What Happens After Discharge? A 2+ Year Follow-Up After Laparoscopic Subtotal Fenestrating and Reconstituting Cholecystectomy.

Laparoscopic subtotal cholecystectomy (LSC) is utilized to prevent complications in the difficult cholecystectomy. Medium-term outcomes are poorly studied for fenestrating and reconstituting operative techniques. A single-institution retrospective review was undertaken of all LSCs. A telephone survey was used to identify complications addressed at other institutions. We performed subgroup analyses by operative approach and of patients requiring postoperative endoscopic intervention (ERC). 28 patients met inclusion criteria. The median follow-up was 32.7 months. There were no bile duct injuries or reoperations. 21% of patients required a postoperative ERC and 50% were discharged home with a drain. Bile leaks were found to be more prevalent in the fenestrating LSC group (38% vs 0%, P = .003). The case series suggested more severe recurrent biliary disease in patients undergoing reconstituting LSC. Laparoscopic subtotal cholecystectomy appears to have satisfactory medium-term outcomes. The reconstituting LSC group trends toward more severe recurrent disease which warrants further investigation.

Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection.

BACKGROUND: Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide, with Mycobacterium avium complex (MAC) and Mycobacterium abscessus as the predominant pathogens. Current treatments are poorly tolerated and modestly effective, highlighting the need for new treatments. SPR719, the active moiety of the benzimidazole prodrug SPR720, inhibits the ATPase subunits of DNA gyrase B, a target not exploited by current antibiotics, and therefore, no cross-resistance is expected with standard-of-care (SOC) agents. OBJECTIVES: To evaluate the in vitro activity of SPR719 against MAC and M. abscessus clinical isolates, including those resistant to SOC agents, and in vivo efficacy of SPR720 in murine non-tuberculous mycobacteria (NTM) pulmonary infection models. METHODS: NTM isolates were tested for susceptibility to SPR719. Chronic C3HeB/FeJ and severe combined immunodeficient murine models of pulmonary infection were used to assess efficacy of SPR720 against MAC and M. abscessus, respectively. RESULTS: SPR719 was active against MAC (MIC90, 2 mg/L) and M. abscessus (MIC90, 4 mg/L) clinical isolates. Efficacy of SPR720 was demonstrated against MAC pulmonary infection, both as a monotherapy and in combination with SOC agents. SPR720 monotherapy exhibited dose-dependent reduction in bacterial burden, with the largest reduction observed when combined with clarithromycin and ethambutol. Efficacy of SPR720 was also demonstrated against M. abscessus pulmonary infection where monotherapy exhibited a dose-dependent reduction in bacterial burden with further reductions detected when combined with SOC agents. CONCLUSIONS: In vitro activity of SPR720 against common NTM pathogens and efficacy in murine infections warrant the continued clinical evaluation of SPR720 as a new oral option for the treatment of NTM-PD.

Are enhanced recovery protocols after pancreatoduodenectomy still efficient when applied in elderly patients? A systematic review and individual patient data meta-analysis.

BACKGROUND: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD). METHODS: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70-79 years) and older patients (≥80 years). RESULTS: IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65-1.29], p = .596 and OR 1.22 [95% CI: 0.61-2.46], p = .508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (-0.14 days [95% CI: -0.29 to 0.01], p = .071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (-0.28 days [95% CI: -0.62 to 0.05], p = .069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (-0.36 days [95% CI: -0.71 to -0.004], p = .048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group. CONCLUSION: ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers.

Minocycline and the SPR741 Adjuvant Are an Efficacious Antibacterial Combination for Acinetobacter baumannii Infections.

