Polymicrobial Foot Infection Patterns Are Common and Associated With Treatment Failure.

Background: That foot infections are predominately polymicrobial has long been recognized, but it is not clear if the various species co-occur randomly or in patterns. We sought nonrandom species co-occurrence patterns that might help better predict prognosis or guide antimicrobial selection. Methods: We analyzed tissue (bone, skin, and other soft tissue), fluid, and swab specimens collected from initial foot infection episodes during a 10-year period using a hospital registry. Nonrandom co-occurrence of microbial species was identified using simple pairwise co-occurrence rates adjusted for multiple comparisons, Markov and conditional random fields, and factor analysis. A historical cohort was used to validate pattern occurrence and identify clinical significance. Results: In total, 156 unique species were identified among the 727 specimens obtained from initial foot infection episodes in 694 patients. Multiple analyses suggested that Staphylococcus aureus is negatively associated with other staphylococci. Another pattern noted was the co-occurrence of alpha-hemolytic Streptococcus, Enterococcus fecalis, Klebsiella, Proteus, Enterobacter, or Escherichia coli, and absence of both Bacteroides and Corynebacterium. Patients in a historical cohort with this latter pattern had significantly higher risk-adjusted rates of treatment failure. Conclusions: Several nonrandom microbial co-occurrence patterns are frequently seen in foot infection specimens. One particular pattern with many Proteobacteria species may denote a higher risk for treatment failure. Staphylococcus aureus rarely co-occurs with other staphylococci.

Discordant isolates in bone specimens from patients with recurrent foot osteomyelitis.

We compared paired operative bone cultures (initial operation and reoperation) for 35 patients who experienced foot osteomyelitis treatment failure at a single hospital. Concordance was poor (kappa = 0.180). Staphylococcus aureus, gram negatives, and anaerobes were the most common discordant bacteria seen at reoperation, while Enterococcus was the most persistent.

Successful Conservative Management of a Large Splenic Abscess Secondary to Infective Endocarditis.

The spleen is the most common abdominal site for systemic septic emboli that often complicate infective endocarditis. Management of an embolic splenic abscess usually involves surgical splenectomy or image-guided drainage, but the natural history of splenic abscess without drainage is unknown. We describe the successful conservative treatment of a large complex splenic abscess with antibiotics alone in a patient with aortic valve infective endocarditis who required an emergent valve replacement surgical procedure. Previous complex abdominal wall operation with the presence of a synthetic mesh made abdominal surgical intervention unfavorable. The splenic abscess resolved completely with no recurrence of infection at the 3-year follow-up.

Methicillin-Resistant Staphylococcus aureus in Foot Osteomyelitis.

BACKGROUND: Conflicting studies exist regarding the impact of methicillin-resistant Staphylococcus aureus (MRSA) on increased time to wound healing, future need for surgical procedures, and likelihood of treatment failure in patients with diabetic foot osteomyelitis. The purpose of this study is to determine the overall significance of MRSA in predicting treatment failure in bone infections of the foot and to determine an appropriate pre-operative and empiric post-operative antibiotic regimen. PATIENTS AND METHODS: Patients presenting with an initial episode of "probable" or "definite" foot osteomyelitis were included for review and analysis if the following criteria were met: (1) Osteomyelitis occurred in the foot (i.e., distal to the malleoli of the ankle); episodes occurring above the ankle were excluded. (2) Patients received either no antibiotics or only oral antibiotics for long-term treatment; episodes managed with long-term parenteral antibiotics were excluded. (3) The infection was managed initially with medical therapy or conservative surgical therapy; episodes managed with major (above-ankle) amputation as the initial treatment were excluded. The primary objective of this study was to assess whether episodes of foot osteomyelitis associated with MRSA resulted in treatment failure more frequently than not. RESULTS: Of 178 episodes included in the study, 50 (28.1%) episodes had treatment failure. Median time-to-treatment failure was 60 days (range 7-598 days). In 28.1% (9/32 episodes) in which treatment failure occurred and 39.0% (41/105) episodes in which no treatment failure occurred, MRSA was present. The presence of MRSA was not significantly associated with treatment failure (p = 0.99). CONCLUSIONS: The presence of MRSA in bone culture and whether antibiotic use had anti-MRSA activity was not associated with increased treatment failure of diabetic foot osteomyelitis in our institution. Empiric antibiotic coverage of MRSA may not be necessary for many patients presenting with foot osteomyelitis.

Treatment Failure and Leg Amputation Among Patients With Foot Osteomyelitis.

