Genomic reconstruction and directed interventions in a multidrug-resistant Shigellosis outbreak in Seattle, WA, USA: a genomic surveillance study.

BACKGROUND: Shigella spp have been associated with community-wide outbreaks in urban settings. We analysed a sustained shigellosis outbreak in Seattle, WA, USA, to understand its origins and mechanisms of antimicrobial resistance, define ongoing transmission patterns, and optimise strategies for treatment and infection control. METHODS: We did a retrospective study of all Shigella isolates identified from stool samples at the clinical laboratories at Harborview Medical Center and University of Washington Medical Center (Seattle, WA, USA) from May 1, 2017, to Feb 28, 2022. We characterised isolates by species identification, phenotypic susceptibility testing, and whole-genome sequencing. Demographic characteristics and clinical outcomes of the patients were retrospectively examined. FINDINGS: 171 cases of shigellosis were included. 78 (46%) patients were men who have sex with men (MSM), and 88 (52%) were people experiencing homelessness (PEH). Although 84 (51%) isolates were multidrug resistant, 100 (70%) of 143 patients with data on antimicrobial therapy received appropriate empirical therapy. Phylogenomic analysis identified sequential outbreaks of multiple distinct lineages of Shigella flexneri and Shigella sonnei. Discrete clonal lineages (ten in S flexneri and nine in S sonnei) and resistance traits were responsible for infection in different at-risk populations (ie, MSM, PEH), enabling development of effective guidelines for empirical treatment. The most prevalent lineage in Seattle was probably introduced to Washington State via international travel, with subsequent domestic transmission between at-risk groups. INTERPRETATION: An outbreak in Seattle was driven by parallel emergence of multidrug-resistant strains involving international transmission networks and domestic transmission between at-risk populations. Genomic analysis elucidated not only outbreak origin, but directed optimal approaches to testing, treatment, and public health response. Rapid diagnostics combined with detailed knowledge of local epidemiology can enable high rates of appropriate empirical therapy even in multidrug-resistant infection. FUNDING: None.

A Closer Look at the Laboratory Impact of Utilizing ePlex Blood Culture Identification Panels: a Workflow Analysis Using Rapid Molecular Detection for Positive Blood Cultures.

Rapid identification of pathogens is critical in bloodstream infections. We evaluated the diagnostic performance of the GenMark Dx ePlex blood culture identification (BCID) panels and the adoption of the ePlex system into the clinical laboratory workflow. Nonduplicate remnant specimens of positive blood cultures were prospectively tested using ePlex panels between January and March 2020. A total of 313 unique positive blood culture specimens were tested. The identified organisms consisted of 98 Gram-negative rods (GNR), 90 Gram-positive cocci (GPC) in clusters, 62 GPC in chains, 21 Gram-positive rods, and 20 yeasts; 22 organisms were off panel. The positive percent agreement was 100% across all organisms tested after discordancy resolution, while the negative percent agreement was 100% across all targets except Corynebacterium spp., where it was 99.7%. The ePlex BCID panels accurately detected 5 pan targets and 42 antimicrobial resistance gene markers, including 31 mecA, 4 vanA, 6 CTX-M, and 1 KPC gene. The median times to result were calculated as 2.5 h for Xpert MRSA/SA in GPC in clusters, 9.5 h for Accelerate Pheno (identification and susceptibility) in GNR, 6 h for peptide nucleic acid fluorescent in situ hybridization [PNA-FISH] in yeasts, 27 h for the latex agglutination test in S. aureus, 29 h for Lancefield serotyping in GPC in chains, and 29 h for Vitek-MS in GNR. In our laboratory, the ePlex panels could substantially reduce the time to result for bloodstream infection (BSI) caused by Streptococcus spp., Enterococcus spp., and Candida spp. The highly accurate ePlex panels can help streamline laboratory efficiency in the blood bench workflow, reducing the time to result for identification of BSI pathogens. IMPORTANCE Sepsis is a leading cause of morbidity and mortality worldwide. Rapid identification of the causative agent is of critical importance for the prompt initiation of the appropriate antibiotic treatment. In this study, we evaluated the diagnostic performance of the GenMark Dx ePlex blood culture identification (BCID) panels and their adoption into the clinical laboratory workflow. We prospectively tested 313 blood culture isolates and found that ePlex BCID panels had a positive percent agreement of 100% across all organisms tested after discordancy resolution. The negative percent agreement was 100% across all targets except Corynebacterium spp., where it was 99.7%. This new rapid technology (turnaround time of ~90 min) can help streamline laboratory efficiency in the blood bench workflow, reducing the time to result for identification of BSI pathogens. Adoption should be individualized based on the needs of the patient population and capabilities of the laboratory.