Antibiotic resistance, when it comes to bacterial infections, is not a problem that is going to disappear anytime soon. With the lack of larger investment in novel antibiotic research and the ever-growing increase of resistant isolates amongst the ESKAPEE pathogens (Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus sp., and Escherichia coli), it is inevitable that more and more infections caused by extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains will arise. One strategy to counteract the growing threat is to use antibiotic adjuvants, a drug class that on its own lacks significant antibiotic activity, but when mixed with another antibiotic, can potentiate increased killing of bacteria. Antibiotic adjuvants have various mechanisms of action, but polymyxins and polymyxin-like molecules can disrupt the Gram-negative outer membrane and allow other drugs better penetration into the bacterial periplasm and cytoplasm. Previously, we showed that SPR741 had this adjuvant effect with regard to rifampin; however, rifampin is often not used clinically because of easily acquired resistance. To find additional, appropriate clinical partners for SPR741 with respect to pulmonary and wound infections, we investigated tetracyclines and found a previously undocumented synergy with minocycline in vitro and in vivo in murine models of infection.

National recurrence of pancreatitis and readmissions after biliary pancreatitis.

BACKGROUND: National and international guidelines support early cholecystectomy after mild gallstone pancreatitis but a recent nationwide study suggested these recommendations are not universally followed. Our study sought to quantify the national utilization of same hospitalization cholecystectomy versus non-operative management (NOM) and its association with pancreatitis recurrence, readmissions, and costs after mild gallstone pancreatitis (GP). METHODS: Adult patients admitted with mild GP were identified from the Nationwide Readmission Database 2010-2015. Primary outcomes included the rate of cholecystectomy during the index admission as well as pancreatitis recurrence and readmission at 30 and 180 days (30d, 180d) comparing NOM to same hospitalization cholecystectomy. Mortality upon readmission, total length of stay (LOS), and total costs (combined index-readmission hospital costs) were also explored. Cox proportional hazards regression and generalized linear models controlled for patient/hospital confounders. RESULTS: Among the 65,067 patients identified, 30% underwent cholecystectomy. The NOM cohort was older (58 vs. 50 years), had more comorbidities (Charlson index > 2, 23.5% vs. 11.5%), fewer female patients (56.7% vs. 67%) and less discharge-to-home (84.9% vs. 94.4%) (all p < 0.001). NOM was associated with increase in recurrence and unplanned readmissions at 30d [Hazard Ratio 3.53 (95% CI 2.92-4.27), 2.41 (2.11-2.74), respectively], and 180d [4.27 (3.65-4.98), 2.78 (2.54-3.04), respectively], as well as increased mortality during 180d readmission 1.88 (1.06-3.35). This approach was also associated with significant increase in LOS [predicted mean difference 2.79 days (95% CI 2.46-3.12)] and total costs [$2507.89 ($1714.4-$3301.4)]. CONCLUSIONS: In the USA, most patients presenting with mild GP do not undergo same hospitalization cholecystectomy. This strategy results in higher recurrent pancreatitis, mortality during readmission, and an additional $4.85 M/year in hospital costs nationwide. These data support same hospitalization cholecystectomy as the gold standard for mild GP.

Impact of enhanced recovery protocols after pancreatoduodenectomy: meta-analysis.

BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.

Enhanced recovery protocols consist of interdisciplinary interventions aimed at standardizing care and reducing the impact of surgical stress. They often include a short period of preoperative fasting during the night before surgery, early removal of lines and surgical drains, early food intake and mobilization out of bed on the day of surgery. This study gives a summary of reports assessing such care protocols in patients undergoing pancreatic head surgery, and assesses the impact of these protocols on functional recovery in an analysis of individual-patient data. The study revealed the true benefits of enhanced recovery protocols, including shorter time to food intake, earlier bowel activity, fewer complications after surgery, and a shorter hospital stay compared with conventional care.

In Vitro and In Vivo Characterization of Tebipenem (TBP), an Orally Active Carbapenem, against Biothreat Pathogens.

