Urinary tract infections in hemodialysis patients-The controversy of antimicrobial drug urine concentrations.

BACKGROUND: Major infectious diseases societies recommend the use of antimicrobials that achieve high-urinary concentrations to treat urinary tract infection (UTI), which is a concept of little relevance to the oliguric and anuric hemodialysis (HD) dependent population. Outcome studies in this population are more relevant, but unfortunately scarce. We sought to investigate the impact of different antimicrobials on clinical and microbiologic outcomes in HD dependent population. METHODS: A retrospective observational study conducted at our quaternary care hospital between May 2015 and December 2019. We included all HD dependent adults diagnosed with UTIs. Our primary end points were clinical and microbiologic cure. Our secondary end points were 90-day recurrence and mortality. RESULTS: Fifty-six patients were included in the study with 33 (58.9%) females, mean age of 69.9 ± 11.6 years, and mean body mass index of 27.7 ± 7.8 kg/m2 . Thirty-six subjects of the sample (64.3%) were anuric. Ninety-one percent of the patients achieved clinical cure. Out of those who had repeat cultures, 90.7% achieved microbiologic cure. Clinical and microbiologic cure rates were not significantly different between the oliguric and anuric groups. The 90-day recurrence rate was 11.1% and mortality was 19%, none of them was related to UTI. CONCLUSION: Our findings demonstrate high rate of clinical and microbiologic cure in the treatment of oliguric and anuric HD dependent patients. We suggest that drug development and treatment societies to consider clinical and microbiologic outcomes in conjunction with achievable urinary concentration when making recommendations for the treatment of UTI.

Nocardial Infection in the Early Period after Kidney Transplantation.

Patients with solid organ transplant have weaker immune system and can develop opportunistic infections. Prophylactic antimicrobials can help lower that risk but do not prevent it completely. High index of suspicion increases the chance of diagnosing rare opportunistic infections in immunocompromised patients and helps early and effective treatment. We present a unique case of a patient who developed pneumonia from Nocardia early after kidney transplant despite being on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. He was diagnosed and treated early which helped improving his outcome. We discuss incidence, risk factors, and treatment of nocardiosis post kidney transplant.

Is Cefoxitin a Carbapenem Sparing Agent in the Management of Urinary Tract Infections Caused by ESBL Producing Enterobacterales?

Background: Cefoxitin has shown in vitro activity against Extended-Spectrum ß-Lactamase (ESBL) producing Enterobacterales. Outcome data regarding cefoxitin as a carbapenem sparing agent in the management of urinary tract infections (UTI) are scarce. We sought to evaluate the clinical and microbiologic efficacy of cefoxitin as compared to ertapenem. Methods: A retrospective observational study was conducted at our quaternary care institution between May 2015 and March 2019. We identified all patients who received cefoxitin for the treatment of UTI during the study period and used Charlson Comorbidity Index to select a matching cohort from patients who received ertapenem. Primary end points were clinical and microbiological cure. Results: Thirty patients who received cefoxitin were matched with 55 patients who received ertapenem. Clinical cure was marginally in favor of ertapenem: 83.2% in cefoxitin group versus 96.8% in ertapenem group (P = .042). However, 90-day recurrence was in favor of cefoxitin: 13.5% in cefoxitin group versus 34.8% in ertapenem group (P = .045). Microbiologic cure was not significant between the 2 groups with 88.6% success in cefoxitin versus 100% in ertapenem. Additionally, the group difference on 30-day recurrence or relapse rates and the 90-day mortality rate were not clinically significant. Conclusion: Cefoxitin achieved similar microbiologic cure rate when compared to ertapenem for the treatment of UTI caused by ESBL-producing Enterobacterales. No significant differences were found in 30-day recurrence/relapse or mortality rates. Larger randomized controlled trials are required to identify the clinical sittings in which cefoxitin could be used as a carbapenem-sparing agent in the treatment of UTI.

Outcomes of caspofungin use in the treatment of Candida-related urinary tract infections, a case series.

