Lincomycin

BackgroundThe intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment.MethodsTo assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of antibiotic-treated mice, stool samples were analyzed using quantitative real-time polymerase chain reaction to assess changes in the microbiota and using non-targeted metabolic profiling. To assess whether the findings were applicable to another antibiotic class that suppresses intestinal anaerobes, similar experiments were conducted with piperacillin/tazobactam.ResultsColonization resistance began to recover within 5 days and was intact by 12 days after clindamycin treatment, coinciding with the recovery bacteria from the families Lachnospiraceae and Ruminococcaceae, both part of the phylum Firmicutes. Clindamycin treatment caused marked changes in metabolites present in fecal specimens. Of 484 compounds analyzed, 146 (30%) exhibited a significant increase or decrease in concentration during clindamycin treatment followed by recovery to baseline that coincided with restoration of in vivo colonization resistance. Identified as potential biomarkers of colonization resistance, these compounds included intermediates in carbohydrate or protein metabolism that increased (pentitols, gamma-glutamyl amino acids and inositol metabolites) or decreased (pentoses, dipeptides) with clindamycin treatment. Piperacillin/tazobactam treatment caused similar alterations in the intestinal microbiota and fecal metabolites.ConclusionsRecovery of colonization resistance after antibiotic treatment coincided with restoration of several fecal bacterial metabolites. These metabolites could provide useful biomarkers indicating intact or disrupted colonization resistance during and after antibiotic treatment.

BackgroundStaphylococcal species account for more than 50% of periprosthetic joint infections (PJI) and antimicrobial therapy with rifampin-based combination regimens has been shown effective. The present study evaluates the safety and efficacy of clindamycin in combination with rifampin for the management of staphylococcal PJI.MethodsIn this retrospective cohort study, patients were included who received clindamycin-rifampin combination therapy to treat a periprosthetic hip or knee infection by Staphylococcus aureus or coagulase-negative staphylococci. Patients were treated according to a standardized treatment algorithm and followed for a median of 54 months. Of the 36 patients with periprosthetic staphylococcal infections, 31 had an infection of the hip, and five had an infection of the knee. Eighteen patients underwent debridement and retention of the implant (DAIR) for an early infection, the other 18 patients underwent revision of loose components in presumed aseptic loosening with unexpected positive cultures.ResultsIn this study, we report a success rate of 86%, with five recurrent/persistent PJI in 36 treated patients. Cure rate was 78% (14/18) in the DAIR patients and 94% (17/18) in the revision group. Five patients (14%) discontinued clindamycin-rifampin due to side effects. Of the 31 patients completing the clindamycin-rifampin regimen 29 patients (94%) were cured.ConclusionCombined therapy with clindamycin and rifampin is a safe, well tolerated and effective regimen for the treatment of staphylococcal periprosthetic infection.

ObjectiveTo compare flucloxacillin with clindamycin to flucloxacillin alone for the treatment of limb cellulitis.DesignParallel, double-blinded, randomised controlled trial.SettingEmergency department attendances and general practice referrals within 20 hospitals in England.InterventionsFlucloxacillin, at a minimum of 500 mg 4 times per day for 5 days, with clindamycin 300 mg 4 times per day for 2 days given orally versus flucloxacillin given alone.Main outcome measuresThe primary outcome was improvement at day 5. This was defined as being afebrile with either a reduction in affected skin surface temperature or a reduction in the circumference of the affected area. Secondary outcomes included resolution of systemic features, resolution of inflammatory markers, recovery of renal function, reduction in the affected area, decrease in pain, return to work or normal activities and the absence of increased side effects.Results410 patients were included in the trial. No significant difference was seen in improvement at day 5 for flucloxacillin with clindamycin (136/156, 87%) versus flucloxacillin alone (140/172, 81%)-OR 1.55 (95% CI 0.81 to 3.01), p=0.174. There was a significant difference in the number of patients with diarrhoea at day 5 in the flucloxacillin with clindamycin allocation (34/160, 22%) versus flucloxacillin alone (16/176, 9%)-OR 2.7 (95% CI 1.41 to 5.07), p=0.002. There was no clinically significant difference in any secondary outcome measures. There was no significant difference in the number of patients stating that they had returned to normal activities at the day 30 interview in the flucloxacillin with clindamycin allocation (99/121, 82%) versus flucloxacillin alone (104/129, 81%)-adjusted OR 0.90 (95% CI 0.44 to 1.84).ConclusionsThe addition of a short course of clindamycin to flucloxacillin early on in limb cellulitis does not improve outcome. The addition of clindamycin doubles the likelihood of diarrhoea within the first few days.Trial registration numberNCT01876628, Results.

Due to increasing antimicrobial resistance and side effects caused by current standard antimicrobial regimens used for treatment of prosthetic joint infection (PJI), alternative options are urgently needed. We aimed to investigate the effect of clindamycin in different exposure strategies against Staphylococcus aureus in an in vitro mature biofilm model. In short, 7-day biofilms were generated on polystyrene plates and titanium-aluminum-vanadium discs using a clinical S. aureus PJI isolate. Next, biofilms were exposed to clindamycin according to four strategies: single 24-h exposure; prolonged 48- or 72-h exposure; repeated 24-h exposures during a 4-day period, and sequential exposures of initial 24-h rifampicin-based therapy followed by 24-h exposure to clindamycin. The remaining bacterial load (colony-forming unit [CFU]/mL) after antibiotic exposure was assessed. Confocal laser scanning and atomic force microscopy were applied to evaluate the biofilm structure. Single exposure to clindamycin for 24 h or prolonged up to 72 h did not result in any relevant reduction in bacterial load. Repeated 24-h exposures demonstrated relevant reductions of >3 log CFU/mL at clindamycin concentrations ≥16 mg/L for the 3rd and 4th consecutive doses. Sequential rifampicin-ciprofloxacin combination exposure followed by clindamycin showed bacterial load reductions of 3- to 4-log CFU/mL, similar to continued rifampicin-ciprofloxacin exposure. This was achieved for concentrations equivalent to levels achieved after standard dosing of clindamycin in clinical practice. These experimental findings support that clindamycin monotherapy is not an optimal choice when starting antimicrobial treatment of PJI but that later on, rifampicin may be safely switched to clindamycin in patients with PJI who do not tolerate prolonged rifampicin-based treatment.ImportanceRifampicin-in combination with another antibiotics-is recommended in all guidelines as first choice treatment of prosthetic joint infections (PJIs), despite adverse interactions and side effects associated with this antibiotic. In a search for alternative approaches, the switch to clindamycin in patients after rifampicin-based antibiotic treatment was found to be effective in some recent observational clinical studies. In our in vitro study, we determined the effect of clindamycin on Staphylococcus aureus in mature biofilms, to obtain further insight. Our study showed that clindamycin was effective in reducing mature biofilm-residing S. aureus after initial exposure to rifampicin-ciprofloxacin, while it was not effective as first treatment. These in vitro findings provide evidence for the hypothesis that rifampicin-ciprofloxacin can be successfully switched to clindamycin monotherapy in PJI patients in a later phase of treatment.