Bacillus anthracis and Yersinia pestis, causative pathogens for anthrax and plague, respectively, along with Burkholderia mallei and B. pseudomallei are potential bioterrorism threats. Tebipenem pivoxil hydrobromide (TBP HBr, formerly SPR994), is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) gram-negative pathogens, including quinolone-resistant and extended-spectrum-ß-lactamase-producing Enterobacterales. We evaluated the in vitro activity and in vivo efficacy of tebipenem against biothreat pathogens. Tebipenem was active in vitro against 30-strain diversity sets of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei with minimum inhibitory concentration (MIC) values of 0.001 - 0.008 µg/ml for B. anthracis, ≤0.0005 - 0.03 µg/ml for Y. pestis, 0.25 - 1 µg/ml for B. mallei, and 1 - 4 µg/ml for B. pseudomallei In a B. anthracis murine model, all control animals died within 52 h post challenge. The survival rates in the groups treated with tebipenem were 75% and 73% when dosed at 12 h and 24 h post challenge, respectively. The survival rates in the positive control groups treated with ciprofloxacin were 75% and when dosed 12 h and 25% when dosed 24 h post challenge, respectively. Survival rates were significantly (p=0.0009) greater in tebipenem groups treated at 12 h and 24 h post challenge and in the ciprofloxacin group 12 h post-challenge vs. the vehicle-control group. For Y. pestis, survival rates for all animals in the tebipenem and ciprofloxacin groups were significantly (p<0.0001) greater than the vehicle-control group. These results support further development of tebipenem for treating biothreat pathogens.

Resistance among urinary tract pathogens collected in Europe during 2018.

OBJECTIVES: Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are urinary tract infection (UTI) pathogens and extended spectrum ß-lactamase (ESBL)-producing pathogens exhibit co-resistance to oral fluoroquinolones (FQ) and trimethoprim-sulphamethoxazole (TMP-SMX). This study assessed the prevalence of ESBL phenotypes and co-resistance to FQ and TMP-SMX. METHODS: In total, 766 E. coli, 260 K. pneumoniae and 104 P. mirabilis from UTIs in 18 countries were evaluated for susceptibility in the SENTRY surveillance programme, and results interpreted using EUCAST criteria. RESULTS: E. coli, K. pneumoniae and P. mirabilis accounted for 57.1%, 11.3% and 7.8%, respectively, of the isolates. Among E. coli, resistance to levofloxacin and TMP-SMX ranged from 21.8% to 32.7% for all isolates increasing to 66.5-67.0% among those with a ESBL phenotype (17.9% of all UTI E. coli from Europe were ESBL phenotypes). In contrast, all E. coli were susceptible to meropenem. For K. pneumoniae, resistance rates for levofloxacin and TMP-SMX were 32.2-40.0% increasing to 69.1-78.6% for ESBL phenotypes. Meropenem was the most active agent, with 7.7% resistance. Among P. mirabilis resistance to levofloxacin and TMP-SMX was 26-38.5% and increased to 100% for ESBL phenotypes. No meropenem-resistant P. mirabilis were reported. CONCLUSIONS: High co-resistance rates were observed for oral antibiotics among ESBL phenotypes raising concerns regarding empiric use of FQ and TMP-SMX for treating resistant UTIs outside of the hospital. In contrast, intravenous carbapenems retain activity against resistant UTI pathogens. New oral options with the spectrum of the carbapenems would address an unmet need for managing resistant UTIs.

Achalasia and obesity: patient outcomes and impressions following laparoscopic Heller myotomy and Dor fundoplication.

