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1.  Sonication of antibiotic-loaded cement spacers in a two-stage revision protocol for infected joint arthroplasty 
Culturing of the sonication fluid of removed implants has proven to be more sensitive than conventional periprosthetic tissue culture for the microbiological diagnosis of prosthetic joint infection. Since bacteria surviving on antibiotic-loaded cement spacers used in a two-stage exchange protocol for infected arthroplasties may cause the persistence of infection, in this study we asked whether the sonication also could be used to identify bacteria on antibiotic-loaded cement spacers removed at the second surgical stage during a two-stage exchange procedure to confirm whether or not the prosthetic joint infection had been eradicated.
We cultured the sonication fluid of cement spacers that had been originally implanted in a two-stage exchange protocol in 21 patients (mean age, 66 years) affected by prosthetic joint infection (16 total knee prostheses and 5 hip prostheses). The cement spacers were vortexed for 30 seconds and then subjected to sonication (frequency 35–40 KHz). The resulting sonicate fluid was cultured for aerobic and anaerobic bacteria.
The sonication fluid culture of the removed spacer was positive in six patients (29%), with isolation of methicillin-sensible Staphylococcus Aureus (MSSA) in three cases, methicillin-resistant Staphylococcus Aureus (MRSA) in one case and Pseudomonas Aeruginosa in two cases. In three of these positive cases, the traditional culture of periprosthetic tissue was negative. Two patients with positive sonication culture of the spacer were successfully treated by early debridement of the revision prosthesis and systemic antibiotic therapy. In three patients a knee arthrodesis was planned and performed as the second surgical stage. In two of them the infection was caused by highly resistant Pseudomonas Aeruginosa. The other patient with a MSSA infection had been poorly compliant with the systemic antibiotic therapy due to her mental impairment. The patient originally affected by MRSA infection of his primary hip arthroplasty developed recurrent infection of his revision prosthesis and eventually underwent Girdlestone arthroplasty.
The sonication culture can be used to discover any bacteria on the antibiotic-loaded cement spacer during a two-stage exchange protocol, thus permitting the adoption of timely treatment options, such as the early prosthetic debridment.
PMCID: PMC3693994  PMID: 24192225
Prosthesis-related infections; Sonication; Bone cements; Treatment outcome; Microbial biofilm
2.  Pathogen-driven decision for implant retention in the management of infected total knee prostheses 
International Orthopaedics  2013;37(8):1471-1475.
In prosthetic joint infections (PJIs) of the knee, debridement with implant retention is associated with a high risk of recurrence.
A single-centre cohort study was performed with extensive analysis of the literature covering 1980–2012.
In 21 patients (mean age 80.4 years, 19 immunosuppressed), in association with 1.5–three months of antibiotic treatment, an attempt was made to salvage the prosthesis by open (11 patients) or arthroscopic (ten patients) debridement. After a mean follow-up of seven years (range four–20 years), patients were in remission in seven cases (33 %). Remission was achieved in 0 % of all methicillin-resistant Staphylococcus aureus (MRSA) infections (zero/three), in 0 % (zero/three) of methicillin-resistant coagulase-negative staphylococcal infections, in 29 % (two/seven) of methicillin-sensitive S. aureus infections and in 75 % (three/four) of infections due to streptococci. The literature review focused on implant preserving approaches yielded 599 cases with an overall success rate of 47 % (284/599) and significantly more remissions in streptococcal vs staphylococcal knee PJIs (43/54 vs 144/324; p < 0.01, odds ratio 4.9, 95 % confidence interval 2.4–10.9).
In addition to established indications for explantation such as implant loosening, sinus tract or methicillin resistance, the decision for debridement and retention of knee PJIs should also depend on the pathogen. Implant preservation is futile with methicillin-resistant staphylococci, but seems to be a valid option for streptococcal PJIs.
PMCID: PMC3728396  PMID: 23695880
3.  Linezolid plus Rifampin as a Salvage Therapy in Prosthetic Joint Infections Treated without Removing the Implant▿ 
The aim of this study is to describe our experience with linezolid plus rifampin as a salvage therapy in prosthetic joint infections (PJIs) when other antibiotic regimens failed or were not tolerated. A total of 161 patients with a documented prosthetic joint infection were diagnosed with a PJI and prospectively followed up from January 2000 to April 2007. Clinical characteristics, inflammatory markers, microbiological and radiological data, and antibiotic treatment were recorded. After a 2-year follow-up, patients were classified as cured when the prosthesis was not removed, symptoms of infection disappeared, and inflammatory parameters were within the normal range. Any other outcome was considered a failure. The mean age of the entire cohort (n = 161) was 67 years. Ninety-five episodes were on a knee prosthesis (59%), and 66 were on a hip prosthesis (41%). A total of 49 patients received linezolid plus rifampin: 45 due to failure of the previous antibiotic regimen and 4 due to an adverse event associated with the prior antibiotics. In no case was the implant removed. The mean (standard deviation) duration of treatment was 80.2 (29.7) days. The success rate after 24 months of follow-up was 69.4% (34/49 patients). Three patients developed thrombocytopenia and 3 developed anemia; however, it was not necessary to stop linezolid. Linezolid plus rifampin is an alternative salvage therapy when the implant is not removed.
PMCID: PMC3165328  PMID: 21690277
4.  A Retrospective Review of the Clinical Experience of Linezolid with or Without Rifampicin in Prosthetic Joint Infections Treated with Debridement and Implant Retention 
Infectious Diseases and Therapy  2014;3(2):235-243.
Debridement and prosthesis retention, combined with a prolonged antibiotic regimen including rifampicin, is an accepted therapeutic approach when the duration of symptoms is less than 4 weeks and there are no radiological signs of loosening. The outcome of patients managed with this strategy has been previously assessed in several articles with success rates of 60–90%. This study aims to review the clinical experience with linezolid in 3 different hospitals from Spain and France in patients with prosthetic joint infection (PJI) managed with debridement, retention of the implant and treated with linezolid with or without rifampicin.
