PIANO study provides insight into successful management of prosthetic joint infections

Prosthetic joint replacement surgery changes the lives of millions of people each year, but complications, including infection of the prosthetic joint, occur in 1-2% of patients after major joint replacement surgery.

Prosthetic joint infections (PPIs) cause patient morbidity and impose a significant financial burden on the healthcare system, with annual costs in the United States exceeding $1.6 billion in 2020. Experts predict that there will be 4 million total knee and hip replacement surgeries per year in the United States by 2030. Determining the best management is critical for optimal outcomes.

There are few randomized controlled trials (RCTs) to guide the best surgical and antimicrobial management, leading to a poor evidence base of the Infectious Diseases Society of America’s 2012 PJI guidelines. Most of the data comes from small retrospective studies conducted in centers specializing in PJI, and registry data often underestimate the true incidence, particularly of late acute PJI. To address this knowledge gap, the Prosthetic Joint Infection in Australia and New Zealand observation (PIANO) study was conducted.

The PIANO study was a prospective observational study of the characteristics, etiology and initial management of PPI from July 2014 to December 2017 in 27 hospitals in Australia and New Zealand. The study included 783 patients with PJI – 427 knees (54.5%), 323 hips (41.3%), 25 shoulders (3.2%), six elbows (0.8%) and two ankles ( 0.3%) joint infections – initially 90-day outcomes, categorized according to PJI definitions, microbiological classification (monomicrobial, polymicrobial, or culture negative), and surgical management strategy.

Surgical strategies included:

• debridement, antibiotics, irrigation, implant retention (DAIR);
• two-stage exchange arthroplasty;
• one-stage exchange arthroplasty;
• suppressive antibiotics alone;
• excision arthroplasty; and
• no plan identified.

PJI’s definitions were:

• Early PJI: 30 days or less after the initial joint replacement operation;
• Late acute PJI (LA-PJI): more than 30 days after implantation, but with a duration of symptoms of 7 days or less without evidence of a sinus tract;
• Indeterminate late PJI: more than 30 days since implantation and duration of symptoms between 8 and 30 days without signs of sinus trajectory; and
• Late chronic PJI: more than 30 days since implantation and duration of symptoms greater than 30 days or presence of a sinus pathway.

LA-PJI was the most common type, accounting for 44.8% of infections, followed by early PJI (25%) and late chronic PJI (18.9%). LA-PJI was more likely to be due to an infected knee prosthesis (71%), while hip infections were more likely to be early PJI (59%), with similar rates of infection chronic in both cases. The most common comorbidities were diabetes (22.1%) and ischemic heart disease (16.8%), with no association between comorbidities and type of PPI.

Most infections were monomicrobial, followed by polymicrobial and culture negative. LA-PJIs were more likely to be monomicrobial (81.2%) than early PJIs (49.5%), with the majority due to Staphylococcus aureus, coagulase-negative staphylococci (CoNS) or beta-hemolytic streptococci. Early infections were polymicrobial 41.3% of the time, with S. aureus and ConS being the most common, and Enterobacteriaceae and Enterococci present in 12.2% and 16.3%, respectively. In chronic infections, 70.3% were monomicrobial and 19.6% were polymicrobial, with CoNS accounting for one-third of organisms, followed by S. aureus, Enterobacteriaceae and Enterococci, each accounting for approximately 5%.

The most used surgical strategy in 66.4% of cases was DAIR, then two-stage revision (18.6%), one-stage revision (4.6%), antibiotic suppression (6.7% ) and excisional arthroplasty (0.9%). DAIR was the main management strategy planned in 70% of LA-PJI, 81.6% of early PJI and 44.6% of chronic PJI, most requiring only a single debridement, often without sheath change , arthroscopic debridement or removal of all infected material.

Empirical antibiotic therapy was started in 82% of cases, vancomycin being the most prescribed (45%), followed by cefazolin (40%), flucloxacillin (32%), piperacillin-tazobactam (9.6% ) and ceftriaxone (6%). The minority of patients received adequate gram-negative coverage in their empiric antibiotic treatment, often due to AmpC organisms.