PURPOSE: The optimal management of achalasia in obese patients is unclear. For those who have undergone Heller myotomy and fundoplication, the long-term outcomes and their impressions following surgery are largely unknown. METHODS: A retrospective review of patients who underwent laparoscopic Heller myotomy and Dor fundoplication (LHMDF) for achalasia was performed. From this cohort, Class 2 and 3 obese (BMI > 35 kg/m2) patients were identified for short- and long-term outcome analysis. RESULTS: Between 2003 and 2015, 252 patients underwent LHMDF for achalasia, and 17 (7%) patients had BMI > 35 kg/m2. Pre-operative Eckardt scores varied from 2 to 9, and at short-term (2-4 week) follow-up, scores were 0 or 1. Ten (58%) patients had available long-term (2-144 months) follow-up data. Eckardt scores at this time ranged from 0 to 6. Symptom recurrence was worse for patients with BMI > 40 kg/m2 compared to patients with BMI < 40 kg/m2. BMI was largely unchanged at long-term follow-up regardless of pre-intervention BMI. Most patients were satisfied with surgery but would have considered a combined LHMDF and weight-loss procedure had it been offered. CONCLUSION: LHMDF for achalasia in obese patients is safe and effective in the short term. At long-term follow-up, many patients had symptom recurrence and experienced minimal weight loss. Discussing weight-loss surgery at the time LHMDF may be appropriate to ensure long-term achalasia symptom relief.

In Vitro and In Vivo Characterization of Tebipenem, an Oral Carbapenem.

The continued evolution of bacterial resistance to the ß-lactam class of antibiotics has necessitated countermeasures to ensure continued effectiveness in the treatment of infections caused by bacterial pathogens. One relatively successful approach has been the development of new ß-lactam analogs with advantages over prior compounds in this class. The carbapenems are an example of such ß-lactam analogs possessing improved stability against ß-lactamase enzymes and, therefore, a wider spectrum of activity. However, all carbapenems currently marketed for adult patients are intravenous agents, and there is an unmet need for an oral agent to treat patients that otherwise do not require hospitalization. Tebipenem pivoxil hydrobromide (tebipenem-PI-HBr or SPR994) is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) Gram-negative pathogens, including quinolone-resistant and extended-spectrum-ß-lactamase-producing Enterobacterales Tebipenem-PI-HBr is currently in development for the treatment of complicated urinary tract infections (cUTI). Microbiological data are presented here that demonstrate equivalency of tebipenem with intravenous carbapenems such as meropenem and support its use in infections in which the potency and spectrum of a carbapenem are desired. The results from standard in vitro microbiology assays as well as efficacy in several in vivo mouse infection models suggest that tebipenem-PI-HBr could be a valuable oral agent available to physicians for the treatment of infections, particularly those caused by antibiotic-resistant Gram-negative pathogens.

Advancement of GyrB Inhibitors for Treatment of Infections Caused by Mycobacterium tuberculosis and Non-tuberculous Mycobacteria.

The prospect of ever increasing antibiotic resistance eroding currently available treatment options for bacterial infections underscores the need to continue to identify new antibiotics, preferably those that act on novel targets or with novel mechanisms of action. Bacterial gyrase B subunit (GyrB), an essential component of bacterial gyrase required for successful DNA replication, represents such a target. We describe recent examples of GyrB inhibitors and point out their potential utility for treatment of mycobacterial diseases caused by Mycobacterium tuberculosis (TB) and non-tuberculous mycobacteria (NTM). Current therapeutic options for these diseases are often suboptimal due to resistance to current standard of care antibiotics. A future GyrB inhibitor-based antibiotic could offer a new and effective addition to the armamentarium for treatment of mycobacterial diseases and possibly for infections caused by other bacterial pathogens. One GyrB inhibitor, SPR720, has recently completed a first-in-human clinical trial and is in clinical development for the treatment of NTM and TB infections.

Patients support transfer of care for unexpected findings in laparoscopic cholecystectomy.

