights that the performance of CSF diversion procedures is associated with an elevated risk of SSIs. Same has been identified in other studies.[13] [14] This highlights the importance of avoiding CSF diversion procedures unless necessary. Implementation of a preshunt surgery checklist for infection control can effectively reduce the SSI rate attributable to this preventable cause, as reported by Lee et al.[15]
Inverse correlation was observed between age and the risk of SSI, aligning with the findings by Boethun et al.[16] However, contrasting results have been reported by others. The conflicting findings highlight the need for further studies to establish a more definitive understanding of the relationship between age and the risk of SSI.
The incidence CSF leakage (3.7%) was higher in those undergoing infratentorial surgery compared to those with supratentorial surgeries (6 vs. 4) ([Table 5]); this, however, was not statistically significant (p = 0.434). Notably, no significance was found between craniotomy and craniectomy concerning CSF leakage, as the majority of our patients underwent craniotomy.
Abbreviations: CSF, cerebrospinal fluid; EVD, extraventricular drain; VPS, ventriculoperitoneal shunt.
A significant association was observed between SSI and disease progression (p = 0.007). SSIs understandably result in delays in postsurgical management, including the administration of chemotherapy and radiation therapy. These delays ultimately contribute to disease progression.
An interesting finding in our study was the significant influence of the duration between symptom onset and surgery on the incidence of SSI. Notably, individuals with a longer duration of symptoms before surgery (229 vs. 80 days) exhibited a decreased incidence of SSIs (p = 0.000). High-grade tumors often prompt early presentation and the development of hydrocephalus.[17] [18] Individuals who underwent CSF diversion had a shorter duration between symptom onset and surgery (127 vs. 339 days; p = 0.00). Similarly, those with poorer survival outcomes also demonstrated a shorter duration between symptoms and surgery (79 vs. 242 days; p = 0.00; [Table 6]).
Abbreviation: SSI, surgical site infection.
Positive antimicrobial growth was observed in 35% (8/23) of our patients with SSI. Consistent with literature, mixed flora, encompassing both gram-positive and gram-negative organisms, was identified. Notably, fungal species growth was detected in two patients, a noteworthy finding as fungal growth is infrequently reported.
SSIs contribute to a spectrum of adverse effects, including prolonged hospital stays,[19] which also elevates the risk of hospital-acquired infections, further prolonging the stay. In our study, the average extra length of stay due to SSI was 11.5 days (p = 0.004), representing a substantial wastage of healthcare resources.
Lastly, SSIs resulted in delays in postoperative care and a decline in the completion of treatment. These factors collectively had a detrimental impact on the overall survival of our cohort, with statistically significant differences observed in survival durations: (8.5 vs. 23.7 months; p = 0.00) and (5.98 vs. 33.60 months; p = 0.00), respectively.
Based on the above findings, we advocate strict adherence to the WHO guidelines for SSI prevention.[20] These guidelines encompass the following key measures: I) Whenever possible, consider the use of oral/enteral nutrient-enhanced formulas for underweight patients to ensure adequate nutritional status before surgery. II) Patients should undergo a preoperative bath or shower, utilizing either plain soap or an antimicrobial soap. III) Consider perioperative intranasal applications of mupirocin 2% ointment, either alone or in combination with chlorhexidine gluconate (CHG) bodywash. IV) Avoid hair removal whenever possible. If necessary, use clippers instead of shaving, as shaving is strongly discouraged both preoperatively and in the operating room. V) Administer antibiotic prophylaxis within 120 minutes before incision. VI) Utilize alcohol-based antiseptic solutions containing CHG for surgical site skin preparation. VII) Refrain from using antimicrobial sealants following surgical site skin preparation. VIII) Minimize the utilization of CSF diversion procedures whenever feasible.
#
Conclusion
The occurrence of SSIs in our cohort mirrored that of HICs. Identified risk factors for SSIs included younger age, a shorter interval between symptom onset and surgery, the presence of hydrocephalus, and the performance of CSF diversion procedures.
Notably, SSIs in our study were linked to substantial additional costs and elevated mortality rates. Delays in postoperative management and incomplete treatment significantly contributed to these outcomes, underscoring the multifaceted impact of SSIs on healthcare resources and patient well-being.