Patients with an acute PJI who underwent open debridement with implant retention treated with linezolid for more than 7 days in 3 hospitals from Barcelona, Tours and Lille between 2005 and 2011 were retrospectively reviewed. Relevant information about demographics, co-morbidity, type of implant, surgical treatment, microorganism isolated, antimicrobial therapy, adverse events (AEs) and outcomes were recorded from patients.
A total of 39 patients were retrospectively reviewed. The mean age (SD) was 70.5 (8.8) years and 9 patients had diabetes mellitus (23%). There were 25 (64%) knee prostheses, 13 (33%) hips and 1 shoulder (3%). The median interquartile range (IQR) days from arthroplasty to infection diagnosis was 17 (19–48) and 33 (85%) cases were diagnosed within the first 60 days. The median (IQR) duration of antibiotic treatment was 70.5 (34–96) days and the median (IQR) number of days on linezolid treatment was 44.5 (30–81). AEs were observed in 15 patients (38%), with gastrointestinal complaints in 8 cases and anemia in 5 being the most frequent. After a median (IQR) follow-up of 2.5 (1.8–3.6) years, there were 11 failures (28%) (8 relapses and 3 new infections). The failure rate was higher in the rifampicin group (36% vs. 18%) mainly due to a higher relapse rate (27% vs. 12%) although differences were not statistically significant.
Management of acute PJIs with debridement and retention of the implant linezolid, with or without rifampicin, is associated with a high remission rate and it is an alternative treatment for infections due to fluoroquinolone and/or rifampicin-resistant staphylococci.
Electronic supplementary material
The online version of this article (doi:10.1007/s40121-014-0032-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4269635  PMID: 25139552
Debridement; Infectious diseases; Linezolid; Prosthetic joint infection; Rifampicin; Treatment outcome
5.  Targeted Use of Vancomycin as Perioperative Prophylaxis Reduces Periprosthetic Joint Infection in Revision TKA 
The role of vancomycin in surgical antimicrobial prophylaxis and high-risk patients who are most likely to benefit remains unclear.
We determined the impact of targeted use of vancomycin on (1) the incidence of periprosthetic joint infection (PJI); and (2) the incidence of PJI from methicillin-resistant organisms in patients undergoing revision total knee arthroplasty (TKA) at our institution.
In an effort to reduce PJI rates, we added vancomycin to cefazolin as surgical antimicrobial prophylaxis for patients undergoing revision TKA in October 2010. Internal data indicated a high rate of PJI in revision TKA and in particular PJI resulting from methicillin-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). We retrospectively reviewed infection control surveillance data on 414 revision TKAs performed between July 2008 and June 2012 (fiscal years 2009–2012).
The overall rate of PJI in fiscal years 2009–2010 among 190 patients undergoing revision TKA was 7.89%. After the change in surgical antimicrobial prophylaxis, there was a significant reduction in PJI among patients undergoing revision TKA in fiscal years 2011–2012 to 3.13% (p = 0.046). In particular, we observed a reduction in PJI resulting from methicillin-resistant organisms over this same time period, from 4.21% to 0.89% (p = 0.049).
Targeted use of vancomycin in patients undergoing revision TKA was effective in reducing the rate of PJI and PJI resulting from methicillin-resistant organisms in an institution with a high baseline rate of PJI due to MRSA and MRSE. Identification of high-risk subgroups of patients within a surgical population can help target infection prevention strategies to those who are most likely to benefit and thus minimize potential risks (eg, selection of resistant organisms, adverse drug events) associated with broader application of such an intervention.
Level of Evidence
Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3889430  PMID: 23645338
6.  Rifampin Combination Therapy for Nonmycobacterial Infections 
Clinical Microbiology Reviews  2010;23(1):14-34.
Summary: The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.
PMCID: PMC2806656  PMID: 20065324
7.  Geographic Distribution of Staphylococcus aureus Causing Invasive Infections in Europe: A Molecular-Epidemiological Analysis 
PLoS Medicine  2010;7(1):e1000215.
Hajo Grundmann and colleagues describe the development of a new interactive mapping tool for analyzing the spatial distribution of invasive Staphylococcus aureus clones.
Staphylococcus aureus is one of the most important human pathogens and methicillin-resistant variants (MRSAs) are a major cause of hospital and community-acquired infection. We aimed to map the geographic distribution of the dominant clones that cause invasive infections in Europe.
Methods and Findings
In each country, staphylococcal reference laboratories secured the participation of a sufficient number of hospital laboratories to achieve national geo-demographic representation. Participating laboratories collected successive methicillin-susceptible (MSSA) and MRSA isolates from patients with invasive S. aureus infection using an agreed protocol. All isolates were sent to the respective national reference laboratories and characterised by quality-controlled sequence typing of the variable region of the staphylococcal spa gene (spa typing), and data were uploaded to a central database. Relevant genetic and phenotypic information was assembled for interactive interrogation by a purpose-built Web-based mapping application. Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 countries collected 2,890 MSSA and MRSA isolates from patients with invasive S. aureus infection. A wide geographical distribution of spa types was found with some prevalent in all European countries. MSSA were more diverse than MRSA. Genetic diversity of MRSA differed considerably between countries with dominant MRSA spa types forming distinctive geographical clusters. We provide evidence that a network approach consisting of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of MRSA populations such as early signalling of emerging strains, cross border spread, and importation by travel.
In contrast to MSSA, MRSA spa types have a predominantly regional distribution in Europe. This finding is indicative of the selection and spread of a limited number of clones within health care networks, suggesting that control efforts aimed at interrupting the spread within and between health care institutions may not only be feasible but ultimately successful and should therefore be strongly encouraged.
