Whether 3.0 g cefuroxime prophylaxis before cardiac surgery diminished postoperative pneumonia and persistent fever compared with 1.5 g: a nested case-control study

doi:10.21203/rs.3.rs-4727283/v1

Objectives

Whether 3.0 g CXM prophylaxis before cardiac surgery can effectively avoid POP and persistent POFcompared with 1.5 g is debatable, which needs to be confirmed by evidence medical research.

Methods

A total of 301 patients who underwent CXM prophylaxis before cardiac surgery from Jan 2023 to Dec 2023 at the First Affiliated Hospital of Nanjing Medical University were incorporated in a nested case-control study. The patients were divided into the 1.5 g (n=170) and 3.0 g (n=131) groups according to the dosage of prophylactic CXM. Outcomes included POP and persistent POF. Risk andstratification analysis was performed for the effect andmodification of different doses of CXM on outcomes.

Results

The incidence of persistent POF in 1.5 g group (52, 30.59%) was lower than that in 3.0 g group (67, 51.15%) unadjusted (OR=2.38, 95%CI:1.48~3.81, P<0.001) or adjusted (OR=2.38, 95%CI:1.36~4.14, P=0.002) for the confounding variables. There was no significant difference in POP between the two groups unadjusted (OR=1.26, 95%CI:0.62~2.55, P=0.522) or adjusted (OR=1.03., 95%CI:0.48~2.20, P=0.945) for the confounding variables. The results of stratification analysis defined that two different dosages of prophylactic CXM didn’t generate effect modification on the risk factors of persistent POF.

Conclusions

3.0 g CXM prophylaxis before cardiac surgery didn’t decrease the incidence of POP but increased the risk of persistent POF compared with 1.5 g. Given the facts, this study may point the solution of CXM preoperative prophylaxis for cardiac surgery.

nested case-control study

1.5 g or 3.0 g cefuroxime preoperative prophylaxis

cardiac surgery

postoperative pneumonia

persistent postoperative fever

Cardiac surgery is a complex, technical and demanding interventional therapy for patients with cardiac diseases. Despite advances in surgical techniques and postoperative care, the risk of nosocomial infection and persistent postoperative fever(POF) remain great challenges among patients who undergo cardiac surgery. The incidence of nosocomial infection was described with 10.1%^[1]up to 22.6%^[2], among which postoperative pneumonia(POP) ranked first with the incidence of 8.8%^[3] up to 20.9%^[4]. POP has proved to complicate treatment, prolong hospital stay, and increase clinical burdens and mortality rate^[5]. POF is the most common complications and may occur up to 70% of patients undergoing cardiac surgery^[6]. POF often leads to unnecessary extensive laboratory work-ups and antimicrobial therapies. The atypical presentations often cause a delayed diagnosis and an improper treatment with an increased morbidity rate^[7]. Therefore, more attentions should be paid to decrease the morbidity of POP and persistent POF in cardiac surgery.

Routine administration of perioperative antibiotic prophylaxis(AP) is well accepted due to the severity of infection in cardiac surgeries^[8]. Prior studies have revealed AP reduces the incidence of POP, bloodstream and surgical site infection(SSI)^[9-11]. The German Paul-Ehrlich-Gesellschaft e.V. (PEG) recommended second-generation cephalosporin as first-line AP in patients undergoing cardiac surgery^[12]. The Chinese Guidelines for Clinical Use of Antibiotics(2015 edition)^[13]recommended 1.5 g CXM as preferred AP regimen in these patients without considering the function of liver and kidney. However, a pharmacokinetic evaluation study^[14]of CXM revealed that a standard dosing regimen of 1.5 g preoperatively to prevent staphylococcal infections appears to be effective. In contrast, if E. coli is relevant in surgeries, this dosing regimen appears insufficient. Another study^[15] showed patients with body weight > 100 kg or age < 60 years were more likely to have unbound plasma concentrations below the target range. In consideration of maintaining the serum and tissue concentrations of CXM with a short half-life^[16], and the severity of infection after cardiac surgeries, some clinicians tented to select 3.0 g dosing regimen preoperatively. Therefore, further research is warranted to clarify whether 3.0 g CXM prophylaxis before cardiac surgery can effectively diminish POP and persistent POF compared with 1.5 g.