#
Limitations and Strengths
Our study is retrospective in nature, and it may not fully address the gaps in patient records. Several confounding factors, such as variations in tumor pathology, could have potentially influenced the outcomes. Treatment protocols were not standardized across all patients, and surgeries were conducted by different surgeons with varying levels of expertise, potentially contributing to variations in SSIs. However, this study offers valuable insight into the causes and consequences of SSI in children with brain tumors, and serves as a catalyst for further endeavors aimed at reducing the occurrence of such infections.
#
#
Conflict of Interest
None declared.
Ethical Approval
Ethical review committee approval was obtained via letter number 2023-9316-26871, dated October 23rd, 2023.
-
References
- 1 Hossain MJ, Xiao W, Tayeb M, Khan S. Epidemiology and prognostic factors of pediatric brain tumor survival in the US: evidence from four decades of population data. Cancer Epidemiol 2021; 72: 101942
- 2 Bhakta N, Force LM, Allemani C. et al. Childhood cancer burden: a review of global estimates. Lancet Oncol 2019; 20 (01) e42-e53
- 3 Udaka YT, Packer RJ. Packer RJJNc. Pediatric brain tumors. Neurol Clin 2018; 36 (03) 533-556
- 4 Bathla G, Policeni B, Hansen MR, Berbaum K. Calculating the tumor volumes in vestibular schwannomas: are the ABC/2 and volumetric methods comparable?. Otol Neurotol 2017; 38 (06) 889-894
- 5 Louis DN, Perry A, Wesseling P. et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-oncol 2021; 23 (08) 1231-1251
- 6 Palombi L, Marchetti P, Salvati M, Osti MF, Frati L, Frati A. Interventions to reduce neurological symptoms in patients with GBM receiving radiotherapy: from theory to clinical practice. Anticancer Res 2018; 38 (04) 2423-2427
- 7 Karschnia P, Vogelbaum MA, van den Bent M. et al. Evidence-based recommendations on categories for extent of resection in diffuse glioma. Eur J Cancer 2021; 149: 23-33
- 8 Borchardt RA, Tzizik D. Update on surgical site infections: the new CDC guidelines. JAAPA 2018; 31 (04) 52-54
- 9 Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010; 23 (03) 467-492
- 10 Kimberlin DW. Red Book: 2018–2021 report of the committee on infectious diseases. American Academy of Pediatrics; 2018
- 11 Haque M, McKimm J, Godman B, Abu Bakar M, Sartelli M. Initiatives to reduce postoperative surgical site infections of the head and neck cancer surgery with a special emphasis on developing countries. Expert Rev Anticancer Ther 2019; 19 (01) 81-92
- 12 Sattar F, Sattar Z, Zaman M, Akbar S. Frequency of post-operative surgical site infections in a Tertiary care hospital in Abbottabad, Pakistan. Cureus 2019; 11 (03) e4243
- 13 Sáenz A, Badaloni E, Grijalba M, Villalonga JF, Argañaraz R, Mantese B. Risk factors for surgical site infection in pediatric posterior fossa tumors. Childs Nerv Syst 2021; 37 (10) 3049-3056
- 14 Sneh-Arbib O, Shiferstein A, Dagan N. et al. Surgical site infections following craniotomy focusing on possible post-operative acquisition of infection: prospective cohort study. Eur J Clin Microbiol Infect Dis 2013; 32 (12) 1511-1516
- 15 Lee RP, Venable GT, Vaughn BN, Lillard JC, Oravec CS, Klimo Jr P. The impact of a pediatric shunt surgery checklist on infection rate at a single institution. Neurosurgery 2018; 83 (03) 508-520
- 16 Boethun A, Vissing NH, Mathiasen R, Skjøth-Rasmussen J, Foss-Skiftesvik J. CNS infection in children with brain tumors: adding ventriculostomy to brain tumor resection increases risk more than 20-fold. Childs Nerv Syst 2023; 39 (02) 387-394
- 17 Alther B, Mylius V, Weller M, Gantenbein A. From first symptoms to diagnosis: Initial clinical presentation of primary brain tumors. Clin Transl Neusci 2020; 4 (02) 17 . Doi: 2514183X20968368
- 18 Roth J, Constantini S. Hydrocephalus and brain tumors. Cerebrospinal Fluid Disorders SpringerLink; 2019