INTRODUCTION: Surgeons often assume patients may be dissatisfied if their operations were stopped due to suspicious intraoperative findings requiring transfer of care. We sought to assess patient opinions regarding transfer of care for unexpected intraoperative findings during laparoscopic cholecystectomy with and without bile duct injury (BDI). METHODS AND PROCEDURES: The investigators developed two clinical scenarios comparing transfer of care for unexpected intraoperative findings during elective laparoscopic cholecystectomy: without BDI and with BDI requiring open repair. A multi-institutional structured telephone interview process was conducted with patients ≥ 18 years of age who had an outpatient, uncomplicated laparoscopic cholecystectomy within the last year. The first scenario presented a case of suspicious findings prompting the surgeon to stop and transfer for specialized care; whereas the second case was a BDI requiring transfer of care. Textual and thematic analysis as well as descriptive statistics was used for analysis, with significance set at p < 0.05. RESULTS: Forty-five patients completed the survey. Satisfaction with transfer of care for unexpected intraoperative findings without BDI was 69%, and over 95% of respondents were satisfied their surgeon stopped the procedure to initiate transfer due to safety concerns; 64% of patients would return to that surgeon for postoperative care; and 78% would see that surgeon again. In the scenario with BDI requiring open repair, 86% were satisfied with their surgeon's decision to stop the operation; 91% of patients were satisfied with transfer of care; and 32% would see their first surgeon again. Themes of prioritizing safety and transparency were frequently cited. CONCLUSIONS: Patients prioritize safety and are satisfied with halting a procedure to facilitate transfer of care for suspicious intraoperative findings during routine laparoscopic cholecystectomy.

The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017.

Urinary tract infections (UTIs) caused by Escherichia coli have been historically managed with oral antibiotics including the cephalosporins, fluoroquinolones and trimethoprim-sulfamethoxazole. The use of these agents is being compromised by the increase in extended spectrum ß-lactamase (ESBL)-producing organisms, mostly caused by the emergence and clonal expansion of E. coli multilocus sequence typing (ST) 131. In addition, ESBL isolates show co-resistance to many of oral agents. Management of UTIs caused by ESBL and fluoroquinolone-resistant organisms is becoming increasingly challenging to treat outside of the hospital setting with clinicians having to resort to intravenous agents. The aim of this study was to assess the prevalence of ESBL phenotypes and genotypes among UTI isolates of E. coli collected in the US during 2017 as well as the impact of co-resistance to oral agents such as the fluoroquinolones and trimethoprim-sulfamethoxazole. The national prevalence of ESBL phenotypes of E. coli was 15.7% and was geographically distributed across all nine Census regions. Levofloxacin and trimethoprim-sulfamethoxazole-resistance rates were ≥ 24% among all isolates and this co-resistance phenotype was considerably higher among isolates showing an ESBL phenotype (≥ 59.2%) and carrying blaCTX-M-15 (≥ 69.5%). The agents with the highest potency against UTI isolates of E. coli, including ESBL isolates showing cross-resistance across oral agents, were the intravenous carbapenems. The results of this study indicate that new oral options with the spectrum and potency similar to the intravenous carbapenems would address a significant unmet need for the treatment of UTIs in an era of emergence and clonal expansion of ESBL isolates resistant to several classes of antimicrobial agents, including oral options.

Optimal timing and route of nutritional support after esophagectomy: A review of the literature.

Some controversy surrounds the postoperative feeding regimen utilized in patients who undergo esophagectomy. Variation in practices during the perioperative period exists including the type of nutrition started, the delivery route, and its timing. Adequate nutrition is essential for this patient population as these patients often present with weight loss and have altered eating patterns after surgery, which can affect their ability to regain or maintain weight. Methods of feeding after an esophagectomy include total parenteral nutrition, nasoduodenal/nasojejunal tube feeding, jejunostomy tube feeding, and oral feeding. Recent evidence suggests that early oral feeding is associated with shorter LOS, faster return of bowel function, and improved quality of life. Enhanced recovery pathways after surgery pathways after esophagectomy with a component of early oral feeding also seem to be safe, feasible, and cost-effective, albeit with limited data. However, data on anastomotic leaks is mixed, and some studies suggest that the incidence of leaks may be higher with early oral feeding. This risk of anastomotic leak with early feeding may be heavily modulated by surgical approach. No definitive data is currently available to definitively answer this question, and further studies should look at how these early feeding regimens vary by surgical technique. This review aims to discuss the existing literature on the optimal route and timing of feeding after esophagectomy.

