Efficacy of single antibiotic therapy versus antibiotic combination in implant-free staphylococcal spinal infections: a retrospective observational study

doi:10.21203/rs.3.rs-3017669/v1

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Research Article

Efficacy of single antibiotic therapy versus antibiotic combination in implant-free staphylococcal spinal infections: a retrospective observational study

https://doi.org/10.21203/rs.3.rs-3017669/v1

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Journal Publication

published 08 Jan, 2024

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Background

Post-surgical spinal infections (pSSIs) are a serious complication of spinal surgeries, with Staphylococcus spp. being one of the most prominent bacteria identified. Optimal antimicrobial therapy for staphylococcal spinal infections without spinal implants is not well documented.

Methods

This single center retrospective 7-year observational study described and compared the outcome (treatment failure or mortality at 1 year) of 20 patients with staphylococcal-implant-free pSSI treated with single or combination antibiotics.

Results

Median duration of treatment was 40 days (IQR 38–42), with 6 days (IQR 5–7) on intravenous antibiotics and 34 days (IQR 30–36) on oral therapy. Four patients (20%) underwent new surgical debridement, all due to surgical failure, and 1 patient died within the first year without statistical differences between both group of treatment.

Conclusion

This study raises the possibility of single antibiotic therapy for patients with implant-free post-surgical spinal infections due to Staphylococcus spp.

staphylococcus

spinal

surgical site infections (SSIs)

implant-free

single antibiotic

combination antibiotic

Post-surgical spinal infections (pSSI) are a common complication of spinal surgery (1), associated with high morbidity rates due to functional sequelae (2) and mostly caused by Staphylococcus aureus (1, 3). The optimal antibiotic therapy for staphylococcal spinal infections is not well documented, especially in the absence of spinal implantation. The relevance of a systematic dual antibiotic therapy and in particular the use of rifampin in combination, although recommended by some, is discussed by others (4–7). We aimed to describe and compare the clinical outcome of staphylococcal implant-free pSSIs in patients treated with a single or a combination antibiotic therapy.

We conducted a monocentric, retrospective observational study at Georges Pompidou European hospital. All adult (≥ 18 years old) patients having a staphylococcal pSSI between 1st of January 2014 and 1st of May 2021 were included. Staphylococcal pSSIs were defined by association of clinical and/or biological signs as previously described (3) associated with microbiological positivity of surgical site cultures (≥ 1/5 for Staphylococcus aureus ; ≥ 3/5 for coagulase-negative staphylococci). Exclusion criteria were retention of spinal implants after revision surgery, infections documented with other bacterial genus than Staphylococcus spp., death during the first 14 days of treatment or less than 12-month follow-up.

All patients were treated according to standard procedures and managed by the local antibiotic stewardship team. Empiric antibiotic treatment included vancomycin with cefepim and gentamicin for maximum 2 days as previously described (3), followed by targeted antibiotic therapy according to microbiological identification. Revision surgery was performed as previously described (3). Any antibiotic change was considered significant if duration lasted more than 14 days.

New surgical interventions were classified as : i) Surgical failure in case of early revision prior to the end of antibiotic therapy with no other micro-organisms identified in culture ii) Superinfection in case of new surgical procedure with identification of microorganisms different than the one previously identified, iii) Persistent infection in case of early revision in the course of antibiotic intake with renewed identification of the same microorganism as the one previously identified iv) Relapse in case of revision after the end of initial antibiotic treatment with identification of the same micro-organism as the one initially identified.

Microbiological failure was defined as any surgical revision due to iii) or iv), the occurrence of a new infection with the same microorganism or a suspected infection relapse.

The primary endpoint was a composite criterion including the rate of microbiological failure and all-cause mortality at 1 year after the diagnosis of staphylococcal pSSI.

All statistical analysis were performed with R 0.99.441 software. The local ethics committee approved the study (CER APHP number #00011928, RGPD registration number 20220216145039). Detailed information letter about the study was sent to all participants.

Twenty patients with Staphylococcus pSSI were included with no difference in baseline characteristics between the single or the combination therapy group (Table 1). The initial surgery was mostly related to degenerative causes for 19 (95%) patients. All patients presented local signs of pSSI and 6 (30%) had fever (T°> 38°C) with no signs of severity. Staphylococcus aureus was isolated in 80% of surgical samples, all methicillin-susceptible (Table 1).

