Scientific Rationale and Clinical Basis for Clindamycin Use in the Treatment of Dermatologic Disease

Abstract

Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing fixed-combination topicals containing clindamycin that prevent Cutibacterium acnes growth and reduce inflammation associated with acne lesion formation. Certain clinical presentations of folliculitis, rosacea, staphylococcal infections, and hidradenitis suppurativa are also responsive to clindamycin, demonstrating its suitability and versatility as a treatment option. This review describes the use of clindamycin in dermatological practice, the mechanism of protein synthesis inhibition by clindamycin at the level of the bacterial ribosome, and clindamycin's anti-inflammatory properties with a focus on its ability to ameliorate inflammation in acne. A comparison of the dermatologic indications for similarly utilized antibiotics, like the tetracycline class antibiotics, is also presented. Finally, this review addresses both the trends and mechanisms for clindamycin and antibiotic resistance, as well as the current clinical evidence in support of the continued, targeted use of clindamycin in dermatology.

Keywords: acne vulgaris therapy; antibiotic treatments; antimicrobial resistance; folliculitis; furunculosis; inflammatory skin disease; skin and soft tissue infection; stewardship.

Figure 1

Interaction of Clindamycin with the 70S ribosome. Clindamycin (CLI, green), sarecycline (SAR2, gold) and erythromycin (ERI, beige) are shown as balls (top) or sticks (two bottom panels). Bottom panels are the surface representation of the NPET, with the clindamycin binding pocket depicted and CLI, SAR2, and ERI structures bound in their respective binding sites. P-site (P)-bound tRNA is shown in brown, A is the location of the A-site, and E denotes the E-site. The canonical tetracycline binding site is marked as CTBS, the decoding center as DC, the peptidyl transferase center as PTC, and the nascent peptide exit tunnel as NPET (blue). The 30S ribosomal subunit is in gray, 50S in khaki. Nitrogen atoms are blue, and oxygen atoms are red in CLI and SAR. Superposition of models with Protein Data Bank (PDB) IDs 8CRX, 4V7V, and 7NSO was used to create this figure [23,25,44]. All figures in this review were created using PyMOL Version 2.0 [45]. Abbreviations and labeling methods follow those presented in [23].

Figure 2

Clindamycin binding site in the 23S rRNA of the E. coli ribosome. Clindamycin (CLI, green) interacts with nucleotides of the 23S rRNA (cyan) as seen in the model of PDB ID 4V7V [25]. Hydrogen bonds are shown by yellow dashed lines, and van der Waals contacts are represented by gray dashed lines. To show the location of the aminoacyl moiety of the P-site (brown) and A-site (semitransparent blue) tRNAs in the PTC, the structure of the E. coli ribosome in PDB ID 7RQ8 [3] was superimposed. Nitrogen atoms are blue, and oxygen atoms are red in CLI.

Figure 3

Clindamycin binding site in the 23S rRNA is conserved. The structure of the clindamycin (CLI) binding site (cyan, as shown in Figure 2) in the E. coli ribosome (cyan) was superimposed with that of Thermus thermophilus (gold, PDB ID 7RQ8 [3], Staphylococcus aureus (gray, PDB ID 5NRG [46]) and Cutibacterium acnes (magenta, PDB ID 8CRX [23]). Nucleotide U2506 is positioned differently in the C. acnes ribosome structure because this structure had no antibiotic bound to the PTC. This model suggests that the binding of clindamycin to C. acnes will induce a conformational change in U2506. Nitrogen atoms are blue, and oxygen atoms are red in CLI.

Figure 4

Interaction of clindamycin with the LinB enzyme. Ribbon diagram of LinB depicted on the left. The active site of LinB is occupied by clindamycin (green) and the nonhydrolyzable ATP analog, AMPCPP (beige). One molecule of LinB is shown in blue (surface representation, right); the second copy of LinB is shown in gray. The model in PDB ID 3JZ0 was used to prepare this figure [114]. Nitrogen atoms are blue, and oxygen atoms are red in CLI.