In this study, the effect of 1.5 g and 3.0 g CXM prophylaxis preoperatively on the incidence of POP and persistent POF were investigated among patients undergoing cardiac surgery.

Study subjects

Patients undergoing cardiac surgery from Jan 2023 to Dec 2023 at the First Affiliated Hospital of Nanjing Medical University were involved in a nested case-control study. Inclusion and exclusion criteria of the study was described as follow. Patients who underwent CXM prophylaxis before cardiac surgery were enrolled in this study apart from patients with a preoperative fever or infection, or undergoing emergency surgery. According to the sample size estimating calculation formula N=Z_α/₂²×P₀(1-P₀)/δ² with α and δ were 0.05, and the positive rate (P₀) of POF was 70% reported by Keijmel SP et al^[6], 322 cases should be involved. Finally, a total of 301 patients were admitted into the study according to the eligibility criteria. Participants were divided into the 1.5 g (n=170) and 3.0 g (n=131) group based on the dosage of CXM prophylaxis before operation. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University.

Data collection

The demographic data of participants, including baseline characteristics [age, smoking and drinking history, Body Mass Index(BMI), Controlling Nutritional Status(CONUT) grade], preoperative information [length of hospital stay, Platelets-Lymphocyte ratio(PLR), Neutrophil-Lymphocyte ratio(NLR), Monocyte-Lymphocyte ratio(MLR), Systemic Inflammatory Index(SII)], Surgical variables [American Society of Anesthesiology(ASA) score, National Nosocomial Infections Surveillance(NNIS) index,Cardiopulmonary bypass(CPB), red blood cell(RBC), washed RBC or platelet(PLT) transfusion, surgical time, intraoperative blood loss or transfusion], and antibiotic (preoperative AP, length of preoperative AP, intraoperative redosing, AP within 48 h postoperatively) were collected by the Xinglin Real-Time Nosocomial Infection System and Intelligent Integrated Health(iih) platform.

Outcomes

Outcomes included POP and persistent POF. POP were diagnosed referring to the Diagnostic Criteria of Nosocomial Infection published by the Ministry of Health in 2001. To identify with absorption and reaction fever, POF in this study was defined as persistent fever(auxillary temperature≥38℃) ≥3 d. According to different outcomes, participants were allocated into POP group (n=35) and non-POP group(n=266), or POF group(n=119) and non-POF group(n=182).

Statistical analysis

Data were summarized with Excel 2017 and statistical analysis was performed by R 4.3.3. Continuous variables were summarized as mean±standard deviation(SD) and compared with t-test if data conform with normality and homogeneity of variance simultaneously. Otherwise, these variables were summarized as median±interquartile and compared with Mann-Whitney U test. Categorical data were described as frequencies (percentages), and compared with Pearson χ² test . Univariate and multivariate logistic regression model was used to analyze the risk factors for POP and persistent POF. Risk risks with P value less than 0.05 in univariate analysis was incorporated into the further multivariate analysis. The effect of different dosages CXM prophylaxis was determined by adjusting the risk factors assessed from multivariate logistic regression model. Stratification analysis was conducted to examine whether different dosages CXM prophylaxis generate effect modification on risk factor of POP or persistent POF. The effect of risk factors on the outcome was presented by odds ratio(OR) and its 95% confidence interval(CI). P value less than 0.05 was considered as statistical difference.

Baseline characteristics, preoperative information, surgical variables, antibiotic and outcomes

Baseline characteristics

No significant differences were found in age, smoking, drinking, BMI, CONUT grade between 1.5 g and 3.0 g groups(Table 1).

Preoperative information

There was no significant difference in length of hospital stay, PLR, NLR, MLR, SII between 1.5 g and 3.0 g groups(Table 1).

Surgical variables

The percentage of cardiopulmonary bypass in 1.5 g group was higher than 3.0 g group (P=0.020), while the rate of washed RBC transfusion and volume of intraoperative blood transfusion in 1.5g group was lower than 3.0 g group (P=0.016 and 0.026). No significant differences were found in other surgical variables (ASA score, NNIS index, RBC transfusion, PLT transfusion, surgical time, intraoperative blood loss) between the two groups(Table 1).

