Treatment of late bacterial infections resulting from soft-tissue filler injections

Figures & data

Table 1 Description of study participants

Age (years)	Site of HA injection	HA volume (mL)	Time between HA injection and biofilm formation (months)	Site affected by biofilm	Diameter of lesion (cm)
48	Nasolabial folds, corners of mouth	1	6	Right corner of mouth	≤2
49	Tear troughs, nasolabial folds, lips	3	4	All areas treated	≤2
59	Tear troughs, cheeks, chin	6	2	Right cheek	≤2
31	Tear troughs	1	10	Right tear trough	Orbital cavity
37	Nasolabial folds, corners of mouth, lips	2	4	Right nasolabial fold	≤2
47	Nasolabial folds, corners of mouth	1	1	Left nasolabial fold	≤2
53	Tear troughs, nasolabial folds	2	2	Right tear trough	Orbital cavity
38	Cheeks	2	2	Right cheek	≤2
68	Cheeks	2	1	All areas treated	≤2
41	Tear troughs, nasolabial folds, eyebrow ridge	2	3	All areas treated	≤2
58	Cheeks	2	5	All areas treated	≤3
56	Nasolabial folds	1	2	All areas treated	≤2
39	Tear troughs, nasolabial folds	2	2	Left tear trough	Orbital cavity
62	Nasolabial folds, corners of mouth	2	3	All areas treated	≤2
56	Cheeks	2	18	Right cheek	≤2
62	Nasolabial folds	2	2	All areas treated	≤2
30	Tear troughs, both cheeks, lips	4	4	Right tear trough	Orbital cavity
45	Lower face, marionette lines	1	1	Corners of mouth	≤1
35	Wrinkles between eyebrows	1	1	Near right eyebrow, close to nose	≤1
44	Forehead	1	1	Forehead above left eyebrow	≤1
36	Tear troughs, edges of mandible, forehead, temples, lips, nasolabial folds	3	1	Both tear troughs	Both orbital cavities
47	Cheeks, chin	3	4	Chin	≤2

Abbreviation: HA, hyaluronic acid.

Table 2 Variation in hyaluronidase dose with size of inflammatory facial swelling or nodule

Diameter of swelling or nodule (cm)a	≤0.5	≤1	≤1.5	≤2	≤2.5	≤3	In orbital cavity
Each hyaluronidase dose (units)b	45	75	105	135	165	195	6–24

Notes:

a Assessed based on the diameter measured between the opposite rims that were furthest apart.

b There are routinely six units per injection.

Table 3 Description of the groups

	Age (years)			HA volume (mL)			Time between HA injection and biofilm formation (months)			Treatment duration (days)
	Mean	Median	SD	Mean	Median	SD	Mean	Median	SD	Mean	Median	SD
Patients cured using M&N scheme (n=17)	49.1	49.0	11.5	2.2	2.0	1.2	4.2	3.0	4.2	16.9	14.0	3.6
Subgroup 1	44.8	48.0	11.0	2.6	2.0	2.1	5.0	4.0	3.0	15.4	14.0	3.1
Subgroup 2	50.8	54.5	11.7	2.0	2.0	0.7	3.7	2.0	4.6	17.5	17.5	3.7
Subgroup 3	41.4	44.0	5.5	1.8	1.0	1.1	1.6	1.0	1.3	32.0	14.0	33.0

Abbreviations: HA, hyaluronic acid; M&N, Marusza and Netsvyetayeva.