We sought to identify factors associated with treatment failure and leg amputations among those patients who presented with foot osteomyelitis. Characteristics, treatments, and outcomes for all patients treated for probable or definite foot osteomyelitis (per consensus definition) between January 2011 and March 2015 were reviewed. Multivariate Cox regression models were used to identify risk factors for treatment failure (unanticipated resection of additional bone or leg amputation) and of leg amputation alone. A total of 184 episodes of foot osteomyelitis met inclusion criteria. Treatment failure occurred in 53 (28.8%) and leg amputation in 21 (11.4%). Risk factors for treatment failure included severe/unaddressed peripheral artery disease, homelessness, Pseudomonas aeruginosa or Escherichia coli bone isolates, serum albumin <2.8 mg/dL, hallux involvement, insulin therapy, 60 or more pack-years smoking, and <7 days of directed antibiotic therapy for a positive bone margin. Delayed primary wound closure (ie, staged operations) had significantly lower treatment failure risk. Unanticipated resection of bone was not associated with leg amputation. Foot osteomyelitis treatment failure is common. Various factors can help identify those at risk for treatment failure and/or leg amputation, and further studies should focused whether initial management or follow-up should change when these factors are present.

Education and Communication in an Interprofessional Antimicrobial Stewardship Program.

CONTEXT: Interprofessional education/interprofessional practice (IPE/IPP) is an essential component in medical education and training. A collaborative interprofessional team environment ensures optimal patient-centered care. OBJECTIVE: To describe the implementation of 2 interprofessional antimicrobial stewardship program (ASP) teams using IPE/IPP and to assess the acceptance rate by the primary medical and surgical teams of ASP recommendations for antimicrobial interventions. METHODS: A business plan for the ASP was approved at 2 academic medical centers used for the present study. During a 3-year study period, 2 interprofessional ASP teams included an attending physician specializing in infectious disease (ID), an ID physician fellow, an ASP pharmacist, physician residents, medical students, pharmacy residents, and pharmacy students. Educational seminars were presented for all adult-admitting physicians to discuss the need for the ASP and the prospective audit and feedback process. Cases were presented for discussion during ASP/ID rounds and recommendations were agreed upon by the ASP team. A motivational interviewing face-to-face technique was frequently used to convey the ASP team recommendation to the primary medical or surgical team in a noncoercive and educational manner. The ASP team recommendations for ASP interventions were documented in the medical records. RESULTS: The overall acceptance rate of recommendations by the primary medical and surgical teams were greater than 90% (2051 of 2266). The most frequent interventions provided were streamline therapy (601), route of administration change (452), bug-drug mismatch (190), and discontinuation of therapy (179). Route of administration change was also the most frequently accepted intervention (96%). CONCLUSIONS: The motivational face-to-face communication technique was particularly useful in conveying ASP team member recommendations to the primary medical or surgical teams. Communicating recommendations as a multidisciplinary team in an educational manner seems to have resulted in to greater acceptance of recommendations.

Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis: a systematic review and meta-analysis.

Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients.

Respiratory syncytial virus lower respiratory tract infection in a pediatric liver transplant recipient treated with oral ribavirin.

The mainstay of therapy for RSV disease is supportive care, although aerosolized ribavirin has been used to treat infants and young children with severe lower respiratory tract infections. Aerosolized ribavirin has adverse effects, high cost and teratogenic potential. We report the case of a pediatric liver transplant recipient diagnosed with lower respiratory RSV infection, who was successfully treated with oral ribavirin.

What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression.

BACKGROUND: Experience with intravenous and aerosolized forms of colistin for the treatment of ventilator-associated pneumonia (VAP) in patients without cystic fibrosis is limited. We aimed to assess the safety and efficacy of colistin for the treatment of VAP. METHODS: We searched MEDLINE and Cochrane Database of Systematic Reviews for studies comparing colistin vs other antibiotics for treatment of VAP in patients without cystic fibrosis. QUOROM guidelines were followed, the I(2) method was used for heterogeneity, and a random-effects model for odds ratio (OR) estimates. RESULTS: Six controlled studies met the inclusion criteria. Clinical response did not differ significantly between colistin and control groups (OR, 1.14; 95% confidence interval [CI], .74-1.77; P = .56; I(2) = 0%). The efficacy of colistin was independent of study design (prospective OR, 0.89 [95% CI, .48-1.66; P = .71; I(2) = 0%]; retrospective OR, 1.45 [95% CI, .79-2.68; P = .23; I(2) = 0%]); randomized trials OR, 0.86 [95% CI, .43-1.74; P = .68; I(2) = 0%]). There was no indication of a significant change in clinical response after controlling for concomitant antibiotic treatment (intercept, 0.121; slope, 0.0315; P = .95). Treatment with colistin vs controls did not affect hospital mortality (OR, 0.92; 95% CI, .50-1.67; P = .78; I(2) = 34.59%) or nephrotoxicity (OR, 1.14; 95% CI, .59-2.20; P = .69; I(2) = 0%). Fourteen single-arm studies have been analyzed, and the results were in concordance with the findings of the controlled studies. CONCLUSIONS: Our results suggest that colistin may be as safe and as efficacious as standard antibiotics for the treatment of VAP.

