Comparative study of reliability of inflammatory markers over 18-FDG−PET CT scan in monitoring skull base osteomyelitis

Faizal, Bini; Surendran, Bhavya; Kumar, Madhumita

doi:10.1016/j.bjorl.2020.09.012

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Brazilian Journal of Otorhinolaryngology

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Original article • Braz. j. otorhinolaryngol. 88 (05) • Sep-Oct 2022 • https://doi.org/10.1016/j.bjorl.2020.09.012 copy

Comparative study of reliability of inflammatory markers over 18-FDG−PET CT scan in monitoring skull base osteomyelitis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction

The end point of treatment in skull base osteomyelitis is a matter of debate. A treatment based on symptoms alone is fraught with recurrence. There is a need to restrict imaging though more informative. The inflammatory markers like C-reactive protein and erythrocyte sedimentation rate used commonly need a detailed evaluation to optimize its utility.

Objectives

To compare the diagnostic accuracy of inflammatory markers with a hybrid PET scan in monitoring skull base osteomyelitis. The secondary objective was to obtain a cut-off value of these markers to decide upon antibiotic termination.

Methods

A prospective cohort study was conducted in a tertiary care center with fifty-one patients with skull base osteomyelitis meeting eligibility criteria. Patients diagnosed with skull base osteomyelitis were serially monitored with weekly markers and PET scan after the initiation of treatment. A hybrid scan was taken at 6-8 weeks of treatment and repeated if required. The follow-up period varied from 6 weeks to 15 months. The outcome measures studied were the values of markers and the metabolic activity of PET scan when the patient became asymptomatic and when disease-free.

Results

C-reactive protein and erythrocyte sedimentation rate had a statistically significant correlation to disease activity in PET tomography scan as a prognostic marker. Both showed good clinical correlation. A cut off value of ≤ 3.6 mg/L for C-reactive protein and ≤ 35 mm/hour for erythrocyte sedimentation rate were taken as normalized values.

Conclusion

A consistent normalized value of C-reactive protein and erythrocyte sedimentation rate for 8-12 weeks in an asymptomatic patient may be an indicator of disease control, though not cure. So, relying solely on markers alone for antibiotic termination may cause relapse. It may be used cautiously in a peripheral setting without access to more specific hybrid scans. In a tertiary care, follow-up scans may be done based on the titres, thereby limiting the radiation exposure.

Keywords
C-Reactive protein; Blood sedimentation; Positron-emission tomography; Skull base; Osteomyelitis

	n = 51	Percentage (%)
Gender
Female	12	23.5
Male	39	76.5
Diabetes mellitus	48	94.1
Microbial flora
Pseudomonas aeruginosa	11	21.6
Aspergillus species	6	11.8
Candida species	5	9.8
Staphylococcus aureus	2	3.9
No cultures/polymicrobial growth	16	31.4
Debridement	28	54.9