Table 4 Description of participants treated with M&N scheme as first therapeutic option

Age (years)	Site of HA injection	HA volume (mL)	Nodulediameter (cm)	Time between HA injection and biofilm formation (months)	Site affected by biofilm	Relapse	HA injection after recovery	No biofilm relapse 2 years after recovery
48	Nasolabial folds, corners of mouth	1	≤2	6	Right corner of mouth	No	Yes	Yes
49	Tear troughs, nasolabial folds, lips	3	≤2	4	All areas treated	No	Yes	Yes
59	Tear troughs, cheeks, chin	6	≤2	2	Right cheek	No	Yes	Yes
31	Tear troughs	1	Orbital cavity	10	Right tear trough	No	Yes	Yes
37	Nasolabial folds, corners of mouth, lips	2	≤2	4	Right nasolabial fold	No	Yes	Yes

Notes: Comprehensive treatment in accordance with the M&N scheme: puncture of the lesion and drainage of pus and fermented HA. Orally administered combination antibiotic and probiotic therapy: 2×400 mg moxifloxacin + 2×500 mg clarithromycin + probiotic formulation consisting of 1.6 billion CFU lyophilized strains of Lactobacillus acidophilus, L. delbrueckii subsp. bulgaricus, and Bifidobacterium lactis, three capsules a day. Duration of antibiotic therapy: 14–21 days or until the complete resolution of swelling and nodules (whichever is longer). Duration of probiotic treatment: during the antibiotic therapy and 1 month after its termination. Duration of locally administered hyaluronidase treatment: 14–21 days or until the complete resolution of swelling and nodules (whichever was longer). Hyaluronidase dosage: according to Table 2.

Abbreviations: M&N, Marusza and Netsvyetayeva; HA, hyaluronic acid; CFU, colony-forming unit.

Table 5 Description of participants successfully treated in accordance with the M&N scheme after unsuccessful treatment with other schemes