Antibiotic

The percentage of AP within 48 h postoperatively in 1.5 g group was higher than 3.0 g group (P=0.023). There was no significant difference in length of AP before operation, intraoperative redosing(Table 1).

Outcomes

The overall incidence of POP and persistent POF was 11.63% and 39.53%, respectively. The incidence of persistent POF in 3.0 g group (30.59%) was higher than 1.5 g group (51.15%)(P<0.001). There was no significant difference in POP between the two groups (10.59% and 12.98%)(Table 1).

Risk factors analysis

In accordance with the consequence of univariate logistic regression analysis, the risk of POP increased with age (OR=1.05, 95%CI:1.00~1.09, P=0.031),smoking history (OR=2.81, 95%CI:1.35~5.84, P=0.006), length of hospital stay before operation (OR=1.07, 95%CI:1.05~1.10, P<0.001), CONUT grade [light (OR=3.97, 95%CI:1.65~9.54, P=0.002), medium and severe (OR=4.22, 95%CI:1.12~15.86, P=0.033)], ASA score (4 and 5)(OR=2.69, 95%CI:1.13~6.39, P=0.025), surgical time (OR=1.65, 95%CI:1.30~2.07, P<0.001) and the risk of persistent POF increased with age (OR=1.03, 95%CI:1.00~1.05, P=0.031), smoking (OR=2.66, 95%CI:1.55~4.59, P<0.001) and drinking (OR=1.85, 95%CI:1.04~3.30, P=0.036) history, length of hospital stay before operation (OR=1.21, 95%CI:1.15~1.26, P<0.001), NLR (OR=1.32, 95%CI:1.10~1.58, P=0.002), MLR (OR=14.80, 95%CI:3.10~70.70, P=0.001), CONUT grade [light (OR=2.87, 95%CI:1.73~4.77, P<0.001), medium and severe (OR=8.00, 95%CI:2.90~22.04, P<0.001)], ASA score (4 and 5) (OR=2.38, 95%CI:1.44~3.93, P<0.001), CPB (OR=1.90, 95%CI:1.10~3.31, P=0.022), washed RBC (OR=2.32, 95%CI:1.44~3.74, P=0.001) and PLT (OR=2.34, 95%CI:1.46~3.75, P<0.001) transfusion, surgical time (OR=1.59, 95%CI:1.32~1.90, P<0.001), and no AP within 48 h postoperatively (OR=1.76, 95%CI:1.01~3.07, P<0.046)(Table 2).

The significant variables in univariate analysis was screened by a stepwise multivariate logistic regression. The multivariate analysis revealed that increased age (OR=1.06, 95%CI:1.01~1.10, P=0.018) and surgical time (OR=1.69, 95%CI:1.33~2.15, P<0.001), history of smoking (OR=3.05, 95%CI:1.40~6.67, P=0.005) was related to higher risk of POP while increased length of hospital stay before operation (OR=1.06, 95%CI:1.01~1.11, P=0.022) and surgical time (OR=1.52, 95%CI:1.25~1.85, P<0.001), higher MLR (OR=6.55, 95%CI:1.41~30.47, P=0.017) and CONUT grade [light (OR=1.90, 95%CI:1.07~3.38, P=0.028), medium and severe (OR=4.27, 95%CI:1.28~14.21, P=0.018)], smoking history (OR=2.72, 95%CI:1.47~5.06, P=0.002), washed RBC transfusion (OR=1.69, 95%CI:1.16~2.46, P=0.007) was positive correlated with risk of persistent POF(Table 3).

1.5 g or 3.0 g CXM prophylaxis before operation and POP and persistent POF

Correlation analysis demonstrated the risk of postoperative persistent POF in patients with 3.0 g CXM prophylaxis before operation is higher than those with 1.5 g CXM unadjusted (OR=2.38, 95%CI:1.48~3.81, P<0.001) or adjusted (OR=2.38, 95%CI:1.36~4.14, P=0.002) for the confounding effect of smoking history, length of hospital stay before operation, MLR, CONUT grades, washed RBC transfusion and surgical time. There was no significant different in POP between the two group unadjusted (OR=1.26, 95%CI:0.62~2.55, P=0.522) or adjusted (OR=1.03., 95%CI:0.48~2.20, P=0.945) for the confounding variables(Table 4).

