Advances In Antibiotic Resistance Of P.acnes

Propionibacterium acnes (P. acnes) is a rod-shaped, spore-free, flagellate-free, Gram-positive anaerobic bacterium that resides mainly in the skin, gastrointestinal tract, and genitourinary tract. It is an opportunity. The pathogen is closely related to acne. P. acnes secretes a variety of substances (proteases, lipases, porphyrins, etc.) directly involved in the development of acne; it can also release IL-1, TNF-α, IL-8, IL-12 and the body through the Toll-like receptor pathway. Proinflammatory cytokines such as IFN-γ are involved in the inflammation and immune response of acne. P. acnes can effectively control and treat acne by inhibiting or killing P. acnes. However, due to the long-term and repeated use of antibiotics in acne treatment, drug resistance P. acnes is widespread worldwide and even forms cross-resistance. This article reviews the antibiotic resistance of P. acnes to attract people’s attention and find effective measures to reduce the production of P. acnes resistant strains.

1 P. acnes antibiotic resistance trend

1. 1 Historical progress in the treatment of acne with antibiotics

In 1896, the German dermatologist Unna first proposed the existence of P. acnes and established the relationship between acne and local P. acnes infection. But then P. acnes was also isolated from normal healthy skin, and its theory of pathogens was once questioned until Kirschbaum and Kligman reaffirmed the involvement of P. acnes in 1963 and played an important role in it in 1963. The relationship between P. acnes and acne has regained people’s attention, and antibiotic treatment of acne has gradually been accepted with human understanding of P. acnes. Antibiotic treatment for acne began in the early 1950s with macrolide antibiotics, which can penetrate into the funnel of the hair follicle sebaceous glands, inhibiting the neutrophil chemotaxis while reducing the number of P. acnes. Reduces the inflammatory response caused by P. acnes. Erythromycin, clindamycin and tetracycline were the main oral drugs, and then doxycycline and minocycline were also used for the treatment of acne and achieved good results. In the mid-1970s, it was found that topical antibiotics were safe, effective and convenient for the treatment of acne. Then the topical antibiotics based on erythromycin, clindamycin and metronidazole quickly became the treatment of acne, especially for acne. Inflammatory skin lesions, local antibiotic treatment still occupies an important position.

1. 2 P. acnes Antibiotic resistance consequences

Drug resistance The production of P. acnes is a direct result of the non-standard use of antibiotics during the treatment of acne, and it is a difficult point in the treatment of acne. The antibiotic effect of acne is reduced, and the antibiotic treatment time is prolonged. On the one hand, the resistance of bacteria in other parts of the body is directly induced. On the other hand, the drug resistance gene is transferred to other bacteria through plasmid or phage, causing other drug-resistant bacteria to appear, changing the microbial group of humans. Increase the chances of other bacterial infections in the body, especially Staphylococcus aureus and Staphylococcus epidermidis. Some scholars have studied 105 patients with acne and found that 35% of them have received antibiotic treatment. Although there are no symptoms of upper respiratory tract infection, nearly 85% of group A hemolytic streptococcus in oral administration is resistant to tetracycline. A retrospective analysis of 118 496 patients with acne showed that the rate of upper respiratory tract infection was 2.15 times higher in patients with acne treated with antibiotics during the first year than those without antibiotics. These studies show that the emergence of drug resistance P. acnes is a serious problem facing humans, and people need to take effective measures to avoid further development of drug resistance.