Age (years)	Site of HA injection	HA volume (mL)	Nodulediameter (cm)	Time between HA injectionand biofilm formation (months)	Site affected by biofilm	First therapeutic option, antibiotics	First therapeutic option, hyaluronidase	Relapses, n	No symptom resolution	Relapse, site affected by biofilm	Relapse, nodule diameter (cm)	Relapse, cause	Relapse/no symptom resolution, comprehensive treatment in accordance with the M&N scheme	Relapse/no symptom resolution, duration of treatment in accordance with the M&N scheme (days)	Relapse/no symptom resolution, treatment with hyaluronidase	HA injection after recovery	No biofilm relapse 2 years after recovery
47	Nasolabial folds, corners of the mouth	1	≤2	1	Left nasolabial fold	Ciprofloxacin 2×500 mg, clarithromycin 500 mg, Trilac 3×1 caps per os; duration in accordance with M&N scheme	Yes, in accordance with M&N scheme	1	–	Same area	≤2	Administering HA	Yes	14	Yes	No	Yes
53	Tear troughs, nasolabial folds	2	Orbital cavity	2	Right tear trough	Ciprofloxacin 2×500 mg, clarithromycin 500 mg, Trilac 3×1 caps per os; duration in accordance with M&N scheme	Yes, in accordance with M&N scheme	1	–	Same area	Orbital cavity	Administering HA	Yes	14	Yes	Yes	Yes
38	Cheeks	2	≤2	2	Right cheek	Cefalexin 2×500 mg for 10 days per os, then doxycycline 100 mg for 10 days per os	No (patient refused)	–	Yes: infected HA not completely removed (nodule 5 mm in diameter remained)	–	–	–	Yes	21	No	Yes	Yes
68	Cheeks	2	≤2	1	All areas treated	Ciprofloxacin 2×500 mg, clarithromycin 500 mg, Trilac 3×1 caps per os, duration in accordance with M&N scheme	Yes, in accordance with M&N scheme	1	–	New area: over the right eyebrow and the right cheek	<1 cm	Administering HA in the eyebrow area, new site	Yes	21	Yes	Yes	Yes
41	Tear troughs, nasolabial folds, eyebrow ridge	2	≤2	3	All areas treated	Ciprofloxacin 2×500 mg, clarithromycin 500 mg, Trilac 3×1 caps per os, duration in accordance with M&N scheme	Yes, in accordance with the M&N scheme	1	–	Same area	≤2	Administering HA	Yes	21	Yes	Yes	Yes
58	Cheeks	2	≤3	5	All areas treated	Ciprofloxacin 2×500 mg, clarithromycin 500 mg, Trilac 3×1 caps per os for 14 days. Then, during hospitalization: metronidazole 3×500 mg, amoxicillin– clavulanate 3×2.1 g IV, hydrocortisone IV 200 mg for 7 days	No (doctor did not apply scheme)	–	Yes	–	–	–	Yes	21	Yes	Yes	Yes
56	Nasolabial folds	1	≤2	2	All areas treated	Ciprofloxacin 2×500 mg, Clarithromycin 500 mg, Trilac 3×1 caps per os, duration in accordance with M&N scheme	Yes, in accordance with M&N scheme	4	–	Same area	≤2	Administering HA, each time	Yes, as well as tooth extraction and treatment of both infected mandibular sinuses	21	Yes	No	Yes
39	Tear troughs, nasolabial folds	2	Orbital cavity	2	Left tear trough	Ciprofloxacin 2×500 mg, clarithromycin 500 mg, Trilac 3×1 caps per os, duration in accordance with M&N scheme	Yes, in accordance with the M&N scheme	1	–	Same area	Orbital cavity	Spontaneous	Yes	14	Yes	Yes	Yes
62	Nasolabial folds, corners of the mouth	2	≤2	3	All areas treated	Cefalexin 4×500 mg, clindamycin 3×300 mg per os for 14 days, then incision and draining and gentamicin 3×80 mg IV for 5 days	No (doctor did not apply the scheme)	–	Yes	–	–	–	Yes	14	Yes	No	Yes
56	Cheeks	2	≤2	18	Right cheek	Clarithromycin 500 mg, amoxicillin– clavulanate 3×1 g, Trilac 3×1 caps per os	Yes, in accordance with M&N scheme	1	–	Same area	≤2	Spontaneous	Yes	14	Yes	Yes	Yes
62	Nasolabial folds	2	≤2	2	All areas treated	Clindamycin 4×300 mg per os for 9 days, then metronidazole 2×500 mg per os, abscess incision from the side of the mouth, and drainage of the lesion thrice	No (doctor did not apply scheme)	–	Yes	–	–	–	Yes	21	Yes	No	Yes
30	Tear troughs, both cheeks, lips	4	Orbital cavity	4	Right tear trough	Clarithromycin 500 mg, Trilac 3×1 caps per os, duration in accordance with M&N scheme	Yes, in accordance with M&N scheme	1	–	New area: tear trough under the left eye	Orbital cavity	Spontaneous	Yes	14	Yes	Yes	Yes

Notes: Comprehensive treatment in accordance with the M&N scheme: puncture of the lesion and drainage of pus and fermented HA. Orally administered combination antibiotic and probiotic therapy: 2×400 mg moxifloxacin + 2×500 mg clarithromycin + probiotic formulation consisting of 1.6 billion CFU lyophilized strains of Lactobacillus acidophilus, L. delbrueckii subsp. bulgaricus, and Bifidobacterium lactis, three capsules a day. Duration of antibiotic therapy: 14–21 days or until complete resolution of swelling and nodules (whichever is longer). Duration of probiotic treatment: during antibiotic therapy and 1 month after its termination. Duration of locally administered hyaluronidase treatment: 14–21 days or until complete resolution of swelling and nodules (whichever was longer). Hyaluronidase dosage: according to Table 2.

Abbreviation: M&N, Marusza and Netsvyetayeva; HA, hyaluronic acid; IV, intravenous.