Stratification analysis

Stratification analysis showed that there was no significant difference in the effect of smoking history, length of hospital stay before operation, MLR, CONUT grade, washed RBC transfusion, surgical time between 1.5 g and 3.0 g group(Table 5). The results defined that the two different dosages CXM prophylaxis didn’t generate effect modification on risk factor of postoperative persistent POF.

This study was conducted to identify whether 3.0 g CXM prophylaxis preoperatively be has a significant advantage over 1.5 g and provide basic data for establishing antibiotic use guidelines for patients undergoing cardiac surgery. The results demonstrated that 3.0 g CXM prophylaxis preoperatively did not significantly decreased the prevalence of POP and served only to increase the risk of persistent POF compared with 1.5 g among patients undergoing cardiac surgery.

In this study, 11.63% patients developed pneumonia after cardiac surgery. The incidence level was similar to the results(9.6%) in a prospective cohort study^[17] of a large Grade-A tertiary hospital. POP is most prevalent of all nosocomial infections in patients who underwent cardiac surgery^[18]. Age, smoking history, duration of mechanical ventilation (MV) are well-known risk factors that affect POP^[3,19]. Risk factors analysis in this study verified age,smoking history and surgical time increased the probability of POP. Regrettably, the clinical data of postoperative MV couldn’t be involved in risk factors analysis because of data loss.

The incidence of persistent POF among patients undergoing cardiac surgery was 39.53% in the study. The incidence level was similar to the result(38%) in a review^[20]. POF is a common occurrence after cardiac surgery, only a small percentage of which was due to infections^[21]. Most POF is benign and self-limiting resulting from release of inflammation cytokines caused by surgical trauma and blood directly contacting with the tubes and oxygenator surfaces during CPB circuit^[22]. The presence of POF frequently triggers a battery of diagnostic tests and produces misleading in empiric antibiotics without clear infection sources. Excessive use of antibiotics can lead to the production of drug-resistant bacteria^[23]. Previous studies^[24-25] declared diabetes, lesion size, operation time, high C-reactive protein and placement of a urinary catheter were risk factors of POF. This study creatively involved a series of inflammatory composite index including PLR,NLR, MLR, SII in risk factors analysis and identified prolonged hospital stay before operation and surgical time , higher MLR and CONUT grade, history of smoking, washed RBC transfusion increased the risk of persistent POF. MLR as a marker, was strongly correlated with POF after cardiac surgery. A prospective study^[26] in 2022 confirmed high level of MLR was clinically significantly with increased prevalence of postoperative delirium among patients undergoing cardiac surgery. Another cohort study^[27] in 2021 revealed high level of MLR was a reliable predictive indicator of patients with mortality risk after cardiac surgery. However, the clinical data of urinary and venous catheter was not included in risk factors analysis.

A preventive anti-infectious strategy is well-known to reduce the postoperative risk of nosocomial infections and to avoid prolonged antibiotic exposure. Current guidelines in China recommends 1.5 g CXM as preferred AP regimen in cardiac surgery. The recommended proposal is similar to the American Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery^[28]. Christer Rimmler^[29] reported that dosing recommendations for CXM as perioperative AP in cardiac surgery are sufficient to reach plasma unbound concentration to cover S. aureus during the operation. However, J Lanoiselée et al^[30] stated common dosing regimens of 1.5 g CXM recommended by US and European guidelines did not sustain therapeutic concentrations throughout cardiac surgery and proposed an optimized dosing regimen according to the population analysis of CXM pharmacokinetics. Another study showed a standard dosing regimen of 1.5 g CXM preoperatively seemed to ineffective in preventing E. coli by pharmacokinetic analysis^[14]. There are inconsistent with the guideline recommendations and study results of dosage in CXM prophylaxis preoperatively for cardiac surgery. Whether a higher dosing regimen prophylaxis preoperatively is superior to guideline recommendation has not been reported so far. In our study, 3.0 g CXM prophylaxis preoperatively did not significantly decreased the prevalence of POP, but increased the risk of persistent POF compared with 1.5 g. The results support the Chinese and American guidelines. Besides, most guidelines suggest not to preventive use of antibiotics postoperatively, if necessary the duration of AP after clean-contaminated surgery and contaminated surgery should not exceed 24 h and might extend to 48 h for contaminated surgery. However, a nationwide questionnaire from German heart surgery centers showed AP was extensive after cardiac surgery, with the duration strategy varying wildly^[31]. This study failed to determine a significant difference in AP within 48 h postoperatively by multivariate analysis, indicating little importance and necessity of postoperative AP. The result is consistent with Chinese and American guidelines.