In-depth analysis of T2Bacteria positive results in patients with concurrent negative blood culture: a case series.

BACKGROUND: T2Bacteria assay uses T2 magnetic resonance (T2MR) technology for the rapid diagnosis of bacterial bloodstream infections (BSIs). This FDA cleared technology can detect 5 of the most prevalent pathogens causing bacteremia (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecium). Because the significance of discordant results between the T2Bacteria assay and blood culture (BC) remains a challenge, in this case series we reviewed the medical records of patients who had a positive T2Bacteria test and a concurrent negative BC. METHODS: Among 233 participants, we identified 20 patients with 21 (9%) discordant T2Bacteria-positive/BC-negative (T2+/BC-) results. We classified these results based on clinical cultures and clinical evidence. RESULTS: When we analyzed these 21 discordant results in-depth, 11 (52.5%) fulfilled criteria for probable BSI, 4 (19%) for possible BSI, and 6 (28.5%) were presumptive false positives. Among the probable/possible BSIs, discordant results were often associated with patients diagnosed with closed space and localized infections [pyelonephritis (n = 7), abscess (n = 4), pneumonia (n = 1), infected hematoma (n = 1), and osteomyelitis (n = 1)]. Also, within the preceding 2 days of the T2+/BC- blood sample, 80% (16/20) of the patients had received at least one dose of an antimicrobial agent which was active against the T2Bacteria-detected pathogen. CONCLUSIONS: In the majority of discrepant results, the T2Bacteria assay detected a plausible pathogen that was supported by clinical and/or microbiologic data. Discrepancies appear to be associated with closed space and localized infections and the recent use of effective antibacterial agents. The clinical significance and potential implications of such discordant results should be further investigated.

Diagnostic Accuracy of Presurgical Staphylococcus aureus PCR Assay Compared with Culture and Post-PCR Implementation Surgical Site Infection Rates.

Nasal colonization with Staphylococcus aureus is a well-referenced risk factor for postoperative surgical site infections (SSIs). Our health care system that performs >40,000 surgeries per year assessed both the diagnostic accuracy of the BD MAX StaphSR assay (MAX StaphSR), a PCR-based test that detects and differentiates S. aureus and methicillin-resistant S. aureus (MRSA), compared with our standard of care culture and the subsequent clinical impact on SSIs 1 year after implementation. In addition, residual specimens were tested by broth-enriched culture. Performance parameters for all methods were determined using latent class analysis. Direct culture was the least sensitive for S. aureus (85.1%) and MRSA (76.7%), whereas the MAX StaphSR assay and broth-enriched culture had similar sensitivities (96.7%) for MRSA. Prospective assessment using MAX StaphSR during a 1-year, postimplementation period revealed a lower rate of SSIs per 100 targeted surgeries (0.3) compared with MRSA-only screening (1.10) and no screening (2.28) (P < 0.05 for StaphSR versus MRSA-only screening and StaphSR versus no testing). MRSA and methicillin-sensitive S. aureus SSIs occurred equally (n = 14 each). The MAX StaphSR assay provided accurate detection of both S. aureus and MRSA nasal colonization in presurgical patients, allowing infection prevention measures, including presurgical prophylaxis, to be implemented in a timely and consistent manner to avoid SSIs.

The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients: A decision analytic model.

PURPOSE: Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. METHODS: A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. RESULTS: The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. DISCUSSION: Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

The Effect of Influenza Vaccination on Mortality and Risk of Hospitalization in Patients With Heart Failure: A Systematic Review and Meta-analysis.