Perioperative Outcomes and Quality of Life after Repair of Recurrent Hiatal Hernia Are Compromised Compared with Primary Repair.

Paraesophageal hernia repair (PEHR) is burdened by high recurrence rates that frequently lead to redo PEHR. Revisional surgery, because of higher complexity, higher risk of injury, and the intrinsic risk of recurrence, has increased likelihood of higher complication rates and decreased quality of life (QOL) postoperatively. We aimed to compare perioperative outcomes and QOL after revisional and primary PEHR. A retrospective review of all patients who underwent PEHR for a recurrent hernia between January 2011 and July 2016 was completed. These were matched with a contemporary cohort of patients who underwent primary PEHR by age, gender, and BMI. Perioperative measures were compared. The patients were invited to complete the Gastrointestinal Quality of Life Index (GIQLI) to assess response to surgical intervention. There were 24 patients (group 1) who underwent revisional PEHR, and they were matched to 48 patients (group 2) who had a primary hernia repair. Thirteen patients in group 1 responded to the survey (54%), whereas 21 patients' responses were received from group 2 (44%). Conversion rates, LOS, and mean Gastrointestinal Quality of Life Index scores were significantly different between the two groups. Reoperative procedures for paraesophageal and hiatal hernias are burdened by higher conversion rates and length of stay, with similar overall complication rates. Patients who are undergoing repair of a recurrent hernia should be preoperatively counseled, and should have realistic expectations of their GI QOL after surgery.

Preoperative anemia: a common finding that predicts worse outcomes in patients undergoing primary hiatal hernia repair.

BACKGROUND: The increased incidence of anemia in patients with hiatal hernias (HH) and resolution of anemia after HH repair (HHR) have been clearly demonstrated. However, the implications of preoperative anemia on postoperative outcomes have not been well described. In this study, we aimed to identify the incidence of preoperative anemia in patients undergoing primary HHR at our institution and sought to determine whether preoperative anemia had an impact on postoperative outcomes. METHODS: Using our IRB-approved institutional HH database, we retrospectively identified patients undergoing primary HHR between January 2011 and April 2017 at our institution. We identified patients with anemia, defined as serum hemoglobin levels less than 13 mg/dL in men and 12 mg/dL in women, measured within two weeks prior to surgery, and compared this group to a cohort of patients with normal preoperative hemoglobin. Perioperative outcomes analyzed included estimated blood loss (EBL), operative time, perioperative blood transfusions, failed postoperative extubation, intensive care unit (ICU) admission, postoperative complications, length of stay (LOS), and 30-day readmission. Outcomes were compared by univariable and multivariable analyses, with significance set at p < 0.05. RESULTS: We identified 263 patients undergoing HHR. The median age was 66 years and most patients were female (78%, n = 206). Seventy patients (27%) were anemic. In unadjusted analyses, anemia was significantly associated with failed postoperative extubation (7 vs. 2%, p = 0.03), ICU admission (13 vs. 5%, p = 0.03), postoperative blood transfusions (9 vs. 0%, p < 0.01), and postoperative complications (41 vs. 18%, p < 0.01). On adjusted multivariable analysis, anemia was associated with 2.6-fold greater odds of postoperative complications (OR 2.57; 95% CI 1.36-4.86; p < 0.01). CONCLUSIONS: In this study, anemia had a prevalence of 27% in patients undergoing primary HHR. Anemic patients had 2.6-fold greater odds of developing postoperative complications. Anemia is common in patients undergoing primary HHR and warrants consideration for treatment prior to elective repair.

Characterization of SPR994, an Orally Available Carbapenem, with Activity Comparable to Intravenously Administered Carbapenems.