Please see later in the article for the Editors' Summary
Editors' Summary
The bacterium Staphylococcus aureus lives on the skin and in the nose of about a third of healthy people. Although S. aureus usually coexists peacefully with its human carriers, it is also an important disease-causing organism or pathogen. If it enters the body through a cut or during a surgical procedure, S. aureus can cause minor infections such as pimples and boils or more serious, life-threatening infections such as blood poisoning and pneumonia. Minor S. aureus infections can be treated without antibiotics—by draining a boil, for example. Invasive infections are usually treated with antibiotics. Unfortunately, many of the S. aureus clones (groups of bacteria that are all genetically related and descended from a single, common ancestor) that are now circulating are resistant to methicillin and several other antibiotics. Invasive methicillin-resistant S. aureus (MRSA) infections are a particular problem in hospitals and other health care facilities (so-called hospital-acquired MRSA infections), but they can also occur in otherwise healthy people who have not been admitted to a hospital (community-acquired MRSA infections).
Why Was This Study Done?
The severity and outcome of an S. aureus infection in an individual depends in part on the ability of the bacterial clone with which the individual is infected to cause disease—the clone's “virulence.” Public-health officials and infectious disease experts would like to know the geographic distribution of the virulent S. aureus clones that cause invasive infections, because this information should help them understand how these pathogens spread and thus how to control them. Different clones of S. aureus can be distinguished by “molecular typing,” the determination of clone-specific sequences of nucleotides in variable regions of the bacterial genome (the bacterium's blueprint; genomes consist of DNA, long chains of nucleotides). In this study, the researchers use molecular typing to map the geographic distribution of MRSA and methicillin-sensitive S. aureus (MSSA) clones causing invasive infections in Europe; a MRSA clone emerges when an MSSA clone acquires antibiotic resistance from another type of bacteria so it is useful to understand the geographic distribution of both MRSA and MSSA.
What Did the Researchers Do and Find?
Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 European countries collected almost 3,000 MRSA and MSSA isolates from patients with invasive S. aureus infections. The isolates were sent to the relevant national staphylococcal reference laboratory (SRL) where they were characterized by quality-controlled sequence typing of the variable region of a staphylococcal gene called spa (spa typing). The spa typing data were entered into a central database and then analyzed by a public, purpose-built Web-based mapping tool (SRL-Maps), which provides interactive access and easy-to-understand illustrations of the geographical distribution of S. aureus clones. Using this mapping tool, the researchers found that there was a wide geographical distribution of spa types across Europe with some types being common in all European countries. MSSA isolates were more diverse than MRSA isolates and the genetic diversity (variability) of MRSA differed considerably between countries. Most importantly, major MRSA spa types occurred in distinct geographical clusters.
What Do These Findings Mean?
These findings provide the first representative snapshot of the genetic population structure of S. aureus across Europe. Because the researchers used spa typing, which analyzes only a small region of one gene, and characterized only 3,000 isolates, analysis of other parts of the S. aureus genome in more isolates is now needed to build a complete portrait of the geographical abundance of the S. aureus clones that cause invasive infections in Europe. However, the finding that MRSA spa types occur mainly in geographical clusters has important implications for the control of MRSA, because it indicates that a limited number of clones are spreading within health care networks, which means that MRSA is mainly spread by patients who are repeatedly admitted to different hospitals. Control efforts aimed at interrupting this spread within and between health care institutions may be feasible and ultimately successful, suggest the researchers, and should be strongly encouraged. In addition, this study shows how, by sharing typing results on a Web-based platform, an international surveillance network can provide clinicians and infection control teams with crucial information about the dynamics of pathogens such as S. aureus, including early warnings about emerging virulent clones.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Franklin D. Lowy
The UK Health Protection Agency provides information about Staphylococcus aureus
The UK National Health Service Choices Web site has pages on staphylococcal infections and on MRSA
The US National Institute of Allergy and Infectious Disease has information about MRSA
The US Centers for Disease Control and Infection provides information about MRSA for the public and professionals
MedlinePlus provides links to further resources on staphylococcal infections and on MRSA (in English and Spanish)
SRL-Maps can be freely accessed
PMCID: PMC2796391  PMID: 20084094
8.  Outcome of Debridement and Retention in Prosthetic Joint Infections by Methicillin-Resistant Staphylococci, with Special Reference to Rifampin and Fusidic Acid Combination Therapy 
The management of prosthetic joint infections remains a clinical challenge, particularly infections due to methicillin-resistant staphylococci. Previously, this infection was considered a contraindication to debridement and retention strategies. This retrospective cohort study examined the treatment and outcomes of patients with arthroplasty infection by methicillin-resistant staphylococci managed by debridement and retention in conjunction with rifampin-fusidic acid combination therapy. Over an 11-year period, there were 43 patients with infection by methicillin-resistant staphylococci managed with debridement and retention. This consisted of close-interval repeated arthrotomies with pulsatile lavage. Rifampin was combined with fusidic acid for the majority of patients (88%). Patients were monitored for a median of 33.5 months (interquartile range, 20 to 54 months). Overall, 9 patients experienced treatment failure, with 12- and 24-month estimates of infection-free survival of 86% (95% confidence interval [CI], 71 to 93%) and 77% (95% CI, 60 to 87%), respectively. The following factors were associated with treatment failure: methicillin-resistant Staphylococcus aureus (MRSA) arthroplasty infection, a single surgical debridement or ≥4 debridements, and the receipt of less than 90 days of antibiotic therapy. Patients with infection by methicillin-resistant coagulase-negative staphylococci (MR-CNS) were less likely to fail treatment. The overall treatment success rate reported in this study is comparable to those of other treatment modalities for prosthetic joint infections by methicillin-resistant staphylococci. Therefore, the debridement and retention of the prosthesis and rifampin-based antibiotic therapy are a valid treatment option for carefully selected patients.
PMCID: PMC3535910  PMID: 23114758
9.  Prosthetic joint infection due to Salmonella species: a case series 
BMC Infectious Diseases  2014;14(1):633.
Prosthetic joint infection (PJI) due to Salmonella is rare. Numerous outbreaks of Salmonella have been reported throughout the United States in the last decade. We reviewed and analyzed cases of Salmonella PJI seen at our institution.
The medical records of all patients diagnosed with a Salmonella PJI between 1969–2013 were reviewed. Patients were followed till death, treatment failure or loss to follow-up.