S nº	Age (yrs)	Sex	Diagnosis	CRP						ESR						Initial PET activity	PET CT final	Culture	Medical management	Debridement/ Blopsy	Asymptomatic status/ Treatment status
S nº	Age (yrs)	Sex	Diagnosis	Week1	Week2	Week3	Week4	Week5	Week6	Week1	Week2	Week3	Week4	Week5	Week6	Initial PET activity	PET CT final	Culture	Medical management	Debridement/ Blopsy	Asymptomatic status/ Treatment status
1	67	M	MOE	3.5	18	6.4	29	27	28	29	28	51	59	99	102	Not done	No	No growth	Itraconazole/ piptaz/ciplox	Yes	3 months
2	76	M	Central SBO	0.5	32	71	26	7	2	7	25	81	74	72	44	Yes	No	Aspergillus flavus	Inj fortum/ voricoazole/ ciplox	Yes	4 months
3	53	M	Central SBO	11	20	13	9	4	4	55	55	56	40	36	10	Yes	Yes	Klebsiella	Linezolid and vancomycin, magnex voriconazole, meropenem, minocycline	Yes	3 months
4	62	F	Central SBO	23	30	38	20	15	9	91	101	83	56	34	30	Yes	No	No culture	Ceftazidime, amikacin and metrogyl, IV magnex and oral linezolid and voriconazole, piptax and ciplox	Yes	6 weeks
5	65	M	Central SBO	24	117	68	23	21	14	107	108	113	108	97	50	Yes	No	No growth	Piperacillin, voriconazole	Yes	Lost for follow up
6	61	M	Central SBO	91	74	54	63	47	34	56	74	61	34	67	54	Yes	No	Aspergillus flavus	Voriconazole	Yes	5 months
7	64	F	Central SBO	13	10	9	4	3	2	19	52	54	43	40	38	Yes	Yes	Chryosporim, Pseudomonas acruginosa	Ceftazidime, voriconazole, ciprofloxacin, fluconazole	Yes	2 months
8	55	M	Central SBO	24	110	68	23	21	14	98	108	103	108	97	50	Yes	No	No culture	Ceftazidime	No	2 months
9	70	M	Central SBO	11	20	13	9	4	4	55	55	56	40	36	30	Yes	Yes	No culture	Piperacillin	No	Passed away
10	73	M	Central SBO	25	21	16	10	5	2	95	104	87	60	54	43	Yes	No	Candida para psilosis	Voriconazole, piperacillin, meropenem	Yes	6 weeks
11	45	M	Central SBO	24	21	15	8	3	1	67	80	57	65	45	14	Yes	No	Staph aureus	Voriconazole, piperacillin, clindamycin, cloxacillin, linezolid, ciprofloxacin	Yes	On antibiotics for 1 yr and a month, patient had symptomatic relief after 2 months
12	78	M	MOE	40	32	25	20	15	5	90	74	70	35	44	52	Yes	No	Pseudomonas, Candida Albinas	Ciprofloxacin and cefaperazone	No	2 months
13	60	M	Central SBO	0.7	3.6	4	4.2	3	3.3	70	96	103	97	88	58	Yes	No	Enterococcus fecalis	Ceftazidime, ciprofloxacin, piperacillin, linezolid, fluconazole	Yes	Lost for follow up
14	66	F	MOE	40	43	38	21	22	4	70	34	42	68	52	34	Yes	No	No growth	Ceftazidime, ciprofloxacin, voriconazole	No	Lost for follow up after 6 months IV and voriconazole
15	66	M	MOE	1.5	5.1	4	2.3	1.9	0,7	40	73	57	52	40	46	Yes	No	Gram negative bacteria	Piperacillin voriconazole, itraconazole	No	2 months
16	78	M	MOE	20	17	10	9	9.2	1	60	61	58	44	30	29	Yes	No	No growth	Ceftazidime	Yes	2 months
17	63	M	Central SBO	30	120	210	344	400	412	70	77	92	100	90	102	Yes	Yes	No growth	Piperacillin voriconazole, clindamycin	Yes	Antibiotics for 1 month, expired due to septic shock
18	77	M	MOE	6.5	16	22	30	32	23	54	44	40	36	28	18	Yes	Yes	Citrobacter kooseri, Klebsiella pneumoniae, enterococcus faecalis	Ceftazidime, ciprofloxacin	Yes	2 months
19	65	M	MOE	36	106	88	42	56	2	86	74	66	42	30	36	Yes	Yes	Pseudomonas aeruginosa	Ciprofloxacin, piperacillin	Yes	2 months
20	68	M	Central SBO	10	22	8.04	4	1.3	11	96	42	36	53	50	52	Yes	Yes	Candida hemulonii	Meropenem, voriconazole	Yes	6 months
21	72	M	Central SBO	47	79	13	31	26	23	96	107	97	90	88	80	Yes	Yes	Kodamea ohmeri	Cefaperazone, voriconazole, amphotericin	No	6 months
22	73	M	MOE	10	7.2	9.6	6	8	9.8	83	72	94	79		87	Yes	Yes	Pseudomonas aeruginosa	Cefaperazone, ciprofloxacin, piperacillin, voriconazole	Yes	4 weeks of piptaz and 4 months of voriconazole
23	59	M	MOE	23	20	16	10	4	2	74	55	42	33	20	28	Yes	No	No culture	Piperacillin, ciprofloxacin	No	6 weeks
25	62	M	MOE	11	6.1	5.5	10	17	19	49	45	36	51	59	64	Yes	Yes	Pseudomonas, Klebsiella, Streptococcus	Piperacillin, voriconazole	Yes	8 months of voriconazole and 3 months of piptaz
26	74	F	Central SBO	16	10	8	2	1.4	0.8	46	43	36	29	20	16	Yes	No	Aspergillus flavus	Voriconazole, cefaperazone, ciprofloxacin	No	2 months