Table 1

**Patients characteristics, clinical presentation and microbiology**
	Overall (N = 20)	Single therapy (N = 11)	Combination therapy (N = 9)	P value
Patients characteristics
Men (n, %)	10 (50.0%)	6 (54.5%)	4 (44.4%)	1.00
Age (year), (median [IQR])	60.0 [47.5;69.2]	60.0 [52.0;74.0]	57.0 [46.0;67.0]	0.27
BMI (kg/m²), (median [IQR])	26.0 [23.2;27.7]	26.1 [23.3;29.3]	25.3 [23.0;26.4]	0.69
eGFR (ml/min/1.73m²) (median [IQR])	94.5 [78.5;111]	95.0 [71.5;114]	91.0 [84.0;109]	0.76
Charlson score (with age) (median [IQR])	2.00 [0.75;4.25]	4.00 [0.50;6.50]	2.00 [1.00;2.00]	0.17
ASA score (median [IQR])	2.00 [1.00;3.00]	2.00 [1.50;3.00]	1.00 [1.00;2.00]	0.20
Primary surgery characteristics
Number of previous spinal surgery (median [IQR])	1.00 [1.00;1.00]	1.00 [1.00;1.00]	1.00 [1.00;1.00]	0.67
Surgical indication
Degenerative spine disease	19 (95.0%)	10 (90.9%)	9 (100%)	1.00
Vertebral metastasis	1 (5.00%)	1 (9.09%)	0 (0.00%)
Spinal implants	2 (10.0%)	2 (18.2%)	0 (0.00%)	0.48
Extent of surgery (number of vertebrae involved)	3.00 [2.00;4.00]	4.00 [2.50;4.50]	2.00 [2.00;3.00]	0.05
Post-surgical spinal infection
Delay between first surgery and new intervention (days) (median [IQR])	22.5 [17.8;29.8]	23.0 [19.5;32.0]	22.0 [17.0;24.0]	0.45
Local signs of infection (n, %)	20 (100%)	11 (100%)	9 (100%)	1.00
Fever (n, %)	6 (30.0%)	4 (36.4%)	2 (22.2%)	0.64
Site of involvement (n, %)
Cervical spine	4 (20%)	3 (27,3%)	1 (11,1%)	0.22
Thoracic spine	1 (5%)	1 (9,09%)	0 (0%)
Lumbar spine	15 (75%)	7 (36,6%)	7 (77,8%)
Sacral spine	3 (15%)	0 (0%)	3 (33,3%)
Number of vertebrae involved (median [IQR])	2.50 [2.00;4.00]	4.00 [2.00;4.00]	2.00 [2.00;3.00]	0.13
Positive blood culture, (n, %)	0	0	0
Positive surgical cultures if surgery performed (n, %)	20 (100%)	11 (100%)	9 (100%)	1.00
Implant removal (n, %)	2 (10.0%)	2 (18.2%)	0 (0.00%)
Staphylococcus aureus (n, %)	16 (80.0%)	9 (81.8%)	7 (77.8%)	1.00
Wild type (n, %)	4 (25.0%)	3 (33.0%)	1 (14.0%)
methicillin susceptible (n, %)	16 (100%)	9 (100%)	7 (100%)
fluoroquinolone resistant (n, %)	0	0	0
rifampicin resistant. (n, %)	0	0	0
Coagulase negative staphylococci (%)	4 (20.0%)	2 (18.2%)	2 (22.2%)	1.00
methicillin susceptible (n, %)	2 (50%)	1 (50%)	1 (50%)
methicillin resistant (n, %)	2 (50%)	1 (50%)	1 (50%)
fluoroquinolone resistant (n, %)	2 (50%)	1 (50%)	1 (50%)
rifampicin resistant (n, %)	0	0	0
Abbreviations: eGFR, estimated Glomerular filtration rate; BMI, body mass index ; IQR, interquartile range

The most common intravenous antibiotic used was cefazolin (12 patients, 60%), followed by amoxicillin (3 patients, 15%). A switch to oral therapy was possible for all patients. Levofloxacin with clindamycin was the main oral combination prescribed (4 patients, 44%), followed by levofloxacin with rifampin (3 patients, 33%).

Eleven patients (55%) were treated with single antibiotic therapy, with clindamycin being the main antibiotic used (5 patients, 46%) (Table 2).

