Identifying Vancomycin as an Effective Antibiotic for Killing Borrelia burgdorferi.

Borrelia burgdorferi is the causative agent of Lyme borreliosis. Antibiotic therapy of early acute infection is effective for most patients, but 10 to 20% go on to develop posttreatment Lyme disease syndrome (PTLDS). The nature of PTLDS remains unknown, but currently approved antibiotics for the treatment of Lyme disease do not appear to impact these symptoms after they have developed. We reason that minimizing the time the pathogen interacts with the host will diminish the probability of developing PTLDS, irrespective of its nature. This calls for an efficient eradication of the pathogen during acute infection. In search of a superior killing antibiotic, we examined approved antibiotics for their ability to kill B. burgdorferi Vancomycin proved more effective in killing the pathogen in vitro than ceftriaxone, the standard of care for disseminated B. burgdorferi infection. Both compounds were also the most effective in killing stationary-phase cells. This is surprising, given that inhibitors of cell wall biosynthesis are known to only kill growing bacteria. We found that peptidoglycan synthesis continues in stationary-phase cells of B. burgdorferi, explaining this paradox. A combination of vancomycin and gemifloxacin sterilized a stationary-phase culture of B. burgdorferi Examination of the action of antibiotics in severe combined immunodeficient (SCID) mice showed that doxycycline, a standard of care for uncomplicated acute infection, did not clear the pathogen. In contrast, both ceftriaxone and vancomycin cleared the infection. A trial examining the early use of more potent antibiotics on the development of PTLDS may be warranted.

Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells.

Borrelia burgdorferi is the causative agent of Lyme disease, which affects an estimated 300,000 people annually in the United States. When treated early, the disease usually resolves, but when left untreated, it can result in symptoms such as arthritis and encephalopathy. Treatment of the late-stage disease may require multiple courses of antibiotic therapy. Given that antibiotic resistance has not been observed for B. burgdorferi, the reason for the recalcitrance of late-stage disease to antibiotics is unclear. In other chronic infections, the presence of drug-tolerant persisters has been linked to recalcitrance of the disease. In this study, we examined the ability of B. burgdorferi to form persisters. Killing growing cultures of B. burgdorferi with antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants. The level of persisters increased sharply as the culture transitioned from the exponential to stationary phase. Combinations of antibiotics did not improve killing. Daptomycin, a membrane-active bactericidal antibiotic, killed stationary-phase cells but not persisters. Mitomycin C, an anticancer agent that forms adducts with DNA, killed persisters and eradicated growing and stationary cultures of B. burgdorferi. Finally, we examined the ability of pulse dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and the antibiotic was added again. Four pulse doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture.

Demographics and Outcomes of Interhospital Transfer Patients Undergoing Intracranial Tumor Resection: A Retrospective Cohort Analysis.

Introduction Interhospital transfer (IHT) contributes to increasing health care costs and typically accounts for increased patient morbidity and mortality compared to non-IHT patients. IHT inefficiencies leave patients vulnerable to delayed care and subsequent poor outcomes. In this study, we investigated factors influencing IHT of patients undergoing intracranial tumor resection (ITR), by comparing the variables distinguishing IHTs from non-IHT patients. Methods We performed a single-center retrospective review comparing IHT and non-IHT patients undergoing ITR from 2016 to 2018. Study variables included age, sex, race, the Milan Complexity Scale (MCS) score, 11-factor modified frailty index (mFI-11), length of stay (LOS), and Clavien-Dindo Score (CDS). Chi-square and Mann-Whitney U tests were used to identify significant differences in these variables between groups, while variables predictive of transfer status were identified using binary logistic regression. Results Data were collected from 219 patients undergoing ITR, with 80 (36.5%) IHT patients overall. The average age was 52 years (SD 18) and 57.7% were men. The MCS score was significantly higher in the IHT group (p = 0.014); however, mFI-11 was not (p = 0.322). The MCS score was predictive of IHT status in regression analysis (OR 1.17, p = 0.034). The IHT patients had a longer LOS (12 days vs 8 days, p = 0.014) with a lower CDS (p = 0.02). Conclusion The transfer patients for intracranial tumor resection had a higher MCS score and thus comprised a more surgically challenging population compared to non-transfer patients. As expected, IHT patients had a longer LOS as they lived further from hospital by definition.