The study may provide basic data for establishing antibiotic use guidelines for patients undergoing cardiac surgery by a nested case-control study. Ultimately, the prospective study is conform to temporal logic in causal inference. Moreover, the whole population who underwent CXM prophylaxis before cardiac surgery was included in this study. Nevertheless, the present study has some disadvantages. First, all results were derived from a single center and the sample size was slightly lower than statistical requirement. Second, the clinical data of relevant factors, including interventional therapy after surgery couldn’t be involved in risk factors analysis. Finally, the effect of intraoperative AP redosing wasn’t verified with a statistical difference. Afterwards, the results need to be validated by a cohort study with comprehensive data and rigorous quality control.

On the basis of the international literature, the different guidelines and the results obtained in this nested case-control study, increasing the dosage of preoperative CXM prophylaxis from 1.5 g to 3.0 g in patients undergoing cardiac surgery does not diminish the prevalence of POP, but contributes to increased risk of persistent POF. It may reduce antibiotic resistant,healthcare costs and even provide a standardized strategy of AP management in cardiac surgery.

Acknowledgements:

The authors are grateful to the clinical medical institution members, nurses, and physicians to perform this study.

Author contributions

Conception and design: FZ and JY. Provision of study materials or patients: WC, FZ, ZG. Collection and assembly of data: JY, WC, ZG and FZ. Data analysis and interpretation: JY, QM and XG. All authors read and approved the final manuscript.

Fundings

This study was supported by the Young Talent Development Program of Changzhou Health Commission (CZQM2023021), Health Young Scientific and Technological Talent Development Program of Changzhou Medical Development Center and Changzhou Medical Association (lcyx2023010), the third Outstanding Young and Middle-aged Talents Training Program of Jiangsu Provincial People’s Hospital (YNRCQN0314), Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University (PY2022017), Jiangsu Province Hospital Management Innovation Research Project (JSYGY-3-2023-559), Project of Chinese Hospital Reform and Development Institute, Nanjing University (NDYG2023039).

Availability of data and materials

The datasets of the study are available in this published article.

Ethics approval and consent to participate

This study has been approved by the ethical committee of The First Affiliated Hospital of Nanjing Medical University review board.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Table1 Characteristic and outcomes of patients categorized by 1.5 g and 3.0 g CXM prophylaxis before operation

Characteristic	1.5 g CXM prophylaxis before operation (n=170)	3.0 g CXM prophylaxis before operation (n=131)	Statistical value	P value
Baseline characteristics
Age(y)	61.58±10.10	61.79±11.21	0.864	0.864
Smoking history	36(21.18)	35(26.72)	1.260	0.262
Drinking history	28(16.47)	30(22.90)	1.967	0.161
BMI			3.023	0.388
＜18.5	3(1.77)	5(3.82)
18.5≤BMI＜24.9	105(61.76)	88(67.18)
25.0≤BMI＜29.9	57(33.53)	36(27.48)
＞30.0	5(2.94)	2(1.52)
CONUT grade			0.208	0.901
Normal	81(47.65)	59(45.04)
Light	77(45.29)	62(47.33)
Medium and Severe	12(7.06)	10(7.63)
Preoperative information
Length of hospital stay before operation(d)	24.39±16.85	24.83±15.67	0.230	0.818
PLR	125.51±54.98	123.76±54.47	0.275	0.784
NLR	2.59±2.55	2.56±1.66	0.073	0.942
MLR	0.33±0.21	0.34±0.17	0.378	0.706
SII	477.34±452.13	461.59±394.90	0.326	0.745
Surgical variables
ASA score			0.751	0.386
1~3	68(40.00)	46(35.11)
4~5	102(60.00)	85(64.89)
NNIS index			1.407	0.236
1	20(11.76)	10
2	150(88.24)	121
CPB	116(68.24)	105(80.15)	5.385	0.020
RBC transfusion	51(30.00)	45(34.35)	0.645	0.422
Washed RBC transfusion	80(47.06)	80(61.07)	5.832	0.016
PLT transfusion	81(47.65)	58(44.27)	0.339	0.561
Surgical time(h)	4.63±1.55	4.95±1.53	1.800	0.073
Intraoperative blood loss(mL)	400	500	0.284	0.776
Intraoperative blood transfusion(mL)	1162.5	2300	2.230	0.026
Antibiotic
Length of AP before perioperation(d)	1.00	1.00	1.764	0.078
Intraoperative redosing			1.381	0.501
Required but no redosing	30(17.65)	22(16.79)
Required and redosing	122(71.76)	100(76.34)
Not required	18(10.59)	9(6.87)
AP within 48 h postoperatively	52(30.59)	25(19.08)	5.144	0.023
Outcomes
POP	18(10.59)	17(12.98)	0.411	0.522
Persistent POF	52(30.59)	67(51.15)	13.079	＜0.001

