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Tolerability and efficacy of long-term treatment with daptomycin, ceftazidime and colistin in a patient with a polymicrobial, multidrug-resistant prosthetic joint reinfection: a case report
© Pasticci et al.; licensee BioMed Central Ltd. 2014
Received: 16 September 2013
Accepted: 1 April 2014
Published: 12 June 2014
Prosthetic joint infections are severe complications of joint implants. Further complications arise when polymicrobial and/or multidrug-resistant microorganisms are involved. Currently, there are limited data on the management of these infections and on the tolerability of long-term treatment with daptomycin, ceftazidime and colistin.
A 55-year-old Caucasian woman who had a right hip prosthesis removed 1 year prior because of infection was admitted for prosthesis reimplantation. On admission at our hospital, anamnesis regarding etiology and management of prosthesis infection was not available. On clinical, laboratory findings and imaging studies infection was not suspected. A hip prosthesis was reimplanted. At surgery, histopathological and microbiological investigations were not taken. Three weeks after reimplantation, surgical site infection due to Enterobacter cloacae was diagnosed and oral ciprofloxacin was prescribed. Four days later, a periprosthesis fluid collection was evidenced and a percutaneous needle aspirate grew Staphylococcus epidermidis and S. haemolyticus. Enterobacter genome was also detected from the same sample. Teicoplanin and meropenem were added to ciprofloxacin without clinical improvement. Moreover, acetabular cup dislocation was documented. She underwent prosthesis explantation, debridement, and positioning of an antimicrobial mixed spacer. From the intraoperatory cultures S. epidermidis and Acinetobacter baumannii were grown. Daptomycin, ceftazidime, colistin and rifampin were administered. Four days later, rifampin was stopped due to a suspected liver toxicity. While undergoing therapy she presented recurrent episodes of wound dehiscence and on the 22nd week of treatment a further surgical debridement was performed, upon which the spacer was removed. At this time, intraoperative cultures resulted negative. Three months later, after a total of 8 months, antimicrobials were interrupted. Subsequently, a femoral transcondylar traction was positioned, and 3 weeks later a new prosthesis was reimplanted. At over 1 year after reimplantation she is well.
Our findings suggest that microbiologic investigations are mandatory even when prosthetic joint infection is not suspected. Molecular methods for identification of microorganisms can be used in addition to conventional cultures especially when patients are under antibiotic treatment. Daptomycin, ceftazidime and colistin can be administered for several months without side effects. Guidelines specifically addressing the diagnosis and the management of polymicrobial, multidrug-resistant prosthetic joint infections need to be developed.
Prosthetic joint infection (PJI) is one of the most severe complications of joint replacement . Although this is a rare event , the overall burden is high as a consequence of an increased number of implanted prosthesis in the aging population, an increased number of patients with risk factors for infection and improved methods to detect these infections. PJIs are associated with high morbidity, a need of complex treatment, prolonged hospitalization and substantial healthcare costs. Moreover, PJIs can lead to impaired functioning or even permanent disability [1, 2]. Further complications arise when polymicrobial, multi-drug-resistant (MDR) [3, 4] or difficult to treat microorganisms are involved [5–10].
Here, a complicated case of PJ reinfection is reported.
This article reports a polymicrobial, MDR prosthesis reinfection successfully treated with a two-stage long interval reimplant and prolonged antimicrobial therapy.
In our case, E. cloacae, A. baumannii and CoNS were the more probable etiologies of the infection. In fact, all the microorganisms, even in different combinations and at different times, were identified from multiple intraoperative tissues, prosthesis, and periprosthesis and synovial fluid aspirates [14–16]. It is impossible to state if any of the isolated microorganisms had already been present in a nonreplicating phase in the involved articulation at the time of the first reimplantation at our hospital. Nonperforming intraoperative histopathological and microbiological examinations can lead to missed cases of prosthesis infections [2, 5, 14–16]. Improper sample collection, small colony variants [7, 8], antimicrobial therapy before or during surgery and a lack of sonication [17–19] can also hinder diagnosis and etiology of PJIs [1, 2, 5, 13–20]. Small colony variants as well can lead to problems in microorganism identification and antimicrobial susceptibility results [7, 8]. However, in our case, it was not possible to verify if the observed differences for CoNS in respect to susceptibility and identification results were due to small colony variants.