27	72	M	Central SBO	20	16	12	8	4	2	51	50	40	44	35	38	Yes	No	No growth	Ceftazidime, ciprofloxacin, piperacillin, linezolid, fluconazole	No	2 months
28	64	F	MOE	31	15	34	98	108	9	81	46	42	44	34	20	Yes	No	Pseudomonas aeruginosa	Ceftazidime	No	6 weeks
29	61	M	MOE	7	16	18	15	93	1.3	50	61	76	85	53	25	Yes	No	Pseudomonas aeruginosa	Piperacillin, cefoperazone, voriconazole	Yes	3 months
30	71	M	Central SBO	43	13	6.5	6.07	5	3.2	69	81	68	40	42	38	Yes	No	No growth	Cefaperazone, ciprofloxacin	Yes	2 months
31	68	M	Central SBO	1.4	17	16	13	14.5	14	50	54	90	92	66	60	Yes	Yes	No culture	Voriconazole, linezolid	No	7 weeks of voriconazole
32	60	M	MOE	71	57	12.57	6.5	5.19	1.62	97	94	83	47	25	14	Yes	No	No growth	Piperacillin, meropenem	Yes	3 months
33	70	M	MOE	11.58	11.94	27	24	10	2.28	61	56	81	32	35	30	Yes	No	Candida non albicans (SG), Pseudomonas aeruginosa (SG)	Voriconazole, amphotericin B, doxycycline	Yes	2 months
34	80	F	MOE	9.3	19	5.79	10.85	9.9	8	90	69	88	17	62	60	Yes	Yes	No growth	Vancomycin, meropenem, voriconazole	No	10 weeks
35	63	F	Central SBO	8.59	11.19	10	9	6	5.6	97	30	32	40	20	18	Yes	No	No growth	Ceftazidime	No	6 weeks
36	70	F	Central SBO	17.68	24.46	67.31	50	46	30	37	57	60	48	32	50	Yes	Yes	Staphaureus (MG), Candida albicans	Ceftazidime, ciprofloxacin	No	Lost for follow up after 4 weeks
37	56	F	Central SBO	10	18.92	16	14	8.4	563	60	63	71	74	65	60	Yes	Yes	No culture	Voriconazole	No	4 months
38	54	M	MOE	4.76	4.7	11.5	11	16.8	4,3	37	47	57	47	30	36	Yes	Yes	Candida no albicans (MG)	Meropenem, voriconazole	Yes	6 months
39	62	M	Central SBO	10	7	5	3	11	9	46	47	44	38	42	40	Yes	Yes	Pseudomonas aeruginosa (MG)	Ceftazidime	No	2 months
40	75	M	MOE	3	2	54	15	2	0.93	23	23	30	27	10	5	Yes	No	Candida albicans	Ceftazidime	No	6 weeks
41	75	M	MOE	20	22	35	40	30	20	44	50	38	30	67	100	Yes	Yes	Aspergillus flavus, enterobacter sp.	Ciprofloxacin, cefaperazone	Yes	6 months
42	73	M	MOE	11	31	20	14	9.14	1.66	103	100	100	115	80	70	Yes	Yes	Invase aspergillosis	Ciprofloxacin, cefaperazone	Yes	2 months
43	71	M	MOE	8.38	17.26	22.4	20	15	13.2	30	80	54	40	60	76	Yes	Yes	No growth	Ciprofloxacin, ceftazidime	Yes	< 8 months
44	75	M	Central SBO	66	54	6.8	2.1	4	5	12	15	8	14	7	6	Yes	No	Pseudomonas aeruginosa (moderate growth), Staphylococcus aureus	Ciprofloxacin, cefaperazone	No	3 months
45	65	F	MOE	152	112	95	88	70	73	74	74	80	64	123	80	Yes	Yes	Aspergillus fumigatus	Cefaperazone, ciprofloxacin, voriconazole	No	Lost for follow up after 6 weeks
46	71	M	MOE	47	70	13	31	26	2	90	100	97	90	80	19	Yes	Yes	Staph aureus, ryosporium sp.	Voriconazole, terbinafine	Yes	6 months
47	70	F	MOE	4.76	4.7	11.5	12	16.8	4.3	60	50	52	38	32	24	Yes	No	Pseudomonas aeruginosa (scanty growth)	Ciprofloxacin, ceftazidime,	No	3 months
48	57	M	MOE	24.9	1,3	22.4	80.9	52	34	38	30	24	18	20	67	Yes	Yes	Pseudomonas aeruginosa (heavy growth)	Ceftazidime, piperacillin	Yes	Lost for follow up after 4 months
48	62	F	Central SBO	12	6.1	5.5	10	2.32	1.38	30	44	50	19	52	27	Yes	No	Pseudomonas aeruginosa, cryosporium	Ceftazidime, ciprofloxacin	Yes	2 months
50	69	M	Central SBO	31	13	34	98	108	10	81	42	42	44	34	20	Yes	No	Aspergillus flavus	Ciprofloxacin, cefaperazone, itraconazole	No	3 months
51	88	M	Central SBO	22.56					8.4	70					60		No	Pseudomonas aeruginosa	Ceftazidime, ciprofloxacine	No	3 months

Inflammatory markers		FDG-PET CT metabolic activity (n = 51)		p-value
Inflammatory markers		Absent, n (%)	Present, n (%)	p-value
ESR (mm/hr)	≤ 35	16 (57.1%)	6 (26.1%)	0.026^a a Statistically significant correlation between ESR and metabolic activity in FDG PET at the end of two months.
	> 35	12 (42.9%)	17 (73.9%)
	≤ 3.65	17 (60.7%)	4 (17.4%)	0.002^b b Statistically significant correlation between CRP and disease activity in FDG PET at the end of two months.
CRP	>3.65	11 (39.3%)	19 (82.6%)

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[1] * Corresponding author. binifaizal@gmail.com (B. Faizal).