In Vitro Elution of Gentamicin from CERAMENT® G Has an Antimicrobial Effect on Bacteria With Various Levels of Gentamicin Resistance Found in Fracture-related Infection.

BACKGROUND: Fracture-related infection is a serious complication after trauma. CERAMENT® G combines dead-space management with local release of gentamicin in a single-stage procedure. Bacterial resistance against antibiotics is increasing. The local effect of CERAMENT® G on bacteria resistant to systemically administered gentamicin is unknown. QUESTIONS/PURPOSES: (1) What is the in vitro elution pattern of gentamicin from CERAMENT® G using a full washout model? (2) What is the in vitro antimicrobial activity (zone of inhibition) of CERAMENT® G against bacterial isolates found in fracture-related infection with different susceptibility levels toward gentamicin? METHODS: Elution of gentamicin from CERAMENT® G was determined in vitro over a period of 2 months. Elution experiments were performed in fivefold, with gentamicin being sampled in threefold at 19 different timepoints within 2 months. Antimicrobial activity was determined using the four most-frequently cultured bacterial species found in fracture-related infection: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Enterobacter cloacae . For each of the species, four different isolates with a different susceptibility to gentamicin were used. According to the European Committee on Antimicrobial Susceptibility Testing, the susceptibility of each isolate was classified into four different groups: fully susceptible (minimum inhibitory concentration 0.064 to 4 mg/L), minimally resistant (minimum inhibitory concentration 4 to 16 mg/L), moderately resistant (minimum inhibitory concentration 8 to 96 mg/L), and highly resistant (minimum inhibitory concentration 24 to 1024 mg/L), depending on each organism. The antimicrobial activity of CERAMENT® G was determined according to the European Committee on Antimicrobial Susceptibility Testing disk protocol. The experiment was performed in fivefold for each isolate. The zone of inhibition was compared between each bacterial isolate and within each of the four separate species. Nonlinear regression statistics were calculated between the zone of interest and logarithmic minimum inhibitory concentration for each bacterial species. RESULTS: After 24 hours, 95% of all available gentamicin was eluted, and gentamicin was still detectable after 2 months. CERAMENT® G showed antimicrobial activity against all bacterial species; only S taphylococcus aureus (with a minimum inhibitory concentration > 1024 mg/L) was not susceptible. The zone of interest of the different bacterial isolates was correlated with the logarithmic minimum inhibitory concentration. CONCLUSION: CERAMENT® G offers a bone substitute capable of releasing high levels of gentamicin within a short period of time. This study shows that CERAMENT® G has antimicrobial activity against bacterial isolates that are resistant to gentamicin when systemically administered. This finding raises the question of whether European Committee on Antimicrobial Susceptibility Testing cutoff points for systemic application are useful for the use of local CERAMENT® G. Standardized experiments to determine local antibiotic antimicrobial activity in fracture-related infection treatment are needed to form guidelines for the use of local antibiotics and ultimately improve fracture-related infection treatment. CLINICAL RELEVANCE: Local concentrations of gentamicin with CERAMENT® G are much higher than when systemically administered. It seems effective against certain bacterial strains that are not affected by systemically reachable concentrations of gentamicin. CERAMENT® G might still be effective when bacteria that are resistant to systemically administered concentrations of gentamicin are occulated from patients with fracture-related infection.

[A man with fever following laparotomy]. / Een man met koorts na een laparotomie.

An 80-year-old man had peritoneal metastases of a resected rectal carcinoma. Cytoreductive surgery was performed, with a wedge resection of the sigmoid colon. Postoperatively he developed subcutaneous emphysema of the neck. A CT scan showed a pneumoperitoneum with air in the mediastinum, due to leakage of the sigmoid colon.

Risk factors for infectious complications after open fractures; a systematic review and meta-analysis.