Table 6 Participants (subgroup 3) successfully treated by application of schemes other than M&N, description of initial treatment

Ageyears	Site of HA injection	HA Volume (mL)	Nodule diameter (cm)	Time between HA injection and biofilm formation (months)	Site affected by biofilm	First therapeutic option, antibiotics	First therapeutic option, hyaluronidase	Relapses, n
45	Lower face	1	≤1	1	Corners of the mouth	No	Immediate administration of 40 units of hyaluronidase	1
35	Wrinkles between eyebrows	1	≤1	1	Near right eyebrow, close to nose	No	In accordance with M&N scheme	–
44	Forehead above the left eyebrow	1	≤1	1	Forehead above the left eyebrow	Extended antibiotic therapy involving several doctors over 3 months. The patient had been treated with the following medications among others the patient did not remember: gentamicin 3×80 mg IM, ceftriaxone 2 g IV	No	–
36	Both tear trough valleys	3	Both orbital cavities	1	Both tear trough valleys	Clarithromycin 1×500 mg, Trilac 3×1 cap, duration in accordance with M&N Scheme	In accordance with M&N Scheme	–
47	Chin	3	≤2	4	Chin	Clarithromycin 1×500 mg, Trilac 3×1 cap, duration in accordance with M&N Scheme	In accordance with M&N Scheme	–

Notes: Comprehensive treatment in accordance with M&N scheme: puncture of the lesion and drainage of pus and fermented HA. Orally administered combination antibiotic and probiotic therapy: 2×400 mg moxifloxacin + 2×500 mg clarithromycin + probiotic formulation consisting of 1.6 billion CFU lyophilized strains of Lactobacillus acidophilus, L. delbrueckii subsp. bulgaricus, and Bifidobacterium lactis, three capsules a day. Duration of antibiotic therapy: 14–21 days or until complete resolution of swelling and nodules (whichever was longer). Duration of probiotic treatment: during antibiotic therapy and 1 month after its termination. Duration of locally administered hyaluronidase treatment: 14–21 days or until complete resolution of swelling and nodules (whichever was longer). Hyaluronidase dosage according to Table 2.

Abbreviations: HA, hyaluronic acid; IM, intramuscular; IV, intravenous; M&N, Marusza and Netsvyetayeva.

Table 7 Participants (subgroup 3) successfully treated by application of schemes other than M&N, description of relapses and recovery

Age years	No symptom resolution	Relapse, site affected biofilm	Relapse, nodule diameter (cm)	Relapse, cause	Relapse/no symptom resolution, comprehensive treatment in accordance with M&N Scheme	Relapse/no symptom resolution, treatment duration in accordance with M&N Scheme (days)	Relapse/no symptom resolution, treatment with hyaluronidase	HA injection after recovery	No biofilm relapse 2 years after recovery
45	–	Same area	≤2	Administering cross-linked HA gel	Hyaluronidase alone	No antibiotics applied	Hyaluronidase alone in accordance with M&N scheme, (Table 2)	Yes	Yes
35	–	–	–	–	–	–	–	No	Yes
44	Yes	–	–	–	No, lesion removed with laser, leaving scar tissue	No antibiotics applied	No Hyaluronidase applied	No	Yes
36	–	–	–	–	–	–	–	Yes	Yes
47	–	–	–	–	–	–	–	No	Yes

Notes: Comprehensive treatment in accordance with M&N scheme: puncture of the lesion and drainage of pus and fermented HA. Orally administered combination antibiotic and probiotic therapy: 2×400 mg moxifloxacin + 2×500 mg clarithromycin + probiotic formulation consisting of 1.6 billion CFU lyophilized strains of Lactobacillus acidophilus, L. delbrueckii subsp. bulgaricus, and Bifidobacterium lactis, three capsules a day. Duration of antibiotic therapy: 14–21 days or until complete resolution of swelling and nodules (whichever was longer). Duration of probiotic treatment: during antibiotic therapy and 1 month after its termination. Duration of locally administered hyaluronidase treatment: 14–21 days or until complete resolution of swelling and nodules (whichever was longer). Hyaluronidase dosage according to Table 2.

Abbreviations: HA, hyaluronic acid; M&N, Marusza and Netsvyetayeva.