Six patients of Salmonella PJI were identified during the 44 year study period. Five were male; median age was 63.5 years (range 52–76). Five patients were immunodeficient. Five had a total hip arthroplasty infection, while one had a total knee arthroplasty infection. Median prosthesis age at the time of diagnosis of first episode of Salmonella PJI was 5 years (range 4 months-9 years). Four presented with fever and constitutional signs within two weeks of symptom onset. Two patients each had gastrointestinal symptoms and Salmonella bacteremia. Salmonella enterica serovar Enteritidis was the most common organism isolated (4 patients). None were Salmonella enterica serovar Typhi. Initial management included aspiration and antimicrobial therapy only (3), debridement and component retention (1) and two-staged exchange (2). All four patients treated without resection failed treatment a median of 2.5 months (range 2–11) after diagnosis and required resection arthroplasty. All six patients who underwent prosthesis removal (and exchange or arthrodesis) had successful outcome with a median duration of follow-up of 11 years (range 4–21). Three of these received oral antimicrobial therapy for a median duration eight weeks (range 4–8) and three received parenteral antimicrobial therapy for a median duration of six weeks (range 4–6).
The increase in Salmonella outbreaks does not seem to lead to increased Salmonella PJI. PJIs due to Salmonella remain rare, and the presentation is often acute with fever. It frequently occurs in immunocompromised patients. In our patient population, removal of prosthesis with or without reimplantation, along with 4–6 weeks of effective parenteral antimicrobial therapy was most often associated with successful eradication of infection.
PMCID: PMC4258011  PMID: 25424009
Salmonella; Prosthetic joint infections; Arthroplasty
10.  Laboratory and Clinical Characteristics of Staphylococcus lugdunensis Prosthetic Joint Infections▿  
Journal of Clinical Microbiology  2010;48(5):1600-1603.
Staphylococcus lugdunensis is a coagulase-negative staphylococcus that has several similarities to Staphylococcus aureus. S. lugdunensis is increasingly being recognized as a cause of prosthetic joint infection (PJI). The goal of the present retrospective cohort study was to determine the laboratory and clinical characteristics of S. lugdunensis PJIs seen at the Mayo Clinic in Rochester, MN, between 1 January 1998 and 31 December 2007. Kaplan-Meier survival methods and Wilcoxon sum-rank analysis were used to determine the cumulative incidence of treatment success and assess subset comparisons. There were 28 episodes of S. lugdunensis PJIs in 22 patients; half of those patients were females. Twenty-five episodes (89%) involved the prosthetic knee, while 3 (11%) involved the hip. Nine patients (32%) had an underlying urogenital abnormality. Among the 28 isolates in this study tested by agar dilution, 24 of 28 (86%) were oxacillin susceptible. Twenty of the 21 tested isolates (95%) lacked mecA, and 6 (27%) of the 22 isolates tested produced β-lactamase. The median durations of parenteral β-lactam therapy and vancomycin therapy were 38 days (range, 23 to 42 days) and 39 days (range, 12 to 60 days), respectively. The cumulative incidences of freedom from treatment failure (standard deviations) at 2 years were 92% (±7%) and 76% (±12%) for episodes treated with a parenteral β-lactam and vancomycin, respectively (P = 0.015). S. lugdunensis is increasingly being recognized as a cause of PJIs. The majority of the isolates lacked mecA. Episodes treated with a parenteral β-lactam antibiotic appear to have a more favorable outcome than those treated with parenteral vancomycin.
PMCID: PMC2863876  PMID: 20181900
11.  Prosthetic Joint Infection in Patients with Rheumatoid Arthritis: An Outcome Analysis Compared with Controls 
PLoS ONE  2013;8(8):e71666.
Patients with rheumatoid arthritis (RA) have been shown to have an increased susceptibility to the development of prosthetic joint infection (PJI) after hip or knee replacement. However, little information is available on the demographic data, outcome of treatment and prognostic factors in RA patients when compared to those in non-RA patients.
Methods/Principal Findings
We performed a retrospective cohort analysis of all cases of PJI that were treated at our institution between 2002 and 2008. Of 346 episodes of PJI during the study period, 46 (13.3%) occurred in patients with RA. Compared to the non-RA cohort, RA patients with PJI were female predominant (74% vs 27%, p<0.001), younger (median age, 51 vs 63 years, p<0.001) and developed infection earlier (median joint age, 72 vs 128 days, p<0.001). The 2-year survival rate free of treatment failure was lower in RA patients with PJI episodes either treated with débridement (22% vs 52%, p = 0.002) or two-stage exchange (78% vs 95%, p = 0.004). A longer duration of symptoms before débridement surgery (median, 11 vs 5 days, p = 0.015), and absence of antibiotics in bone cement for two-stage exchange (relative risk, 8.0; p = 0.02) were associated with treatment failure in patients with RA.
The outcome of PJI in RA patients was generally worse than that in non-RA patients. Risk of treatment failure increased in the setting of delayed débridement and two-stage exchange without the use of antibiotic-impregnated bone cement. These findings highlight the importance of vigilant monitoring and aggressive treatment for PJI in RA patients.
PMCID: PMC3753295  PMID: 23990969
12.  Outcome of Acute Prosthetic Joint Infections Due to Gram-Negative Bacilli Treated with Open Debridement and Retention of the Prosthesis▿  
Antimicrobial Agents and Chemotherapy  2009;53(11):4772-4777.