PURPOSE: The purpose of this study was to identify risk factors for the development of infection after open fracture fixation. METHODS: A comprehensive search in all scientific literature of the last 30 years was performed in order to identify patient-, trauma-, diagnosis- and treatment-related risk factors. Studies were included when infectious complications were assessed in light of one or more risk factors. A meta-analysis was performed. Risk ratios (RR) or risk differences (RD) with 95% confidence intervals were calculated. RESULTS: A total of 116 manuscripts were included. Male gender (RR 1.42), diabetes mellitus (DM) (RR 1.72), smoking (RR1.29), a lower extremity fracture (RR 1.94), Gustilo-Anderson grade III open fracture (RR 3.01), contaminated fracture (RR 7.85) and polytrauma patients (RR 1.49) were identified as statistically significant risk factors for the development of infectious complications. Of the treatment-related risk factors, only pulsatile lavage was associated with a higher infectious complication rate (RR 2.70). CONCLUSION: A number of risk factors for the development of infections after open fractures have been identified in the available literature. These factors should still be tested for independence in a multivariable model. Prospective, observational studies are needed to identify and quantify individual risk factors for infection after open fracture fixation.

Validating the WHO maternal near miss tool: comparing high- and low-resource settings.

BACKGROUND: WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. METHODS: Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria). Main outcome measures were prevalence of MNM criteria and case fatality rates (CFR). RESULTS: A total of 3172 women were studied; 2538 (80.0%) from the Netherlands, 248 (7.8%) from Tanzania and 386 (12.2%) from Malawi. Total SMO detection was 2767 (87.2%) for disease-based criteria, 2504 (78.9%) for intervention-based criteria and 1211 (38.2%) for organ dysfunction-based criteria. Including every woman who received ≥1 unit of blood in low-resource settings as life-threatening, as defined by organ dysfunction criteria, led to more equally distributed populations. In one third of all Dutch and Malawian maternal death cases, organ dysfunction criteria could not be identified from medical records. CONCLUSIONS: Applying solely organ dysfunction-based criteria may lead to underreporting of SMO. Therefore, a tool based on defining MNM only upon establishing organ failure is of limited use for comparing settings with varying resources. In low-resource settings, lowering the threshold of transfused units of blood leads to a higher detection rate of MNM. We recommend refined disease-based criteria, accompanied by a limited set of intervention- and organ dysfunction-based criteria to set a measure of severity.

Validating the WHO Maternal Near Miss Tool in a high-income country.

INTRODUCTION: This study was performed to assess the applicability of the WHO Maternal Near Miss Tool (MNM Tool) and the organ dysfunction criteria in a high-income country. MATERIAL AND METHODS: The MNM tool was applied to 2552 women who died of pregnancy-related causes or sustained severe acute maternal morbidity between August 2004 and August 2006 in one of the 98 hospitals with a maternity unit in the Netherlands. Fourteen (0.6%) cases had insufficient data for application. Each case was assessed according to the three main "MNM categories" specified in the MNM tool and their subcategory criteria: five disease-, four intervention- and seven organ dysfunction-based criteria. Potentially life-threatening conditions (disease-based inclusions) and life-threatening cases (organ dysfunction-based inclusions) were differentiated according to WHO methodology. Outcomes were incidence of all (sub)categories and case-fatality rates. RESULTS: Of the 2538 cases, 2308 (90.9%) women fulfilled disease-based, 2116 (83.4%) intervention-based and 1024 (40.3%) organ dysfunction-based criteria. Maternal death occurred in 48 women, of whom 23 (47.9%) fulfilled disease-based, 33 (68.8%) intervention-based and 31 (64.6%) organ dysfunction-based criteria. Case-fatality rates were 23/2308 (1.0%) for cases fulfilling the disease-based criteria, 33/2116 (1.6%) for intervention-based criteria and 31/1024 (3.0%) for women fulfilling the organ dysfunction-based criteria. CONCLUSIONS: In the Netherlands, where advanced laboratory and clinical monitoring are available, organ dysfunction-based criteria of the MNM tool failed to identify nearly two-thirds of sustained severe acute maternal morbidity cases and more than one-third of maternal deaths. Disease-based criteria remain important, and using only organ dysfunction-based criteria would lead to underestimating severe acute maternal morbidity.