Spine surgery complexity score predicts outcomes in 671 consecutive spine surgery patients.

BACKGROUND: The spine surgery complexity score (SSCS), previously reported by us, is a simple grading system to predict postoperative complications and hospital length of stay (LOS). This scale is based on the technical difficulty of the spinal procedures being performed. METHODS: We performed a retrospective chart review to validate SSCS in 671 consecutive patients undergoing spine procedures at a quaternary academic hospital. RESULTS: The SSCS was predictive of the hospital LOS and postoperative complications (defined by the ClavienDindo score), based on linear regression analysis (P < 0.001 for both). CONCLUSION: Categorizing procedures according to the SSCS may enable neurosurgeons to assess surgical risk and predict longer LOS courses after spine surgery. Thus, it may prove useful in preoperative patient evaluation/ education and determining a prognosis based on surgical complexity.

Neurocritical care management of poor-grade subarachnoid hemorrhage: Unjustified nihilism to reasonable optimism.

BACKGROUND AND PURPOSE: Historically, overall outcomes for patients with high-grade subarachnoid hemorrhage (SAH) have been poor. Generally, between physicians, either reluctance to treat, or selectivity in treating such patients has been the paradigm. Recent studies have shown that early and aggressive care leads to significant improvement in survival rates and favorable outcomes of grade V SAH patients. With advancements in both neurocritical care and end-of-life care, non-treatment or selective treatment of grade V SAH patients is rarely justified. Current paradigm shifts towards early and aggressive care in such cases may lead to improved outcomes for many more patients. MATERIALS AND METHODS: We performed a detailed review of the current literature regarding neurointensive management strategies in high-grade SAH, discussing multiple aspects. We discussed the neurointensive care management protocols for grade V SAH patients. RESULTS: Acutely, intracranial pressure control is of utmost importance with external ventricular drain placement, sedation, optimization of cerebral perfusion pressure, osmotherapy and hyperventilation, as well as cardiopulmonary support through management of hypotension and hypertension. CONCLUSIONS: Advancements of care in SAH patients make it unethical to deny treatment to poor Hunt and Hess grade patients. Early and aggressive treatment results in a significant improvement in survival rate and favorable outcome in such patients.

Demographics and Outcomes of Interhospital Neurosurgical Transfer Patients Undergoing Spine Surgery.

OBJECTIVE: Interhospital patient transfer (IHT) of patients is common and accounts for a significant portion of health care costs, yet the variables driving neurosurgical IHT have not been systematically described. We analyzed variables that distinguished spine surgery patients who underwent IHT from patients who did not undergo IHT to report on the effect of frailty on IHT. METHODS: A retrospective chart review was performed to collect data on consecutive patients undergoing spinal procedures during 2015-2017. IHT patients were identified and compared with non-interhospital patient transfer (n-IHT) patients to identify factors that distinguished the 2 patient groups using multivariate regression analysis. Studied variables included case complexity, frailty (modified frailty index), age, insurance status, and baseline demographic variables. Postoperative outcomes affected by transfer status were identified in binary regression analysis. RESULTS: During 2015-2017, there were 595 n-IHT and 76 IHT spine surgery patients (N = 671). Increased frailty (modified frailty index ≥3; odds ratio = 2.4, P = 0.01) and increased spine surgery complexity (spine surgery complexity score ≥2; odds ratio = 2.57, P = 0.002) were independent risk factors associated with IHT. IHT was an independent risk factor for increased hospital length of stay and increased postoperative complications (Clavien-Dindo scale; P < 0.001). CONCLUSIONS: IHT patients comprise a more frail and surgically complex surgical spine population compared with n-IHT patients. IHT was also an independent risk factor for increased complications and length of stay after spine surgery. Patients' insurance status and age did not distinguish between IHT and n-IHT groups. This is the first report in any specialty to demonstrate increasing frailty is associated with IHT.