The aim of our study was to evaluate the outcome of acute prosthetic joint infections (PJIs) due to gram-negative bacilli (GNB) treated without implant removal. Patients with an acute PJI due to GNB diagnosed from 2000 to 2007 were prospectively registered. Demographics, comorbidity, type of implant, microbiology data, surgical treatment, antimicrobial therapy, and outcome were recorded. Classification and regression tree analysis, the Kaplan-Meier survival method, and the Cox regression model were applied. Forty-seven patients were included. The mean age was 70.7 years, and there were 15 hip prostheses and 32 knee prostheses. The median number of days from the time of arthroplasty was 20. The most frequent pathogens were members of the Enterobacteriaceae family in 41 cases and Pseudomonas spp. in 20 cases. Among the Enterobacteriaceae, 14 were resistant to ciprofloxacin, while all Pseudomonas aeruginosa isolates were susceptible to ciprofloxacin. The median durations of intravenous and oral antibiotic treatment were 14 and 64 days, respectively. A total of 35 (74.5%) patients were in remission after a median follow-up of 463 days (interquartile range, 344 to 704) days. By use of the Kaplan-Meier survival curve, a C-reactive protein (CRP) concentration of ≤15 mg/dl (P = 0.03) and receipt of a fluoroquinolone, when all GNB isolated were susceptible (P = 0.0009), were associated with a better outcome. By use of a Cox regression model, a CRP concentration of ≤15 mg/dl (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.05 to 12.5; P = 0.043) and receipt of a fluoroquinolone (OR, 9.09; 95% CI, 1.96 to 50; P = 0.005) were independently associated with better outcomes. Open debridement without removal of the implant had a success rate of 74.5%, and the factors associated with good prognosis were a CRP concentration at the time of diagnosis ≤15 mg/dl and treatment with a fluoroquinolone.
PMCID: PMC2772308  PMID: 19687237
13.  Early prosthetic joint infections treated with debridement and implant retention 
Acta Orthopaedica  2012;83(3):227-232.
Background and purpose
Debridement and retention of the prosthesis is often attempted to treat early prosthetic joint infection (PJI). However, previous studies have found inconsistent results, with success rates ranging from 21% to 100%, and little has been written in the literature about hip function. We have therefore analyzed the clinical and functional outcome of early PJIs treated with this procedure.
Patients and methods
38 patients with early PJI after primary hip arthroplasty who were treated with debridement and retention of the implant between 1998 and 2005 were studied prospectively, with a median follow-up time of 4 (0.8–10) years. Early infection was defined as that which occurred within 4 weeks of index arthroplasty. The primary outcome measure was infection control. Functional outcome was assessed with the Harris hip score.
27 of 38 patients were successfully treated, with no signs of infection or continued antibiotic treatment at the latest follow-up. Median Harris hip score was 86 (47–100) points. In 9 of the 11 patients for whom treatment failed, infection was successfully treated with 1-stage or 2-stage reimplantation or resection. Intraoperative cultures were positive in 36 hips, and the most frequently isolated organisms were Staphylococcus aureus and coagulase-negative staphylococci (CoNS). 15 infections were polymicrobial, and only 8 of them were successfully treated with debridement and retention of the implant.
Our data suggest that debridement and retention of the prosthesis is a reasonable treatment option in early PJI after primary hip arthroplasty, with satisfactory functional results.
PMCID: PMC3369146  PMID: 22489892
14.  Efficacy of Daptomycin in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus 
Methicillin-resistant Staphylococcus aureus is becoming increasingly prevalent as both a nosocomial and a community-acquired pathogen. Daptomycin, a lipopeptide antibiotic now in phase III clinical trials, is rapidly bactericidal in vitro against a range of gram-positive organisms, including methicillin-resistant S. aureus (MRSA). In this study, we compared the efficacy of daptomycin with that of vancomycin, each with or without rifampin, in a model of experimental aortic valve endocarditis due to MRSA. The infecting strain (MRSA strain 32) was susceptible to daptomycin (MIC = 1 μg/ml), vancomycin (MIC = 0.5 μg/ml), and rifampin (MIC = 0.5 μg/ml). Daptomycin was administered at 25 or 40 mg/kg q24h (q24h) by subcutaneous injection in an attempt to simulate human doses of 4 and 6 mg/kg q24h, respectively. Vancomycin was given at 150 mg/kg q24h by continuous intravenous infusion. Rifampin was given at 25 mg/kg by intramuscular injection q24h. Treatment was started 6 h postinoculation and continued for 4.5 days. Outcome was assessed by counting the residual viable bacteria in vegetations. The mean peak daptomycin levels in serum at 2 h after subcutaneous administration of 25 and 40 mg/kg were 64 and 91 μg/ml, respectively. Daptomycin was undetectable in serum at 24 h. The total exposure was comparable to that achieved clinically in humans receiving the drug. Bacterial counts (mean log10 number of CFU per gram ± the standard deviation) in untreated controls reached 10.6 ± 0.8. In treated rats, bacterial counts were as follows: vancomycin, 7.1 ± 2.5; daptomycin at 25 mg/kg, 5.5 ± 1.7; daptomycin at 40 mg/kg, 4.2 ± 1.5. The difference between daptomycin at 40 mg/kg and vancomycin at 150 mg/kg was statistically significant (P = 0.004). In the study of combination therapy, vegetation bacterial counts were as follows: daptomycin at 40 mg/kg, 4.6 ± 1.6; rifampin, 3.6 ± 1.3; vancomycin plus rifampin, 3.3 ± 1.1; daptomycin plus rifampin, 2.9 ± 0.8. The difference between daptomycin and daptomycin plus rifampin was statistically significant (P = 0.006). These results support the continued evaluation of daptomycin for serious MRSA infections, including infective endocarditis.
PMCID: PMC153308  PMID: 12709345
15.  Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization: prevention of antimicrobial resistance and effect of host factors on outcome. 
Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim-sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83%] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing both pressure and other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds. There were no significant differences in toxicity between the two regimens. Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state. The response to either combination depended on host factors, particularly age and the site of MRSA colonization.