Pediococcus acidilactici endocarditis successfully treated with daptomycin.

This report describes the first case of persistent bacteremia with endocarditis caused by Pediococcus acidilactici in a 32-year-old male with a history of short gut syndrome following a small bowel transplant. The results showed the utility of sequencing the intergenic spacer region for species identification and successful treatment using daptomycin.

A retrospective study of bacterial infections in cirrhosis.

AIM: To evaluate the incidence of bacterial infections (BI) in hepatic cirrhosis (HC), the pathogen agents involved, to define the risk factors and impact on prognosis. METHODS: There was a retrospective study that enrolled a total of 1046 patients with HC admitted in our clinic between 1.10.2008-31.03.2009 (6 months). Clinical, biological and bacteriological data were monitored. RESULTS: 51 patients (4.9%) were found with BI. In one patient BI was located in three sites: peritoneal, blood and urine, and in 7 patients BI was located in 2 sites. BI location was: peritoneal-26 cases, urinary-20 cases, pneumonia - 8 cases, skin - 4 cases and bacteremia -1 case. 43 episodes were community acquired, while 17 episodes were - nosocomial (peritoneal - 3 cases, lung - 6 cases, skin - 2 cases, urinary - 5 cases). Of the 26 cases with bacterial peritonitis, the etiologic agent was identified in three: E. coli, Klebsiella, Alcaligenes. 18% of patients with HC and BI presented upper GI bleeding. 12 cases required admission to the Intensive Care Unit, where the death rate reached 83%. The risk factors for BI in HC were: decompensated HC OR=58,23 (95% CI 8.63÷1141.31), p-value 10-12, Child Pugh score C: OR =1.99 (95% CI 1.04÷3.8), p-value= 0.02. CONCLUSIONS: In this study the rate of bacterial infections in HC is low compared with the literature (4.9% vs. 15-30%), because the study was retrospective, hence recorded only severe infections. We must actively seek infections in all hospitalized patients with HC, especially in the ones with decompensated cirrhosis and with upper GI bleeding.

Effectiveness of valganciclovir 900 mg versus 450 mg for cytomegalovirus prophylaxis in transplantation: direct and indirect treatment comparison meta-analysis.

BACKGROUND: valganciclovir (VGC) 900 mg is approved for CMV prophylaxis, but it has been associated with 10%-40% leucopenia rate. We hypothesize that VGC 450 mg daily may be as effective as and safer than 900 mg daily. METHODS: studies evaluating valganciclovir 900 mg and 450 mg daily against controls were evaluated. Direct comparisons were performed by random-effects models and indirect comparisons by the Bucher method. RESULTS: twelve trials with VGC 900 mg (1543 patients) and 8 trials with VGC 450 mg (1531 patients) were included. The risk of CMV disease with VGC 900 mg versus controls was 1.06 (95% confidence interval [CI], .64-1.76; P = .81; I2=29%) and with VGC 450 mg vs controls .77 (95%CI, .49-1.18; P = .23; I2=24%). The risk of leucopenia was 5.24 (2.09-13.15; P = .0004; I2=44%) for VGC 900 mg versus controls and 1.58 (.96-2.61; P = .07; I2=36%) for VGC 450 mg versus controls; the risk for acute allograft rejection was 1.71 (.45, -6.50; P = .43) for VGC 900 mg and .80 (.50-1.28; P = .34) for VGC 450 mg. Adjusted indirect comparison between VGC 900 mg and VGC 450mg: the risk for CMV disease was not significantly different: odds ratio (OR), 1.38 (.84-2.25); P = .19; the risk of leucopenia was significantly increased with VGC 900 mg: 3.32 (1.76-6.26); P = .0002; and the risk of rejection was significantly increased with VGC 900 mg: 2.56 (1.50-4.53); P = .0005. Results remained consistent after adjustments by allograft, CMV control strategy, and immunosuppression. CONCLUSIONS: valganciclovir 900 mg showed no superiority efficacy compared to controls (ganciclovir or preemptive) and equivalent efficacy to VGC 450 mg (statistical power: 94% and 97%, respectively) for CMV universal prophylaxis.VGC 900 mg was significantly associated with 3 times increase in the risk of leucopenia and 2 times increase in the risk of rejection compared with VGC 450 mg.