BACKGROUND: Influenza is a major cause of morbidity and mortality in patients diagnosed with heart failure. The aim of this study was to evaluate the effectiveness of influenza vaccination in this population in terms of reduction in all-cause mortality and rate of hospitalization. METHODS: We conducted a systematic review and meta-analysis using PubMed and EMBASE entries from January of 2000 through April 2018. Publication bias was examined using the Egger's regression test. Statistical heterogeneity was examined using the Higgins I 2 statistic. Subgroup analyses were performed to examine the effect of vaccination during the influenza and noninfluenza seasons. RESULTS: We identified 8 studies that included a total of 82 354 patients with heart failure. In patients with heart failure who were vaccinated against influenza, we found a reduced risk of all-cause mortality (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51-0.87). No evidence of publication bias was found, and the effect was more pronounced during influenza season (HR, 0.49; 95% CI, 0.30-0.69), compared with noninfluenza season (HR, 0.79; 95% CI, 0.68-0.89). In terms of heart failure hospitalizations, we did not identify a statistically significant difference between the cohorts (HR, 0.62; 95% CI, 0.00-1.23). CONCLUSIONS: Influenza vaccination was associated with a decreased risk of all-cause mortality in patients with heart failure, and this effect was more prominent during the influenza season.

A Systematic Review and Meta-analysis of Antibiotic Treatment Duration for Bacteremia Due to Enterobacteriaceae.

The duration of antibiotic therapy for bacteremia due to Enterobacteriaceae is not well defined. We sought to evaluate the clinical outcomes with shorter- versus longer-course treatment. We performed a systematic search of the PubMed and EMBASE databases through May 2018. Studies presenting comparative outcomes between patients receiving antibiotic treatment for ≤10 days ("short-course") and those treated for >10 days ("long-course") were considered eligible. Four retrospective cohort studies and one randomized controlled trial comprising 2,865 patients met the inclusion criteria. The short- and long-course antibiotic treatments did not differ in 30-day all-cause mortality (1,374 patients; risk ratio [RR] = 0.99; 95% confidence interval [CI], 0.69 to 1.43), 90-day all-cause mortality (1,750 patients; RR = 1.16; 95% CI, 0.81 to 1.66), clinical cure (1,080 patients; RR = 1.02; 95% CI, 0.96 to 1.08), or relapse at 90 days (1,750 patients; RR = 1.08; 95% CI, 0.69 to 1.67). In patients with bacteremia due to Enterobacteriaceae, the short- and long-course antibiotic treatments did not differ significantly in terms of clinical outcomes. Further well-designed studies are needed before treatment for 10 days or less is adopted in clinical practice.

The Cost-Effectiveness of Corticosteroids for the Treatment of Community-Acquired Pneumonia.

BACKGROUND: The use of corticosteroids as adjunct treatment for community-acquired pneumonia (CAP) is associated with potential clinical benefits. The aim of this study was to evaluate the cost-effectiveness of this approach. METHODS: We constructed a decision-analytic model comparing the use of corticosteroids + antibiotics with that of placebo + antibiotics for the treatment of CAP. Cost-effectiveness was determined by calculating deaths averted and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. RESULTS: In the base-case analysis, corticosteroids + antibiotics resulted in savings of $142,795 per death averted. In the probabilistic analysis, at a willingness to pay of $50,000, corticosteroids + antibiotics had a 86.4% chance of being cost-effective compared with placebo + antibiotics. In cost-effectiveness acceptability curves, the corticosteroids + antibiotics strategy was cost-effective in 87.6% to 94.3% of simulations compared with the placebo + antibiotics strategy for a willingness to pay ranging from $0 to $50,000. In patients with severe CAP (Pneumonia Severity Index classes IV/V) the corticosteroids + antibiotics strategy resulted in savings of $70,587 and had a 82.6% chance of being cost-effective compared with the placebo + antibiotics strategy. CONCLUSIONS: The use of corticosteroids + antibiotics is a cost-effective strategy and results in considerable health care cost-savings, especially among patients with severe CAP (Pneumonia Severity Index classes IV/V).

Colistin resistance in carbapenemase-producing Klebsiella pneumoniae bloodstream isolates: Evolution over 15 years and temporal association with colistin use by time series analysis.