1. 3 P. acnes Antibiotic resistance

1. 3. 1 Foreign P. acnes antibiotic resistance

P. acnes resistance begins with topical antibiotics for the treatment of acne, but no studies have directly indicated that this resistance is caused by topical antibiotics. Most studies still prefer long-term oral or topical antibiotics that are prone to drug resistance. The generation of acnes. The P. acnes strain of clacillin and erythromycin was first reported in 1979, and then in 1983 Leyden et al. found a tetracycline-resistant P. acnes strain. Since then, there have been reports of P. acnes resistance to common antibiotics in different regions. Studies have shown that in 1995 and 2005, the antibiotic resistance rate of P. acnes in acne patients in South Korea was low. However, in 2011, the re-drug resistance rate increased to 36.7%, and resistance to clindamycin and erythromycin was observed. The rates reached 30% and 26.7%, respectively, and there were different degrees of tetracycline, minocycline and doxycycline.
Resistance. A small sample study in France in 2001 showed that P. acnes resistance to erythromycin was 52%, and further studies on P. acnes resistance in 2010 found that erythromycin resistance rate was as high as 75.1%, tetracycline resistance rate It was 9.5%, and it was speculated that tetracycline-resistant bacteria were equally resistant to doxycycline. In the United Kingdom from 1999 to 2001, the resistance rate of P. acnes to one or more antibiotics was 34.5% to 55.5%. In Chile, the resistance rates of P. acnes to erythromycin and clindamycin in 2001 were 3.8% and 1.9%, respectively. In 2013, 80 strains of P. acnes were isolated from 83 lesions of acne patients. The drug susceptibility test showed that the resistance rate of P. acnes to erythromycin and clindamycin increased to 12.12% and 7.0%, and all strains were found to be resistant to methoxysulfonamides. Most studies abroad have shown that the number of resistant bacteria is increasing, mainly resistant to macrolide antibiotics, including tetracyclines and methoxypyrimidines.

1. 3. 2 P. acnes antibiotic resistance in parts of China

China’s P. acnes is also not optimistic about the resistance of common antibiotics to acne. Some researchers conducted P. acnes antibiotic-related experiments in 111 cases of acne patients in Hong Kong in China in 2011. The results showed that the detection rate of P. acnes was 77.5%, among which clindamycin, erythromycin, tetracycline, and more Both cyclin and minocycline were resistant to different degrees, and the resistance rates were 54.7%, 53.5%, 20.0%, 16.3%, and 16.3%, respectively, and drug resistance was found. Relevant to the duration of treatment. The analysis of P. acnes resistance in the lesions of acne patients in Wuhan showed that erythromycin resistance was the main factor, and the analysis may be closely related to the widespread use of macrolide antibiotics and clindamycin preparations in China. Mei et al.’s study on 236 cases of P. acnes antibiotic resistance showed that the infection rate of P. acnes was 32.4%, of which 122 strains were resistant to tinidazole, 103 strains were resistant to erythromycin, and 35 strains were resistant to tetracycline. Drug, no resistance to minocycline, suggesting that minocycline is sensitive to P. acnes; Sun Fei et al. P. acnes analysis of resistance to macrolides and tetracyclines showed P. acnes The resistance rates to erythromycin, azithromycin and clarithromycin were 30.13%, 48.72%, 81.77%, respectively, sensitive to tetracycline, minocycline and doxycycline, and within three macrocycles. Cross-resistance of ester antibiotics is related to the clinical abuse of macrolides, and cross-resistance is related to drug structure. Although there are differences in antibiotic resistance among P. acnes in various regions at home and abroad, there is an overall upward trend. Analysis of the reasons for this difference may be closely related to the use of antibiotics, the combination of topical drugs, the sampling and culture methods of bacteria, and even the subtypes of bacteria.

2 P. acnes antibiotic resistance mechanism

Bacterial antibiotic resistance is defined as the minimum inhibitory concentration in vitro that exceeds the serum drug concentration in vivo. Long-term topical or systemic oral antibiotics for acne treatment may lead to the emergence of drug-resistant strains, especially those with long course of treatment, poor efficacy, relapse of disease, poor medication compliance and immunodeficiency. P. acnes antibiotic resistance is associated with chromosome mutations or by the transfer of plasmids, transposons or phage-mediated resistance genes. At the same time, P. acnes is also related to the type of strain and the formation of bacterial biofilm.