- 19 Paoli CJ, Reynolds MA, Sinha M, Gitlin M, Crouser E. Epidemiology and costs of sepsis in the United States—an analysis based on timing of diagnosis and severity level. Crit Care Med 2018; 46 (12) 1889-1897
- 20 Allegranzi B, Bischoff P, de Jonge S. et al; WHO Guidelines Development Group. New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis 2016; 16 (12) e276-e287
Address for correspondence
Publication History
Article published online:
15 April 2024
© 2024. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Hossain MJ, Xiao W, Tayeb M, Khan S. Epidemiology and prognostic factors of pediatric brain tumor survival in the US: evidence from four decades of population data. Cancer Epidemiol 2021; 72: 101942
- 2 Bhakta N, Force LM, Allemani C. et al. Childhood cancer burden: a review of global estimates. Lancet Oncol 2019; 20 (01) e42-e53
- 3 Udaka YT, Packer RJ. Packer RJJNc. Pediatric brain tumors. Neurol Clin 2018; 36 (03) 533-556
- 4 Bathla G, Policeni B, Hansen MR, Berbaum K. Calculating the tumor volumes in vestibular schwannomas: are the ABC/2 and volumetric methods comparable?. Otol Neurotol 2017; 38 (06) 889-894
- 5 Louis DN, Perry A, Wesseling P. et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-oncol 2021; 23 (08) 1231-1251
- 6 Palombi L, Marchetti P, Salvati M, Osti MF, Frati L, Frati A. Interventions to reduce neurological symptoms in patients with GBM receiving radiotherapy: from theory to clinical practice. Anticancer Res 2018; 38 (04) 2423-2427
- 7 Karschnia P, Vogelbaum MA, van den Bent M. et al. Evidence-based recommendations on categories for extent of resection in diffuse glioma. Eur J Cancer 2021; 149: 23-33
- 8 Borchardt RA, Tzizik D. Update on surgical site infections: the new CDC guidelines. JAAPA 2018; 31 (04) 52-54
- 9 Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010; 23 (03) 467-492
- 10 Kimberlin DW. Red Book: 2018–2021 report of the committee on infectious diseases. American Academy of Pediatrics; 2018
- 11 Haque M, McKimm J, Godman B, Abu Bakar M, Sartelli M. Initiatives to reduce postoperative surgical site infections of the head and neck cancer surgery with a special emphasis on developing countries. Expert Rev Anticancer Ther 2019; 19 (01) 81-92
- 12 Sattar F, Sattar Z, Zaman M, Akbar S. Frequency of post-operative surgical site infections in a Tertiary care hospital in Abbottabad, Pakistan. Cureus 2019; 11 (03) e4243
- 13 Sáenz A, Badaloni E, Grijalba M, Villalonga JF, Argañaraz R, Mantese B. Risk factors for surgical site infection in pediatric posterior fossa tumors. Childs Nerv Syst 2021; 37 (10) 3049-3056
- 14 Sneh-Arbib O, Shiferstein A, Dagan N. et al. Surgical site infections following craniotomy focusing on possible post-operative acquisition of infection: prospective cohort study. Eur J Clin Microbiol Infect Dis 2013; 32 (12) 1511-1516
- 15 Lee RP, Venable GT, Vaughn BN, Lillard JC, Oravec CS, Klimo Jr P. The impact of a pediatric shunt surgery checklist on infection rate at a single institution. Neurosurgery 2018; 83 (03) 508-520
- 16 Boethun A, Vissing NH, Mathiasen R, Skjøth-Rasmussen J, Foss-Skiftesvik J. CNS infection in children with brain tumors: adding ventriculostomy to brain tumor resection increases risk more than 20-fold. Childs Nerv Syst 2023; 39 (02) 387-394
- 17 Alther B, Mylius V, Weller M, Gantenbein A. From first symptoms to diagnosis: Initial clinical presentation of primary brain tumors. Clin Transl Neusci 2020; 4 (02) 17 . Doi: 2514183X20968368
- 18 Roth J, Constantini S. Hydrocephalus and brain tumors. Cerebrospinal Fluid Disorders SpringerLink; 2019
- 19 Paoli CJ, Reynolds MA, Sinha M, Gitlin M, Crouser E. Epidemiology and costs of sepsis in the United States—an analysis based on timing of diagnosis and severity level. Crit Care Med 2018; 46 (12) 1889-1897
- 20 Allegranzi B, Bischoff P, de Jonge S. et al; WHO Guidelines Development Group. New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis 2016; 16 (12) e276-e287