Colistin is often the only available treatment option against infections caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp). In this study, the evolution of colistin resistance among CP-Kp and its relationship with colistin use in a tertiary-care hospital in Athens, Greece, was investigated. All CP-Kp blood isolates recovered between January 2002 and June 2016 were tested for susceptibility to colistin by agar dilution and broth microdilution methods. Data on colistin use were collected from the pharmacy database. Time series of colistin use and resistance were analysed using the Box and Jenkins method. A transfer function model was built to quantify the dynamic relationship between colistin use and resistance. Overall, 313 CP-Kp isolates were identified. The percentage colistin resistance increased from 0% in 2002 to 26.9% in 2016 (R2 = 0.5, P < 0.01). A temporal association between colistin use and resistance was observed; an increase in colistin use by 1 DDD/100 patient-days led to a 0.05 increase in the incidence rate of colistin resistance. The time lag between the effect of colistin use on subsequent variations in colistin resistance was 3 months. Colistin use and prior levels of colistin resistance could explain 69% of colistin resistance; in the remaining 31%, other factors might have played a role. The results presented here demonstrate a significant temporal association between colistin use and colistin resistance. These findings have important implications in implementing strategies to contain colistin resistance.

Systematic Review and Meta-analysis of the Efficacy of Short-Course Antibiotic Treatments for Community-Acquired Pneumonia in Adults.

The duration of therapy for community-acquired pneumonia (CAP) remains undefined. We sought to investigate whether short-course antibiotic treatment for CAP is associated with favorable clinical outcomes in adult patients. We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies comparing the effectiveness and safety between treatment regimens administered for ≤6 days and ≥7 days. We defined treatment for ≤6 days as short-course treatment and treatment for ≥7 days as long-course treatment. Twenty-one clinical trials (4,861 clinically evaluable patients) were included, and 19 out of 21 trials were randomized. Clinical cure was similar between the compared groups (4,069 patients, risk ratio [RR] = 0.99 [95% confidence interval {CI}, 0.97 to 1.01]), irrespective of patient setting (RR = 0.98 [95% CI, 0.96 to 1.00] for the outpatient setting and RR = 1.00 [95% CI, 0.92 to 1.09] for the inpatient setting) or severity of pneumonia (RR = 1.05 [95% CI, 0.96 to 1.14]). Also, relapses were similar between the short- and long-course treatment groups (1,923 patients, RR = 0.67 [95% CI, 0.30 to 1.46]). Short-course treatment was associated with fewer serious adverse events (1,923 patients, RR = 0.73 [95% CI, 0.55 to 0.97]) and, importantly, resulted in lower mortality than long-course treatment (2,802 patients, RR = 0.52 [95% CI, 0.33 to 0.82]). In CAP, short-course antibiotic treatment (≤6 days) is as effective as and potentially superior to, in terms of mortality and serious adverse events, longer-course treatment.

Impact of oseltamivir use on the reduction of complications in patients with influenza: a prospective study.

To evaluate the factors associated with oseltamivir prescription and to study the effectiveness of oseltamivir in reducing influenza-related complications. A prospective cohort study using the SOS Doctors (a network of physicians who perform house-call visits in Attica, Greece). Patients with confirmed or clinically suspected influenza were followed up to 14 days during the 2011-2012 influenza period. 410 patients with confirmed or suspected influenza were included. Healthy adults were mainly enrolled, with a median age of 44 years. Influenza diagnosis was mainly based on clinical criteria (65.8 % of patients). Oseltamivir was prescribed for 45.4 % of them. In a multivariate analysis, prescription of oseltamivir was associated with the attending physician (p < 0.001), positive influenza test (p < 0.001) and diabetes (p = 0.027). Data on complications were available for 351 patients, and 50 (15.8 %) of them reported at least one. Seven patients required hospitalization. Types of complications (pneumonia, bronchitis, etc.) were not significantly different between patients receiving and those not receiving oseltamivir. In the multivariate analysis, higher oseltamivir prescription rate was associated with fewer complications (p < 0.001). Bearing in mind the limitations of a non-randomized study, in a real-life setting, oseltamivir prescription and the rate of complications in patients with influenza were associated with the attending physician, underlying diseases and diagnostic tests. Overall, when the frequency of oseltamivir prescription increased, the influenza-related complications decreased.

Antimicrobial-impregnated and -coated shunt catheters for prevention of infections in patients with hydrocephalus: a systematic review and meta-analysis.