Table 2

Treatment and outcomes
	Overall (N = 20)	Single therapy (N = 11)	Combination therapy (N = 9)	P value
Duration of intravenous antibiotics, days (median [IQR])	6.00 [4.75;7.25]	7.00 [4.50;12.5]	5.00 [5.00;6.00]	0.25
Duration of oral antibiotics, days (median [IQR])	34.0 [29.5;36.0]	33.0 [27.0;35.5]	36.0 [33.0;37.0]	0.12
Total duration on antibiotics, days (median [IQR])	40.0 [38.0;41.5]	40.0 [38.0;41.0]	41.0 [38.0;43.0]	0.76
Intravenous antibiotics used
Cefazoline (n, %)	12 (60.0%)	6 (54.5%)	6 (66.7%)	0.24
Amoxicillin (n, %)	3 (15.0%)	3 (27.3%)	0 (0.00%)
Cloxacillin (n, %)	2 (10.0%)	0 (0.00%)	2 (22.2%)
Vancomycin (n, %)	2 (10%)	1 (9%)	1 (11.1%)
Daptomycin (n, %)	1 (5.00%)	1 (11.1%)	0 (0%)
Switch to oral antibiotics (number, %)	20 (100%)	11 (100%)	9 (100%)	1.00
Oral antibiotics used
Levofloxacin (n, %)	11 (55.0%)	3 (27.3%)	8 (88.9%)	0.08
Clindamycin (n, %)	9 (45.0%)	5 (45,5%)	4 (44.4%)
Amoxicillin (n, %)	4 (20.0%)	2 (18.2%)	2 (22.2%)
Rifampin (n, %)	3 (15.0%)	0 (0%)	3 (33.3%)
Doxycycline (n, %)	1 (5.00%)	0 (0.00%)	1 (11.1%)
Linezolid (n, %)	1 (5.00%)	1 (9.09%)	0 (0.00%)
Patients undergoing new surgical debridement (n, %)	4 (20.0%)	3 (27.3%)	1 (11.1%)	0.59
Patients with microbiological failure (n, %)	0	0	0
Deaths from any cause at 1 year (n, %)	1 (5%)	0	1 (11,1%)
Primary endpoint ((n, %)	1 (5.00%)	0 (0.00%)	1 (11.1%)	0.45
Deaths from any cause during follow-up (n, %)	2 (10.0%)	0 (0.00%)	2 (22.2%)	0.19
Duration of follow-up, days (median [IQR])	1024 [580;1512]	862 [573;1157]	1493 [699;1715]	0.18

Only one patient reached the primary endpoint (death at 135 days) due to end-stage heart failure without any link to spinal infection (Table 2). Four patients (20%) underwent new surgical debridement (3/4 in the single antibiotic group) because of healing defect, with no micro-organisms found on surgical cultures. We didn’t report any microbiological failure during follow-up on both treatment groups. We reported 2 deaths (10% mortality rate) during all follow-up, due to complications of underlying diseases. There was no outcome difference between single antibiotic therapy and combination therapy (Table 2).

We here described the results of a retrospective cohort of staphylococcal implant-free pSSI treated with either single or combination antibiotics. Patients had few underlying diseases and good outcome with 95% of success at 1 year. We described four revision surgeries, none due to persistent infection or relapse. Despite a long median length of follow-up of almost 3 years, only 1 death occurred during the first year, unrelated to surgery or antibiotic treatment.

Overall, there was a low number of failures reported in contrast to previous studies with failure rates ranging from 0.5–3.6% (2, 8), explained by several factors: i) we may have missed long-term relapses, ii) patients were not at high risk of relapse due to low number of underlying diseases and absence of methicillin-resistant S. aureus (3, 9).

To our knowledge, this is the first study focusing on antibiotic treatment modalities of implant-free post-surgical spinal infections with no outcome difference identified between both groups. In several studies about pSSI combining infections with and without implant removal, combination treatment with biofilm-active antibiotics was associated with lower treatment failure (9, 10). However, in the study by Cho et al., this effect was not significant in case of methicillin-susceptible S. aureus infection or implant removal (9). In our study, clindamycin and levofloxacin were the main single antibiotic prescribed, allowing conclusion of efficacy to be drawn on these two antibiotics only. One quarter of S. aureus isolates were susceptible to penicillin G and interestingly 3 out of them were treated with amoxicillin with satisfactory outcome.

Although we presented a small sample size, it is however to date the largest study of implant-free staphylococcal pSSI treated with a single antibiotic therapy. We suggest that a single antibiotic treatment with clindamycin or levofloxacin could be as efficient as a combination therapy in implant-free post-surgical staphylococcal spinal infection in patients with few underlying diseases. A randomized control trial should be conducted to confirm these results.

PSSI

Post-surgical spinal infections

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The ethics committee “Comité d’éthique de recherche APHP Paris Ouest” approved the study (CER APHP number #00011928, RGPD registration number 20220216145039). Detailed information letter about the study was sent to all participants. Informed consent was obtained from all subjects. All methods were carried out in accordance with relevant guidelines and regulations.

CONSENT FOR PUBLICATION

Not applicable.

AVAILABILITY OF DATA AND MATERIAL

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

COMPETING INTEREST

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

FUNDING

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

AUTHORS’ CONTRIBUTIONS

A.L drafted the manuscript. M.D and A.L designed the figures. M.D performed statistical analysis. M.P.F.G, M.K, N.K.C, A.J, J.L.M, D.L and M.D revised the manuscript. N.K.C, M.D, M.P.G and D.L participated in the creation of the database. All authors read, revised and approved the final manuscript.

ACKNOWLEDGMENTS

Not applicable.

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No competing interests reported.

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You are reading this latest preprint version

Efficacy of single antibiotic therapy versus antibiotic combination in implant-free staphylococcal spinal infections: a retrospective observational study

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Abstract

Background

Methods

Results

Conclusion

1. INTRODUCTION

2. MATERIAL AND METHODS

3. RESULTS

4. DISCUSSION

Abbreviations

Declarations

References

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Journal Publication

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