CXM, cefuroxime; PLR, Platelets-Lymphocyte ratio; NLR, Neutrophil-Lymphocyte ratio; MLR, Monocyte-Lymphocyte ratio; SII, Systemic Inflammatory Index; CONUT, Controlling Nutritional Status; BMI, Body Mass Index; ASA, American Society of Anesthesiology; NNIS, National Nosocomial Infections Surveillance; CPB, Cardiopulmonary bypass; RBC, red blood cell; PLT, platelet; AP, antibiotic prophylaxis; POP, postoperative pneumonia; POF, postoperative fever.

Table 2 Univariate logistic regression for the suspected influence factors with POP and Persistent POF

Exposure	POP				Persistent POF
Exposure	Case	Control	OR（95%CI）	P value	Case	Control	OR（95%CI）	P value
Baseline characteristics
Age(y)	65.31±9.85	61.20±10.59	1.05（1.00,1.09）	0.031	63.32±9.78	60.60±10.96	1.03（1.00,1.05）	0.031
Smoking hostory
No	20(57.14)	210(78.95)	1	0.006	78(65.55)	152(83.52)	1	＜0.001
Yes	15(42.86)	56(21.05)	2.81(1.35,5.84)	0.006	41(34.45)	30(16.48)	2.66(1.55,4.59)	＜0.001
Drinking hostory
No	26(74.29)	217(81.58)	1	0.307	89(74.79)	154(84.62)	1	0.036
Yes	9(25.71)	49(18.42)	1.53(0.68,3.48)	0.307	30(25.21)	28(15.38)	1.85(1.04,3.30)	0.036
BMI
＜18.5	2(5.71)	6(2.26)	1		5(4.20)	3(1.65)	1
18.5≤BMI＜24.9	23(65.72)	170(63.91)	0.41(0.08,2.13)	0.287	84(70.59)	109(59.89)	0.46(0.11,1.99)	0.300
25.0≤BMI＜29.9	10(28.57)	83(31.20)	0.36(0.06,2.04)	0.249	26(21.85)	67(36.81)	0.23(0.05,1.04)	0.057
＞30.0	0(0)	7(2.63)	Incalculable		4(3.36)	3(1.65)	0.80(0.10,6.35)	0.833
CONUT grade
Normal	7(20.00)	133(50.00)	1		35(29.41)	105(57.69)	1
Light	24(68.57)	115(43.23)	3.97(1.65,9.54)	0.002	68(57.14)	71(39.01)	2.87(1.73,4.77)	＜0.001
Medium and Severe	4(11.43)	18(6.77)	4.22(1.12,15.86)	0.033	16(13.45)	6(3.30)	8.00(2.90,22.04)	＜0.001
Preoperative information
Length of hospital stay before operation(d)	46.00±26.63	21.77±11.92	1.07(1.05,1.10)	＜0.001	35.75±20.40	17.29±5.90	1.21(1.15,1.26)	＜0.001
PLR	126.20±58.77	124.55±54.23	1.00(0.99,1.01)	0.867	129.50±64.54	121.64±47.06	1.00(1.00,1.01)	0.224
NLR	2.73±1.50	2.55±2.28	1.03(0.90,1.18)	0.649	3.063±3.16	2.253±1.12	1.32(1.10,1.58)	0.002
MLR	0.37±0.15	0.33±0.19	2.76(0.62,12.27)	0.181	0.38±0.25	0.30±0.13	14.80(3.10,70.70)	0.001
SII	460.94±340.84	471.74±434.21	1.00(1.00,1.00)	0.887	534.17±590.96	428.84±256.50	1.00(1.00,1.00)	0.054
Surgical variables
ASA score
1~3	7(20.00)	107(40.22)	1	0.025	31(26.05)	83(45.60)	1	＜0.001