OBJECT The aim of this study was to evaluate the effectiveness of antimicrobial-impregnated and -coated shunt catheters (antimicrobial catheters) in reducing the risk of infection in patients undergoing CSF shunting or ventricular drainage. METHODS The PubMed and Scopus databases were searched. Catheter implantation was classified as either shunting (mainly ventriculoperitoneal shunting) or ventricular drainage (mainly external [EVD]). Studies evaluating antibioticimpregnated catheters (AICs), silver-coated catheters (SCCs), and hydrogel-coated catheters (HCCs) were included. A random effects model meta-analysis was performed. RESULTS Thirty-six studies (7 randomized and 29 nonrandomized, 16,796 procedures) were included. The majority of data derive from studies on the effectiveness of AICs, followed by studies on the effectiveness of SCCs. Statistical heterogeneity was observed in several analyses. Antimicrobial shunt catheters (AICs, SCCs) were associated with lower risk for CSF catheter-associated infections than conventional catheters (CCs) (RR 0.44, 95% CI 0.35-0.56). Fewer infections developed in the patients treated with antimicrobial catheters regardless of randomization, number of participating centers, funding, shunting or ventricular drainage, definition of infections, de novo implantation, and rate of infections in the study. There was no difference regarding gram-positive bacteria, all staphylococci, coagulase-negative streptococci, and Staphylococcus aureus, when analyzed separately. On the contrary, the risk for methicillin-resistant S. aureus (MRSA, RR 2.64, 95% CI 1.26-5.51), nonstaphylococcal (RR 1.75, 95% CI 1.22-2.52), and gram-negative bacterial (RR 2.13, 95% CI 1.33-3.43) infections increased with antimicrobial shunt catheters. CONCLUSIONS Based on data mainly from nonrandomized studies, AICs and SCCs reduce the risk for infection in patients undergoing CSF shunting. Future studies should evaluate the higher risk for MRSA and gram-negative infections. Additional trials are needed to investigate the comparative effectiveness of the different types of antimicrobial catheters.

Compliance with once-daily versus twice or thrice-daily administration of antibiotic regimens: a meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate whether compliance of patients to antibiotic treatment is better when antibiotics are administered once than multiple times daily. METHODS: We performed a systematic search in PubMed and Scopus databases. Only randomized controlled trials were considered eligible for inclusion. Compliance to antibiotic treatment was the outcome of the meta-analysis. RESULTS: Twenty-six studies including 8246 patients with upper respiratory tract infections in the vast majority met the inclusion criteria. In total, higher compliance was found among patients treated with once-daily treatment than those receiving treatment twice, thrice or four times daily [5011 patients, RR=1.22 (95% CI, 1.11, 1.34]. Adults receiving an antibiotic once-daily were more compliant than those receiving the same antibiotic multiple times daily [380 patients, RR=1.09 (95% CI, 1.02, 1.16)]. Likewise, children that received an antibiotic twice-daily were more compliant than those receiving the same antibiotic thrice-daily [2118 patients, RR=1.10 (95% CI, 1.02, 1.19)]. Higher compliance was also found among patients receiving an antibiotic once compared to those receiving an antibiotic of different class thrice or four times daily [395 patients, RR=1.20 (95% CI, 1.12, 1.28)]. The finding of better compliance with lower frequency daily was consistent regardless of the study design, and treatment duration. CONCLUSION: This meta-analysis showed that compliance to antibiotic treatment might be associated with higher when an antibiotic is administered once than multiple times daily for the treatment of specific infections and for specific classes of antibiotics.

Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBeAg- mothers: a systematic review and meta-analysis.

OBJECTIVES: The cost-effectiveness of augmenting immunization against hepatitis B infection with hepatitis B immunoglobulin (HBIG) remains controversial, particularly for the subpopulation of babies of HBsAg+/HBeAg- mothers that are considered as low-infective. We aimed to evaluate the effectiveness of vaccine alone compared with vaccine plus HBIG for the immunization of babies of HBsAg+/HBeAg- mothers. METHODS: We searched PubMed, Scopus and Cochrane Central Register of Controlled Trials databases to identify studies comparing the effectiveness of combined immunization (vaccine plus HBIG) with vaccine alone in neonates of HBsAg+/HBeAg- mothers. A systematic review and meta-analysis of eligible studies was performed. RESULTS: A total of nine eligible studies were identified (four randomized controlled trials). No difference was found regarding the primary outcome of our meta-analysis, namely occurrence of hepatitis B infection, between neonates who received vaccine only, compared with those who received both vaccine and HBIG (four studies, 3426 patients, OR=0.82, 95% CI=0.41-1.64). This finding was consistent with regards to seroprotection rate (four studies, 1323 patients, OR=1.24, 95% CI=0.97-1.58). Safety data were not reported in the included studies. CONCLUSIONS: The available limited published evidence suggests that vaccine alone seems to be equally effective to the combination of HBIG and hepatitis B vaccine for neonates of HBsAg+/HBeAg- mothers in preventing infection. Further studies are needed in order to clarify the potential benefit of combined immunization to this specific subgroup of patients.