2. 1 Chromosomal mutation or transfer of drug resistance genes

The study found that P. acnes can be resistant to macrolides, tetracyclines, quinolones, and methoxypyrimidines through chromosomal mutations or drug-resistant gene transfer. The resistance to erythromycin/clindamycin is dominated by 23S rRNA point mutations, especially the V region point mutations of the 23S rRNA domain, including GT and AG mutations, which are common with AG mutations; more in-depth studies have also found that AG mutations at different loci in this region lead to different antibiotic resistance, 2058 AG mutations are associated with erythromycin resistance, and 2059 AG mutations are associated with cross-resistance of erythromycin and clindamycin, while erm ( The presence of the transposon of X) confers resistance to all macrolide antibiotics. The resistance of P. acnes to tetracyclines is mainly mediated by a single GC base exchange in 16S rRNA (equivalent to 1058 bases in E. coli); studies have also found two genes encoding tetracycline resistance, among which The tetracycline K and L genes encode active transporters that transport the drug out of the cell by active transport, resulting in tetracycline resistance, while the M and O genes encode ribosome-protected proteins and induce resistance to minocycline, suggesting Tetracycline and minocycline may cause cross-resistance. Some scholars have found that the substitution of partial amino acids in P. acnes DNA gyrase and DNA topoisomerase is the main mechanism of quinolone resistance. P. acnes is relatively less resistant to methoxypyrimidine drugs, possibly by producing a modified form of dihydrofolate reductase that encodes resistance to trimethoprim-sulfamethoxazole on the plasmid.

2. 2 P. acnes type and drug resistance

For P. acnes single, multi-site and whole genome sequence (WGS) analysis, P. acness is divided into types I, II and III, each type is divided into multiple subtypes, and the relationship with acne is closely related to I. Types include IA (IA-1IA-2), IB (IB-1, IB-2, IB-3) and IC types. McDowell’s genetic analysis of P. acnes pathogenicity, symbiosis, and antibiotic resistance found that IA is closely related to acne, and IB, II, and III strains are more frequently associated with blood, soft tissue, and medical implant-related infections. The data further showed that 85% of the resistant isolates belonged to the I-A1 type, and all types of IC isolates were resistant to tetracyclines due to the 16S rRNA mutation. There are also differences in the types of strains infected by acne patients in different regions. In the United States and Greece, only one type of IB (PRP-102) and one type II (PRP-047) isolates were isolated and identified from acne patients, PRP- 102 is resistant to all antibiotics, while PRP-047 is resistant only to erythromycin and clindamycin. Therefore, the type of P. acnes has a certain relationship with the production of antibiotic resistance. However, the large accumulation of P. acnes in the hair follicle may be related to the formation of biofilm, and the biofilm itself will increase the antibiotic resistance, so it is speculated that P. The formation of acnes biofilms may also be associated with antibiotic resistance.

2. 3 P. acnes biofilm formation and antibiotic resistance

The formation of P. acnes biofilms may play an important role in the development of drug resistance. Biofilms have three essential ingredients: microbial cells, cell adhesion surfaces, and extracellular polymeric matrices. The presence of bacterial biofilms allows bacteria to intercalate into colonies and form a protective outer skeleton on the surface to act as a physical barrier to affect and prevent the treatment of various antimicrobial agents. The current research has confirmed that P. acnes can form biofilms in prosthetic hip joints, various orthopedic biological materials and intervertebral discs, leading to unhealed infection. By establishing an in vitro biofilm model of P. acnes, Jahns et al. found that the extracellular polymeric (EPS) matrix of biofilms consists of cellular DNA, proteins, and glycosyl residues, and that biofilm cells are found to be stress-inducible genes and coding potentials. Virulence-related CAMP factor levels are up-regulated and can produce persistent cells that produce reversible tolerance to 50-fold MIC of conventional antibiotics. Other studies have shown that the formation of P. acnes biofilm may provide a new growth environment for S. aureus. However, these studies show that P. acnes biofilms are formed on the surface of in vitro or implanted prostheses. The current evidence is that there is insufficient biofilm formation in acne lesions, and Burkhart et al believe that P. acnes biofilms exist. Within the hair follicle sebaceous gland unit, it is speculated that the failure of antibiotic treatment in patients with acne vulgaris may be related to the high resistance of bacteria to antibiotics in the presence of biofilm.

3 Measures to reduce drug resistance P. acnes

P. acnes antibiotic resistance mechanism is complex, in addition to the above factors, whether it is related to the host gene polymorphism needs further study, but the upward trend of drug resistance rate is not optimistic, in the depth of research on resistance mechanisms must be active Effective measures to reduce the production of drug resistance P. acnes. These include the standardized use of antibiotics in the treatment of acne, the development of new drugs and the monitoring of drug resistance in various regions. Among them, the study of P. acnes resistance in various regions, clinicians can choose according to the characteristics of antibiotic resistance in the region