4~5	28(80.00)	159(59.78)	2.69(1.13,6.39)	0.025	88(73.95)	99(54.40)	2.38(1.44,3.93)	＜0.001
NNIS index
1	2(5.71)	28(10.53)	1	0.380	9(7.56)	21(11.54)	1	0.264
2	33(94.29)	238(89.47)	1.94(0.44,8.53)	0.380	110(92.43)	161(88.46)	1.59(0.70,3.61)	0.264
CPB
No	5(14.29)	75(28.20)	1	0.088	23(19.33)	57(31.32)	1	0.022
Yes	30(85.71)	191(71.80)	2.36(0.88,6.30)	0.088	96(80.67)	125(68.68)	1.90(1.10,3.31)	0.022
RBC transfusion
No	24(68.57)	181(68.05)	1	0.950	75(63.02)	130(71.43)	1	0.127
Yes	11(31.43)	85(31.95)	0.98(0.46,2.08)	0.950	44(36.98)	52(28.57)	1.47(0.90,2.40)	0.127
Washed RBC transfusion
No	12(34.29)	129(48.50)	1	0.117	41(34.45)	100(54.95)	1	0.001
Yes	23(65.71)	137(51.50)	1.80(0.86,3.78)	0.117	78(65.55)	82(45.05)	2.32(1.44,3.74)	0.001
PLT transfusion
No	14(40.00)	148(55.64)	1	0.085	49(41.18)	113(62.09)	1	＜0.001
Yes	21(60.00)	118(44.36)	1.88(0.92,3.86)	0.085	70(58.82)	69(37.91)	2.34(1.46,3.75)	＜0.001
Surgical time(h)	5.91±1.81	4.62±1.44	1.65(1.30,2.07)	＜0.001	5.35±1.64	4.38±1.35	1.59(1.32,1.90)	＜0.001
Intraoperative blood loss(mL)	50	400	1.00(1.00,1.00)	0.734	50	500	1.00(1.00,1.00)	0.352
Intraoperative blood transfusion(mL)	1000	1400	1.00(1.00,1.00)	0.332	700	1600	1.00(1.00,1.00)	0.608
Antibiotic
Length of AP before perioperation(d)	1.74±2.58	1.95±1.92	0.94(0.76,1.16)	0.564	1.68±2.00	2.09±1.99	0.89(0.77,1.02)	0.095
Intraoperative redosing
Required but no redosing	9(25.71)	43(16.17)	1		23(19.33)	29(15.93)	1
Required and redosing	25(71.43)	197(74.06)	0.61(0.26,1.39)	0.238	89(74.79)	133(73.08)	0.84(0.46,1.55)	0.585
Not required	1(2.86)	26(9.77)	0.18(0.02,1.53)	0.118	7(5.88)	20(10.99)	0.44(0.16,1.22)	0.116
AP within 48 h postoperatively
No	29(82.86)	195(73.31)	1	0.229	96(80.67)	128(70.33)	1	0.046
Yes	6(17.14)	71(26.69)	0.57(0.23,1.43)	0.229	23(19.33)	54(29.67)	0.58(0.33,0.99)	0.046

CXM, cefuroxime; PLR, Platelets-Lymphocyte ratio; NLR, Neutrophil-Lymphocyte ratio; MLR, Monocyte-Lymphocyte ratio; SII, Systemic Inflammatory Index; CONUT, Controlling Nutritional Status; BMI, Body Mass Index; ASA, American Society of Anesthesiology; NNIS, National Nosocomial Infections Surveillance; CPB, Cardiopulmonary bypass; RBC, red blood cell; PLT, platelet; AP, antibiotic prophylaxis; POP, postoperative pneumonia; POF, postoperative fever；OR, odds ratio; CI, confidence interval.