Determination of MIC distribution of arbekacin, cefminox, fosfomycin, biapenem and other antibiotics against gram-negative clinical isolates in South India: a prospective study.

OBJECTIVES: To determine the in vitro activity of antibiotics, including arbekacin, cefminox, fosfomycin and biapenem which are all still unavailable in India, against Gram-negative clinical isolates. METHODS: We prospectively collected and tested all consecutive isolates of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. from blood, urine and sputum samples between March and November 2012. The minimum inhibition concentration (MIC) of 16 antibiotics was determined by the broth micro-dilution method. RESULTS: Overall 925 isolates were included; 211 E. coli, 207 Klebsiella spp., 153 P. aeruginosa, and 354 Acinetobacter spp. The MIC50 and MIC90 were high for cefminox, biapenem and arbekacin for all pathogens but interpretative criteria were not available. The MIC50 was categorized as susceptible for a couple of antibiotics, including piperacillin/tazobactam, carbapenems and amikacin, for E. coli, Klebsiella spp. and P. aeruginosa. However, for Acinetobacter spp., the MIC50 was categorized as susceptible only for colistin. On the other hand, fosfomycin was the only antibiotic that inhibited 90% of E. coli and Klebsiella spp. isolates, while 90% of P. aeruginosa isolates were inhibited only by colistin. Finally, 90% of Acinetobacter spp. isolates were not inhibited by any antibiotic tested. CONCLUSION: Fosfomycin and colistin might be promising antibiotics for the treatment of infections due to E. coli or Klebsiella spp. and P. aeruginosa, respectively, in India; however, clinical trials should first corroborate the in vitro findings. The activity of tigecycline should be evaluated, as this is commonly used as last-resort option for the treatment of multidrug-resistant Acinetobacter infections.

Deaths attributable to carbapenem-resistant Enterobacteriaceae infections.

We evaluated the number of deaths attributable to carbapenem-resistant Enterobacteriaceae by using studies from around the world published before April 9, 2012. Attributable death was defined as the difference in all-cause deaths between patients with carbapenem-resistant infections and those with carbapenem-susceptible infections. Online databases were searched, and data were qualitatively synthesized and pooled in a metaanalysis. Nine studies met inclusion criteria: 6 retrospective case-control studies, 2 retrospective cohort studies, and 1 prospective cohort study. Klebsiella pneumoniae was the causative pathogen in 8 studies; bacteremia was the only infection in 5 studies. We calculated that 26%-44% of deaths in 7 studies were attributable to carbapenem resistance, and in 2 studies, which included bacteremia and other infections, -3% and -4% of deaths were attributable to carbapenem resistance. Pooled outcomes showed that the number of deaths was significantly higher in patients with carbapenem-resistant infections and that the number of deaths attributable to carbapenem resistance is considerable.

Use of negative-pressure wound therapy in breast tissues: evaluation of the literature.

BACKGROUND: Negative-pressure wound therapy (NPWT) has been suggetsed to have a positive impact on the healing of sternal or extremity wounds. However, few data deriving from breast surgery have been published. We evaluated the available literature regarding the effectiveness of NPWT systems in the healing of breast tissues. METHODS: The PubMed and Scopus databases were searched systematically, and all studies that provided relevant data were considered eligible for inclusion in the review. Twenty studies (154 female patients) met the inclusion criteria (four cohort studies, one case series, and 15 case reports). RESULTS: The NPWT system was used alone in 17 patients and in combination with other techniques in the remaining 137. The lesion was secondary to plastic surgery in 107 women, other operations in 40 women (38 of them for breast cancer), and primary breast infection in seven women. Infections (including necrotizing fasciitis), pyoderma gangrenosum, and necrosis were among the most common complications for which NPWT was used. In total, 150 of 154 patients receiving NPWT healed completely. Two patients died before complete closure for reasons unrelated to the wound, and NPWT failed in two patients who healed later with muscle flap coverage. CONCLUSION: The scant published evidence suggests that NPWT systems might be useful in the healing of complicated breast wounds. However, larger studies are needed to investigate the effectiveness of this system further before it is established in breast surgery.