PMCID: PMC187962  PMID: 8328783
16.  Current management of prosthetic joint infections in adults: results of an Emerging Infections Network survey 
There is a dearth of guidance on the management of prosthetic joint infections (PJIs), in particular because of the lack of high-quality evidence for optimal antibiotics. Thus, we designed a nine-question survey of current practices and preferences among members of the Emerging Infections Network, a CDC-sponsored network of infectious diseases physicians, which was distributed in May 2012. In total, 556 (47.2%) of 1178 network members responded. As first-line antibiotic choice for MSSA PJI, 59% of responders indicated oxacillin/nafcillin, 33% cefazolin and 7% ceftriaxone; the commonest alternative was cefazolin (46%). For MRSA PJI, 90% preferred vancomycin, 7% daptomycin and 0.8% ceftaroline; the commonest alternative was daptomycin (65%). Antibiotic selection for coagulase-negative staphylococci varied depending on meticillin susceptibility. For staphylococcal PJIs with retained hardware, most providers would add rifampicin. Propionibacterium is usually treated with vancomycin (40%), penicillin (23%) or ceftriaxone (17%). Most responders thought 10–19% of all PJIs were culture-negative. Culture-negative PJIs of the lower extremities are usually treated with a vancomycin/fluoroquinolone combination, and culture-negative shoulder PJIs with vancomycin/ceftriaxone. The most cited criteria for selecting antibiotics were ease of administration and the safety profile. A treatment duration of 6–8 weeks is preferred (by 77% of responders) and is mostly guided by clinical response and inflammatory markers. Ninety-nine percent of responders recommend oral antibiotic suppression (for varying durations) in patients with retained hardware. In conclusion, there is considerable variation in treatment of PJIs both with identified pathogens and those with negative cultures. Future studies should aim to identify optimum treatment strategies.
PMCID: PMC3572796  PMID: 23312602
Prosthetic joint infection; Osteomyelitis; Staphylococcus aureus; Antibiotic; Treatment
17.  2-stage revision recommended for treatment of fungal hip and knee prosthetic joint infections 
Acta Orthopaedica  2013;84(6):517-523.
Background and purpose
Fungal prosthetic joint infections are rare and difficult to treat. This systematic review was conducted to determine outcome and to give treatment recommendations.
Patients and methods
After an extensive search of the literature, 164 patients treated for fungal hip or knee prosthetic joint infection (PJI) were reviewed. This included 8 patients from our own institutions.
Most patients presented with pain (78%) and swelling (65%). In 68% of the patients, 1 or more risk factors for fungal PJI were found. In 51% of the patients, radiographs showed signs of loosening of the arthroplasty. Candida species were cultured from most patients (88%). In 21% of all patients, fungal culture results were first considered to be contamination. There was co-infection with bacteria in 33% of the patients. For outcome analysis, 119 patients had an adequate follow-up of at least 2 years. Staged revision was the treatment performed most often, with the highest success rate (85%).
Fungal PJI resembles chronic bacterial PJI. For diagnosis, multiple samples and prolonged culturing are essential. Fungal species should be considered to be pathogens. Co-infection with bacteria should be treated with additional antibacterial agents.
We found no evidence that 1-stage revision, debridement, antibiotics, irrigation, and retention (DAIR) or antifungal therapy without surgical treatment adequately controls fungal PJI. Thus, staged revision should be the standard treatment for fungal PJI. After resection of the prosthesis, we recommend systemic antifungal treatment for at least 6 weeks—and until there are no clinical signs of infection and blood infection markers have normalized. Then reimplantation can be performed.
PMCID: PMC3851663  PMID: 24171675
18.  Remission after treatment of osteoarticular infections due to Pseudomonas aeruginosa versus Staphylococcus aureus: a case-controlled study 
International Orthopaedics  2011;36(5):1065-1071.
Osteoarticular infections due to methicillin-susceptible Staphylococcus aureus (MSSA) or its methicillin-resistant variant (MRSA) are feared due to treatment failures. According to clinical experience, Pseudomonas aeruginosa may reveal less long-term remission than S. aureus.
A case-controlled study comparing outcomes of osteoarticular infections due to P. aeruginosa vs S. aureus was performed at Geneva University Hospitals.
A total of 111 S. aureus (including 37 MRSA) and 20 P. aeruginosa osteoarticular infections were analysed in 131 patients: arthroplasties (n = 38), fracture fixation devices (n = 56), native joint arthritis (n = 7) and osteomyelitis without implant (n = 30). The median active follow-up time was 4 years. The patients underwent a median number of two surgical interventions for P. aeruginosa infections compared to two for S. aureus (two for MRSA), while the median duration of antibiotic treatment was 87 days for P. aeruginosa and 46 days for S. aureus infections (58 days for MRSA) (all p > 0.05). Overall, Pseudomonas-infected patients tended towards a lower remission rate than those infected with S. aureus (12/20 vs 88/111; p = 0.06). This was similar when P. aeruginosa was compared with MRSA alone (12/20 vs 30/37; p = 0.08). In multivariate logistic regression analyses adjusting for case mix, odds ratios (OR) for remission were as follows: P. aeruginosa vs S. aureus [OR 0.4, 95% confidence interval (CI) 0.1–1.2], number of surgical interventions (OR 0.6, 95% CI 0.5–1.0) and duration of antibiotic treatment (OR 1.0, 95% CI 1.0–1.0).
Despite a similar number of surgical interventions and longer antibiotic treatment, osteoarticular infections due to P. aeruginosa tended towards a lower remission rate than infections due to S. aureus in general or MRSA in particular.
PMCID: PMC3337090  PMID: 21983903
Medicine & Public Health; Orthopedics
19.  Treatment of acute periprosthetic infections with prosthesis retention: Review of current concepts 
World Journal of Orthopedics  2014;5(5):667-676.
Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty, occurring in approximately 1%-2% of all cases. With growing populations and increasing age, PJI will have a growing effect on health care costs. Many risk factors have been identified that increase the risk of developing PJI, including obesity, immune system deficiencies, malignancy, previous surgery of the same joint and longer operating time. Acute PJI occurs either postoperatively (4 wk to 3 mo after initial arthroplasty, depending on the classification system), or via hematogenous spreading after a period in which the prosthesis had functioned properly. Diagnosis and the choice of treatment are the cornerstones to success. Although different definitions for PJI have been used in the past, most are more or less similar and include the presence of a sinus tract, blood infection values, synovial white blood cell count, signs of infection on histopathological analysis and one or more positive culture results. Debridement, antibiotics and implant retention (DAIR) is the primary treatment for acute PJI, and should be performed as soon as possible after the development of symptoms. Success rates differ, but most studies report success rates of around 60%-80%. Whether single or multiple debridement procedures are more successful remains unclear. The use of local antibiotics in addition to the administration of systemic antibiotic agents is also subject to debate, and its pro’s and con’s should be carefully considered. Systemic treatment, based on culture results, is of importance for all PJI treatments. Additionally, rifampin should be given in Staphylococcal PJIs, unless all foreign material is removed. The most important factors contributing to treatment failure are longer duration of symptoms, a longer time after initial arthroplasty, the need for more debridement procedures, the retention of exchangeable components, and PJI caused by Staphylococcus (aureus or coagulase negative). If DAIR treatment is unsuccessful, the following treatment option should be based on the patient health status and his or her expectations. For the best functional outcome, one- or two-stage revision should be performed after DAIR failure. In conclusion, DAIR is the obvious choice for treatment of acute PJI, with good success rates in selected patients.
PMCID: PMC4133475  PMID: 25405096
Arthroplasty; Prosthesis; Infection; Periprosthetic joint infection; Retention; Debridement antibiotics and implant retention; Debridement; Acute
20.  Efficacy of Usual and High Doses of Daptomycin in Combination with Rifampin versus Alternative Therapies in Experimental Foreign-Body Infection by Methicillin-Resistant Staphylococcus aureus ▿ †  
Antimicrobial Agents and Chemotherapy  2010;54(12):5251-5256.
The treatment of prosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to be a challenge for the clinician. The aim of this study was to evaluate the efficacies of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg of body weight/day, respectively, in humans) and in combination with rifampin and to compare the activities to those of conventional anti-MRSA therapies. We used MRSA strain HUSA 304, with the following MICs and minimal bactericidal concentrations (MBCs), respectively: daptomycin, 1 μg/ml and 4 μg/ml; vancomycin, 2 μg/ml and 4 μg/ml; linezolid, 2 μg/ml and >32 μg/ml; and rifampin, 0.03 μg/ml and 0.5 μg/ml. In time-kill curves, only daptomycin and its combinations with rifampin achieved a bactericidal effect in log and stationary phases. For in vivo studies, we used a rat foreign-body infection model. Therapy was administered for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin at 25 mg/kg/12 h, and linezolid at 35 mg/kg/12 h, and each antibiotic was also combined with rifampin. Among monotherapies, daptomycin at 100 mg/kg/day and rifampin performed better than vancomycin and linezolid. In combination with rifampin, both dosages of daptomycin were significantly better than all other combinations, but daptomycin at 100 mg/kg/day plus rifampin achieved better cure rates at day 11 (P < 0.05) than daptomycin at 45 mg/kg/day plus rifampin. Resistant strains were found in monotherapies with rifampin and daptomycin at 45 mg/kg/day. In conclusion, daptomycin at high doses was the most effective monotherapy and also improved the efficacy of the combination with rifampin against foreign-body infections by MRSA. Clinical studies should confirm whether this combination may be considered the first-line treatment for foreign-body infections by MRSA in humans.
PMCID: PMC2981248  PMID: 20921321
21.  Polymicrobial Prosthetic Joint Infections: Risk Factors and Outcome 
Limited data are available regarding the risk factors and outcome of polymicrobial prosthetic joint infection (PJIs) when compared with monomicrobial PJI. Between January 1998 and November 2006, we retrospectively identified 34 of 174 prosthetic joint infections (19%) were polymicrobial. The 2-year cumulative probability of success of treating polymicrobial and monomicrobial PJIs was 63.8% and 72.8%, respectively. Twenty-six percent, 38%, and 29% of PJIs were treated with two-stage exchange, débridement and retention, or resection arthroplasty, respectively, and the 2-year survival rate free of treatment failure in each group was 77.7% (95% confidence interval, 42.8%–94.2%), 52.7% (95% confidence interval, 28.4%–75.9%), and 64.2% (95% confidence interval, 28.7%–88.9%). Methicillin-resistant Staphylococcus aureus (26.4% versus 7.1%) and anaerobes (11.7% versus 2.8%) were more common in polymicrobial PJIs. Polymicrobial PJIs occurred in patients with a soft tissue defect/dehiscence (23.5% versus 2.8%), drainage (79.4% versus 39.2%), or prior local irradiation (8.8% versus 0.71%). We found the following factors associated with polymicrobial prosthetic joint infections: the presence of a soft tissue defect/wound dehiscence (odds ratio, 5.9), drainage (odds ratio, 5.0), and age 65 years or older (odds ratio, 2.8).
Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2384015  PMID: 18421538
22.  Epidemiology and Outcomes of Community-Associated Methicillin-Resistant Staphylococcus aureus Infection▿  
Journal of Clinical Microbiology  2007;45(6):1705-1711.
Over a 2-year period (2003 to 2005) patients with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-susceptible Staphylococcus aureus (CA-MSSA) infections were prospectively identified. Patients infected with CA-MRSA (n = 102 patients) and CA-MSSA (n = 102 patients) had median ages of 46 and 53 years, respectively; the most common sites of infection in the two groups were skin/soft tissue (80 and 93%, respectively), respiratory tract (13 and 6%, respectively), and blood (4 and 1%, respectively). Fourteen percent of patients with CA-MRSA infections and 3% of patients with CA-MSSA infections had household contacts with similar infections (P < 0.01). Among the CA-MRSA isolates, the pulsed-field gel electrophoresis (PFGE) groups detected were USA300 (49%) and USA100 (13%), with 27 PFGE groups overall; 71% of the isolates were staphylococcal chromosome cassette mec (SCCmec) type IV, 29% were SCCmec type II, and 54% had the Panton-Valentine leucocidin (PVL) gene. Among the CA-MSSA isolates there were 33 PFGE groups, with isolates of the USA200 group comprising 11%, isolates of the USA600 group comprising 11%, isolates of the USA100 group comprising 10%, and isolates of the PVL type comprising 10%. Forty-six and 18% of the patients infected with CA-MRSA and CA-MSSA, respectively, were hospitalized (P < 0.001). Fifty percent of the patients received antibiotic therapy alone, 5% received surgery alone, 30% received antibiotics and surgery, 3% received other therapy, and 12% received no treatment. The median durations of antibiotic therapy were 12 and 10 days in the CA-MRSA- and CA-MSSA-infected patients, respectively; 48 and 56% of the patients in the two groups received adequate antimicrobial therapy, respectively (P < 0.001). The clinical success rates of the initial therapy in the two groups were 61 and 84%, respectively (P < 0.001); recurrences were more common in the CA-MRSA group (recurrences were detected in 18 and 6% of the patients in the two groups, respectively [P < 0.001]). CA-MRSA was an independent predictor of clinical failure in multivariate analysis (odds ratio, 3.4; 95% confidence interval, 1.7 to 6.9). In the community setting, the molecular characteristics of the S. aureus strains were heterogeneous. CA-MRSA infections were associated with a more adverse impact on outcome than CA-MSSA infections.