Table 3 Multivariate logistic regression for risk factors with POP and persistent POF

Exposure	β value	SE	Wald χ^２	OR（95%CI）	P value
POP
Age(y)	0.054	0.023	5.641	1.06(1.01,1.10)	0.018
Smoking history	1.116	0.399	7.815	3.05(1.40,6.67)	0.005
Surgical time(h)	0.527	0.123	18.425	1.69(1.33,2.15)	＜0.001
Persistent POF
Smoking history	1.002	0.316	10.030	2.72(1.47,5.06)	0.002
Length of hospital stay before operation(d)	0.057	0.025	5.255	1.06(1.01,1.11)	0.022
MLR	1.879	0.784	5.742	6.55(1.41,30.47)	0.017
CONUT grade Light	0.644	0.293	4.844	1.90(1.07,3.38)	0.028
Medium and Severe	1.451	0.613	5.599	4.27(1.28,14.21)	0.018
Washed RBC transfusion	0.523	0.193	7.346	1.69(1.16,2.46)	0.007
Surgical time(h)	0.417	0.100	17.212	1.52(1.25,1.85)	＜0.001

MLR, Monocyte-Lymphocyte ratio; CONUT, Controlling Nutritional Status; RBC, red blood cell; POP,

postoperative pneumonia; POF, postoperative fever; OR, odds ratio; CI, confidence interval.

Table 4 Associations of 1.5 g and 3.0 g CXM prophylaxis before operation with POP and persistent POF among patients undergoing cardiac surgery

Exposure	Case	Control	Crude OR（95%CI）	Crude P	Adjusted OR (95%CI)	Adjusted P

POP
1.5g CXM prophylaxis before operation	18(51.43)	152(57.14)	1.26(0.62,2.55)	0.522	1.03(0.48,2.20) ^a	0.945 ^a
3.0g CXM prophylaxis before operation	17(48.57)	114(42.86)
Persistent POF
1.5g CXM prophylaxis before operation	52(43.70)	118(64.84)	2.38(1.48,3.81)	＜0.001	2.38(1.36,4.14) ^b	0.002 ^b
3.0g CXM prophylaxis before operation	67(56.30)	64(35.16)

^aAdjustment for age, smoking history and surgical time.

^b Adjustment for smoking history, length of hospital stay before operation, MLR, CONUT grade, washed WBC transfusion, surgical time.

CXM, cefuroxime; MLR, Monocyte-Lymphocyte ratio; CONUT, Controlling Nutritional Status; RBC, red blood cell; POP, postoperative pneumonia; POF,

postoperative fever; OR, odds ratio; CI, confidence interval.

Table 5 Stratification analysis of risk factors with persistent POF in 1.5 g subgroup and 3.0 g subgroup

Exposure	1.5g CXB prophylaxis before operation	3.0g CXB prophylaxis before operation	P for heterogeneity
Exposure	Adjusted OR (95%CI) ^b	Adjusted OR (95%CI) ^b	P for heterogeneity
Smoking history	3.58(1.41,9.06)	2.44(0.97,6.14)	0.567
Length of hospital stay before operation(d)	1.07(1.01,1.14)	1.08(0.95,1.22)	0.938
MLR	15.02(1.99,113.26)	3.37(0.17,67.51)	0.417
CONUT grade Light	1.57(0.66,3.70)	2.31(0.98,5.43)	0.532
Medium and Severe	2.84(0.54,14.96)	9.30(0.94,91.92)	0.411
Washed RBC transfusion	2.40(1.35,4.27)	1.11(0.64,1.92)	0.056
Surgical time(h)	1.71(1.28,2.29)	1.34(1.00,1.79)	0.240

^bAdjustment for smoking history, length of hospital stay before operation, MLR, CONUT grade, washed WBC transfusion and surgical time.

CXM, cefuroxime; MLR, Monocyte-Lymphocyte ratio; CONUT, Controlling Nutritional Status; RBC, red blood cell; POP, postoperative pneumonia; POF,

postoperative fever; OR, odds ratio; CI, confidence interval.

No competing interests reported.

rawdata.xls

Whether 3.0 g cefuroxime prophylaxis before cardiac surgery diminished postoperative pneumonia and persistent fever compared with 1.5 g: a nested case-control study

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Abstract

Introduction

Participants and methods

Results

Discussion

Conclusions

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

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