<i>Staphylococcus aureus</i>develops increased resistance to antibiotics by forming dynamic small colony variants during chronic osteomyelitis

Tuchscherr, Lorena; Kreis, Carolin; Hoerr, Verena; Flint, Lloyd D.; Hachmeister, M.; Geraci, Jennifer; Bremer-Streck, Sibylle; Kiehntopf, Michael; Medina, Eva; Kribus, M.; Raschke, Michael J.; Pletz, Mathias W.; Peters, Georg; Löffler, Bettina

doi:10.1093/jac/dkv371

Cited by 108 publications

(158 citation statements)

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“…For example, it is not known if a special antibiotic regimen induces and selects for CO 2 -dependent SCVs or as yet uncharacterized SCVs. Recent experimental research suggests that additional antimicrobial compounds, such as moxifloxacin and clindamycin, promote the formation of SCVs (33). For this review, 46 clinical studies dealing with SCVs were retrieved from the literature, spanning the time frame from 1951 to 2014 (Table 2).…”

Section: Clinical Infectionsmentioning

confidence: 99%

“…In particular, in bone tissue, bacterial persistence was observed for up to 2 months and was accompanied by a high rate of SCV formation (142). Antibiotic treatment with different compounds was always less effective in the chronic than in the acute stage of the infection (33). (vi) In contrast to systemic treatment, local treatment with high levels of antibiotics over a prolonged time was successfully tested in a chronic osteomyelitis model in rabbits (143).…”

Section: Animal Models For Studying the Formation And Persistence Of mentioning

confidence: 99%

“…In the context of antibiotic treatment of staphylococci in general, one should keep in mind that the administration of antibiotics itself may lead to the formation of SCVs (33). Respective phenotypic effects of antibiotic agents have been described since the earliest times of their use (7).…”

Section: Current and Future Treatment Regimensmentioning

confidence: 99%

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Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

2016

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SUMMARYSmall colony variants (SCVs) were first described more than 100 years ago forStaphylococcus aureusand various coagulase-negative staphylococci. Two decades ago, an association between chronic staphylococcal infections and the presence of SCVs was observed. Since then, many clinical studies and observations have been published which tie recurrent, persistent staphylococcal infections, including device-associated infections, bone and tissue infections, and airway infections of cystic fibrosis patients, to this special phenotype. By their intracellular lifestyle, SCVs exhibit so-called phenotypic (or functional) resistance beyond the classical resistance mechanisms, and they can often be retrieved from therapy-refractory courses of infection. In this review, the various clinical infections where SCVs can be expected and isolated, diagnostic procedures for optimized species confirmation, and the pathogenesis of SCVs, including defined underlying molecular mechanisms and the phenotype switch phenomenon, are presented. Moreover, relevant animal models and suggested treatment regimens, as well as the requirements for future research areas, are highlighted.

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Section: Clinical Infectionsmentioning

confidence: 99%

Section: Animal Models For Studying the Formation And Persistence Of mentioning

confidence: 99%

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Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

2016

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“…These studies also showed an association between presence of SCV S. aureus and more rapid pulmonary decline. Small‐colony variant formation also occurs in MRSA but has only been reported in few cases in CF and non‐CF …”

Section: Virulencementioning

confidence: 99%

Biology and management of methicillin resistantStaphylococcus aureusin cystic fibrosis

Akil

Muhlebach

2018

Pediatric Pulmonology

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Staphylococcus aureus is one of the earliest bacteria isolated from the respiratory tract in people with cystic fibrosis (CF). Its methicillin resistant form, MRSA, has gained attention due to the rapid increase in the last decades and worse outcomes with chronic infection. In the United States, prevalence of MRSA in CF is around 27%, but is much lower (3-18%) in most other countries. Methicillin is typically genetically encoded by the mecA gene, which encodes for an alternative penicillin binding protein (PRBa). This PRBa has low affinity to β-lactams, thereby enabling growth of S. aureus in the presence of penicillinase resistant penicillins and most other β-lactams. Non-mecA positive strains of MRSA, so-called borderline resistant (BORSA) have also been described. In addition to production of toxins, the virulence of S. aureus is conferred by its adaptability allowing persistence in face of antibiotic therapies and host defense. These adaptive growth mechanisms include small colony variants, biofilms, and growth under anaerobic conditions. Several reports have described successful eradication of MRSA, yet only two randomized trials of eradication during early infection have been conducted. A list of MRSA specific antibiotics with dosing relevant to CF patients is presented here. Many of these require special dosing in people with CF. Novel antibiotics are in trials for skin and soft tissue infections and it is unclear if and when those might be available for lung infections. Thus the best strategies for MRSA would be primary prevention.

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“…Recent reports have shown that resistance developed during treatment in initially susceptible S. aureus can also be related to dynamic small colony variants. Some antibiotics like clindamycin, moxifloxacin and gentamicin can even induce the latter [47,48] .…”

Section: Antibiotic Treatmentmentioning

confidence: 99%

New Antibiotics in the Therapy of Osteomyelitis

Hirsiger¹,

Ilgaz²,

Uçkay³

2018

mjima

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Staphylococcus aureusdevelops increased resistance to antibiotics by forming dynamic small colony variants during chronic osteomyelitis

Abstract: In all infection models rifampicin was most effective at reducing bacterial loads. In the chronic stage, particularly in the in vivo model, many tested compounds lost activity against persisting bacteria and some antibiotics even induced SCV formation.

Cited by 108 publications

References 50 publications

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

Biology and management of methicillin resistantStaphylococcus aureusin cystic fibrosis

New Antibiotics in the Therapy of Osteomyelitis

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