PMCID: PMC1933099  PMID: 17392441
23.  Periprosthetic Infection Due to Resistant Staphylococci: Serious Problems on the Horizon 
Prosthetic joint infections (PJI) caused by methicillin-resistant staphylococci represent a major therapeutic challenge. We examined the effectiveness of surgical treatment in treating infection of total hip or knee arthroplasty caused by methicillin-resistant staphylococcal strains and the variables influencing treatment success. One hundred and twenty-seven patients were treated at our institution between 1999 and 2006. There were 58 men and 69 women, with an average age of 66 years. Patients were followed for a minimum of 2 years or until recurrence of infection. Débridement and retention of the prosthesis was performed in 35 patients and resection arthroplasty in 92. Débridement controlled the infection in only 37% of cases whereas two-stage exchange arthroplasty controlled the infection in 75% of hips and 60% of knees. Preexisting cardiac disease was associated with a higher likelihood of failure to control infection in all treatment groups. Antibiotic-resistant Staphylococci continue to compromise treatment outcome of prosthetic joint infections, especially in patients with medical comorbidities. New preventive and therapeutic strategies are needed.
Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2690767  PMID: 19408061
24.  Two-stage hip revision arthroplasty with a hexagonal modular cementless stem in cases of periprosthetic infection 
Two-stage revision arthroplasty is today regarded as the gold standard treatment method for deep prosthetic joint infection. The aim of the present study was to evaluate clinical and functional outcomes with the Modular Universal Tumor And Revision System (MUTARS) RS stem in patients undergoing two-stage revisions.
The functional and clinical outcomes for 43 patients who had undergone two-stage revision procedures for PJI were analyzed in a retrospective study. The minimum follow-up period was 24 months. Shorter follow-up periods were only observed when there were complications such as loosening or recurrent infection. The mean follow-up period was 3.86 years (range 7 months to 11.6 years).
The success rate with infection control for PJI was 93%. Reinfection occurred in four cases (7%). The risk of reinfection after MRSA infection was 20.5 times greater (P >0.01) than with sensitive or unknown bacteria. Two aseptic loosening occurred after 7 and 20 months. The average Harris Hip Score was 80 (range 62–93).
This retrospective study showed a 93% rate of eradication using specific antibiotic therapy. With the modular MUTARS RS stem, there was a low rate of aseptic loosening of 4.6%. MRSA infection was identified as a risk factor for reinfection. The two-stage procedure with modular cementless implants used is therefore appropriate for treating periprosthetic infections associated with hip endoprostheses.
PMCID: PMC4289174  PMID: 25428415
Two-stage revision; Periprosthetic infection; Hip arthroplasty; Cementless; Modular; Hexagonal
25.  Antibacterial Susceptibility Patterns and Cross-Resistance of Methicillin Resistant and Sensitive Staphyloccus Aureus Isolated from the Hospitalized Patients in Shiraz, Iran 
Brazilian Journal of Microbiology  2010;41(3):567-573.
Nosocomial infections caused by methicillin-resistant staphylococci (MRSA) pose a serious problem in many countries. This study aimed to determine the antibacterial susceptibility patterns of methicillin sensitive and resistant Staphylococcus aureus isolates from the hospitalized patients. Totally 356 isolates of Staphylococcus aureus (S. aureus) including 200, 137 and 19 corresponding to MSSA, MRSA, and intermediate MRSA strains, respectively were isolated. Antibacterial susceptibility patterns of the isolates to 14 antibiotics were examined using Kirby-Bauer method. MICs of 15 antibiotics to 156 MRSA isolates were determined by E test method. Cross-resistances of MRSA isolates (137+19) to the other tested antibiotics were also determined. S.aureus with high frequencies were isolated from the blood, sputum and deep wound samples. All of 200 MSSA isolates were sensitive to oxacillin, vancomycin, tecoplanin, rifampin, linezolid, quinupristin/dalfopristin, mupirocin and fusidic acid. A gradient of reduced susceptibility of MSSA to cephalexin, co-trimoxazole, ciprofloxacin, clindamycin, tetracycline, erythromycin and gentamicin were evident. MRSA isolates were sensitive to vancomycin, tecoplanin, linezolid, quinupristin/dalfopristin, mupirocin and fusidic acid, while reduced susceptibility of them to rifampin, co-trimoxazole, clindamycin, cephalexin, tetracycline, ciprofloxacin, erythromycin and gentamicin were observed. MRSA isolates exhibited a high range of cross-resistance to the eight tested antibiotics. Overall, co-trimoxazole, ciprofloxacin, clindamycin, tetracycline, erythromycin and gentamicin showed low activity against MSSA and MRSA isolates which may indicate they are not suitable to be used in clinical practices. To preserve the effectiveness of antibiotics, rational prescription and concomitant application of preventive measures against the spread of MRSA are recommended.
PMCID: PMC3768665  PMID: 24031530
MRSA; minimum inhibitory concentration; empirical therapy

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