The SeptiFast test has been commercialized for the diagnosis of sepsis from peripheral blood samples and identifies 25 different common pathogens . This test has been suggested to have a potentiality in detecting pathogens also from specimens other than blood, like sonicated fluids from removed prosthesis and synovial fluids [19, 22]. Its sensitivity was better than that of culture in patients under antibiotic treatment . In our case Enterobacter cloacae/aerogenes and CoNS genomes were detected with the SeptiFast test in the aspirated periprosthetic fluid, and contemporary cultures grew S. epidermidis and S. haemolyticus. At that time, the patient had been diagnosed surgical site infection and was on oral ciprofloxacin, active in vitro against E. cloacae but not against CoNS. The clinical significance of deoxyribonucleic acid (DNA) in the blood of septic patients in the absence of microorganism growth is still not optimally defined  and there is limited data on other biological samples. However, in our case, the fact that, 8 days later, E. cloacae was isolated from the aspirated synovial fluid points to the clinical relevance of the molecular results. The absence of bacterial DNA and viable microorganisms in intraoperative samples at the time the prosthesis was implanted for the third time was used to further support the absence of residual infection. Culture has the ability to identify microorganisms not included in the SeptiFast panel and to allow susceptibility testing. Thus, it is reasonable to use a molecular test in adjunct to culture in patients with PJIs under antibiotic therapy.
Regarding the most effective surgical strategy for PJIs and the best time of prosthesis reimplantation, the decision depends on the operating orthopedic surgeon, medical specialists, and the patient . Concerning the use of spacers, some researchers recommend avoiding cement spacers when infections are due to MDR or difficult to treat microorganisms such as quinolone-resistant and rifampin-resistant staphylococci, quinolone-resistant Gram-negative microorganisms, small colony variants, or fungi [5–8, 16, 20]. However, other researchers suggest avoiding external fixations in the presence of bone infection, but instead perform debridement repeatedly and change spacers as necessary. Furthermore, antimicrobial impregnated spacers, either premixed or prepared by the surgeons, can cause systemic toxicity . The optimal timing for prosthesis reimplantation is another issue lacking controlled randomized studies to support a specific recommendation . In our patient, initially, a cement spacer was positioned, then, it was removed and for a 3-month interval our patient was left without a spacer, continuing intravenous antimicrobial therapy. Then, after a long interval without antimicrobials, clinical signs of infection and normal ESR and C-RP results, she was readmitted for reimplantation. Overall, in our patient there was a delay of 1 year between prosthesis explant and reimplantation, due to the fact that: 1) clinically, the infection was not fully controlled until the spacer was left in place, 2) the patient had undergone hip prosthesis surgery twice and was at high risk for further infective complications.
In our case, recovery from infection was obtained with surgical therapy and a combination of antimicrobial treatment with daptomycin, ceftazidime, and colistin that were finally efficacious and well tolerated. It is possible that initial antibiotic therapy with teicoplanin, ceftazidime and ciprofloxacin was not completely effective due to biofilm infection, suboptimal dosing of teicoplanin, and resulting CoNS ciprofloxacin resistance.
Our findings suggest that microbiologic investigations are mandatory even when PJI is not suspected on clinical and laboratory findings and imaging studies. Molecular methods for identification of microorganisms can be used in addition to conventional cultures in patients with PJIs especially when they are under antibiotic treatment. Daptomycin, ceftazidime and colistin can be administered for several months without side effects. Guidelines specifically addressing the diagnosis and the management of polymicrobial, MDR PJIs need to be developed.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
We would like to thank the patient for her consent to report the case and accompanying images.
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