Carbapenems are potent antibacterials with broad-spectrum activity. However, poor oral absorption generally confines this important drug class to in-hospital use by intravenous (IV) administration. The continued rise in drug resistant pathogens creates a need for alternative oral therapies with broad-spectrum activity. SPR994 is a novel formulation of the orally bioavailable pivoxil prodrug of SPR859 (tebipenem) and is being developed as the first oral carbapenem for treatment of complicated urinary tract infections (cUTIs) in adults. Herein, we describe characteristics beneficial to oral administration and compare the in vitro and in vivo activity of SPR859 or SPR994 with IV carbapenems.

The art and science of surgery: Do the data support the banning of surgical skull caps?

BACKGROUND: Recommendations of the Joint Commission discourage the use of surgical skull caps in favor of bouffant or helmet headwear; however, data supporting such recommendations are limited and have been questioned in recent studies, as well as by our departmental and hospital leadership. At the end of December 2015, surgical caps were removed from our institution with the theoretic goal of decreasing surgical site infections. We aimed to assess the impact of this intervention on surgical site infection occurrence at our institution. METHODS: Using our institutional American College of Surgeons National Surgical Quality Improvement Program General and Vascular procedure-targeted data, we identified patients undergoing any surgical procedure classified as clean or clean-contaminated during a 12-month period before and after implementation of the surgical headwear policy. Patients without complete 30-day follow-up were excluded. Cases with active infection at the time of operation were excluded. Vascular surgery operations were excluded because of the implementation of a separate intervention to decrease surgical site infections during the study period. Patients were grouped according to timing of the operation in relation to the policy change (12 months before or after). Descriptive statistics focused on proportions and adjusted logistic regression models were used to investigate the association of alternative headwear use with any type of surgical site infection. Models were adjusted for potential confounders that included demographics and clinical characteristics (age, sex, race or ethnicity, obesity, diabetes, steroid use, smoking status, cancer, urgency of the operation, and wound classification). RESULTS: A total of 1,901 patients underwent 1,950 procedures during the study period, with 767 (40%) before and 1,183 (60%) after the headwear policy measure was adopted. The most common procedures overall were colectomy (18%), pancreatectomy (13.5%), and ventral hernia repair (8.9%). The overall rate of any surgical site infection was 5.4%, with no difference before and after policy implementation (5.3% versus 5.5%; P = .81). Multivariate analysis controlling for age, sex, race or ethnicity, obesity, diabetes, smoking status, steroid use, cancer diagnosis, and type of wound classification showed no association between implementation of this new policy and surgical site infections occurrence (odds ratio 1.12 [95% confidence interval 0.73-1.71]; P = .59). CONCLUSION: In our institution, the strict implementation of bouffant or helmet headwear, with removal of skull caps from the operating room, was not associated with decreased surgical site infections for clean and clean-contaminated cases. Further evidence is required to assess the validity of this headwear guideline of the Joint Commission and support nationwide implementation of this policy.

Tebipenem, the first oral carbapenem antibiotic.

INTRODUCTION: Infections caused by antibiotic-resistant pathogens, particularly Gram-negative bacteria, have become increasingly challenging to successfully treat. The beta-lactam antibiotic subclass, the carbapenems, have proven valuable for the treatment of such Gram-negative bacterial infections due to their spectrum and ß-lactamase stability properties. However, all marketed carbapenems to date are parenterally administered to adult patients. Areas covered: One carbapenem, tebipenem-pivoxil (TBPM-PI), is an oral prodrug that was approved in Japan for pediatric use only in 2009. This review summarizes preclinical and clinical data for TBPM-PI, which is now in clinical development again this time for use as the first oral carbapenem available for treatment of bacterial infections in adult patients. Expert commentary: There is an urgent unmet need with an increasing prevalence of fluoroquinolone-resistant and ESBL-producing Gram-negative pathogens in the hospital and community setting. Carbapenems have traditionally been considered the drugs of choice for infections caused by enterobacteria producing ESBL and AmpC enzymes because they are not affected by these resistance mechanisms. The carbapenem, TBPM-PI, offers an oral option, particularly as step-down therapy, for use of this class in the treatment of serious Gram-negative infections.