This 90-day outcome study confirmed that LA-PJI is the most common presentation and demonstrated heterogeneity in the presentation and management of PJI. This was followed by a 24-month outcome analysis of the PIANO cohort to examine relationships between practice variations and offered a platform for constructing interventional studies.

The 653 patients who completed the 24-month follow-up as part of the PIANO cohort were assessed to determine whether treatment success was associated with modifiable variables in surgical and antibiotic management. The primary outcomes defined were clinical cure (alive, no clinical or microbiological evidence of infection and not requiring ongoing antibiotics) and treatment success (clinical cure plus index prosthesis still in place).

Clinical cure was achieved in 69% of patients and 54% had therapeutic success. DAIR was the most common surgical strategy and was most successful in early PJI (74%), with decreasing success in LA-PJI (49%) and chronic PJI (44%). Factors associated with treatment success in univariate analysis were young age, hip as index joint, early infection, higher baseline serum albumin, and absence of chronic kidney disease or malignancy. The success rate was lowest for infections caused by S. aureus (46%), Propionibacterium (Cutibacterium) species (46%) or gram-negative rods (46%), while other organisms had 56% to 58% success and culture negative had 71% success. The PIANO cohort had very few MRSA infections – just 23 – but the success rate was lower with these infections, at 39%.

LA-PJIs were less likely to be successful than early PJIs, but those managed with two-stage revision had similar success as early PJIs (72% versus 79%). LA-PJIs managed with DAIR were only successful in 48% of cases. Treatment success was no different among those treated with rifampin compared to no rifampin (OR 1.15; 95% CI, 0.82-1.61), and this insignificance continued , even when restricted to Gram positive or S. aureus infections only.

Rifampicin was used in 255 episodes, of which 26% suffered an adverse event. There needs to be a large RCT to determine if there is a benefit of adding rifampin in the management of PPI.

Treatment success was determined by non-modifiable variables, including index joint, early or late PPI, causative organism, patient age, and absence of certain comorbidities, but surgical factors and antibiotics (modifiable) were not associated with success. The low success rates with DAIR suggest that revision arthroplasty (one- or two-stage) may be the preferable management strategy in those with LA-PJI, and DAIR for early PJI.

Empirical antibiotic therapy in PPI should target the most likely germs while avoiding too broad-spectrum activity. Unnecessarily broad antibiotic therapy can lead to the development of antibiotic resistance and increase the risk of adverse events.

The PIANO cohort showed that early PJIs were more likely to be polymicrobial than LA-PJIs. The proportion of patients based on type of PJI was analyzed to determine empirical treatment regimens that will adequately cover the identified organism in 80% of patients without sepsis and 90% with sepsis. Based on these data, the authors proposed empirical treatment based on the type of PJI and signs of sepsis (table).

A similar study conducted in New Zealand evaluating 15 years of microbiological data on PJI of the knee concluded with similar empirical antibiotic treatment recommendations for PJI. The recommendation should increase adequate empirical Gram-negative coverage from the 26% noted in the PIANO cohort. Cefazolin alone is recommended for LA-PJI, often a Gram-positive monomicrobial infection, which is reasonable for Australia and New Zealand because the rate of MRSA was low in these cohorts, but may need to be switched to vancomycin monotherapy in areas with high levels of MRSA.

conclusion

Data from this large cohort showed that the success of PJI treatment is primarily influenced by non-modifiable risk factors compared to surgical and antibiotic strategies, although the timing of PJI from initial arthroplasty should be considered. in the initial surgical management and the empirical selection of antibiotic therapy.

• For more information:
• Kelly M. Percival, PharmD, BCPS AQ-ID, is an Infectious Disease Clinical Pharmacy Specialist at the University of Iowa Hospitals and Clinics. Percival can be contacted at [email protected].