Echinocandins are generally excluded in the treatment of Candida-related urinary tract infections due to their poor urinary concentration. In the presence of fluconazole resistant Candida species, such as C. Glabrata and C. auris, alternative therapies are needed. We herein report the use of caspofungin for the treatment of 10 patients with candiduria, including C. auris. Mycological cure was achieved in 6 of 7 patients and clinical cure was achieved in 8 of 10 patients. Larger studies are needed to confirm our findings.

Multiple concomitant life-threatening opportunistic infections due to uncontrolled hypercortisolism.

Opportunistic infections associated with severe cortisol excess carry a high mortality rate and are most prevalent with ectopic ACTH syndrome. There are limited reports of these cases described in the literature. In this case report, we describe multiple severe life-threatening opportunistic infections due to endogenous hypercortisolism. Our patient, against numerous expectations, survived multiple opportunistic infections including disseminated invasive aspergillosis, Cytomegalovirus endophthalmitis and Pneumocystis Jirovecii pneumonia, reinforcing the need for multidisciplinary care for patients presenting with complicated hypercortisolism.

Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study.

(1) Background: There are limited data regarding the efficacy of convalescent plasma (CP) in critically ill patients admitted to the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). We aimed to determine whether CP is associated with better clinical outcome among these patients. (2) Methods: A retrospective single-center study including adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to the ICU for acute respiratory failure. The primary outcome was time to clinical improvement, within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale. (3) Results: Overall, 110 COVID-19 patients were admitted. Thirty-two patients (29%) received CP; among them, 62.5% received at least one CP with high neutralizing antibody titers (≥1:160). Clinical improvement occurred within 28 days in 14 patients (43.7%) of the CP group vs. 48 patients (61.5%) in the non-CP group (hazard ratio (HR): 0.75 (95% CI: 0.41-1.37), p = 0.35). After adjusting for potential confounding factors, CP was not independently associated with time to clinical improvement (HR: 0.53 (95% CI: 0.23-1.22), p = 0.14). Additionally, the average treatment effects of CP, calculated using the inverse probability weights (IPW), was not associated with the primary outcome (-0.14 days (95% CI: -3.19-2.91 days), p = 0.93). Hospital mortality did not differ between CP and non-CP groups (31.2% vs. 19.2%, p = 0.17, respectively). Comparing CP with high neutralizing antibody titers to the other group yielded the same findings. (4) Conclusions: In this study of life-threatening COVID-19 patients, CP was not associated with time to clinical improvement within 28 days, or hospital mortality.

Residency training in the time of COVID-19: A framework for academic medical centers dealing with the pandemic.

BACKGROUND: As cases of COVID-19 climb worldwide, academic medical centers (AMCs) are scrambling to balance the increasing demand for medical services while maintaining safe learning environments. The scale and nature of the current pandemic, limitations on key resources, risks of transmission, and the impact on trainee wellbeing pose additional challenges to AMCs. We propose a framework for AMCs to utilize in facilitating health system, organization and program-level adjustments to meet the needs of medical trainees during the pandemic. APPROACH: In February 2020, we developed a three-level approach to the pandemic response of training programs at our AMC. The first level involved AMC alignment and engagement with regulatory stakeholders. The second level utilized the graduate medical education committee and leveraged organizational functions such as human resources, finance, and clinical departments. The third level of intervention focused on common approaches used by programs to ensure continuity of learning in the context of dynamic changes in workflows and service operations. EVALUATION: Outcomes at each level are reported. These include the co-development of a national framework on medical trainee responses to COVID-19, the composition of an operational guidance document, organizational protocols to accommodate novel challenges posed by the pandemic, and multiple program-level interventions. REFLECTION: This methodical approach, employed during a global crisis, was critical in facilitating interventions required to fulfill the mission of AMCs. Future steps include assessing the impact of these changes on trainee performance and the applicability of the approach in diverse settings.

Ertapenem Neurotoxicity in Hemodialysis Patients-Safe and Effective Dosing Is Still Needed: A Retrospective Study and Literature Review.

BACKGROUND: The approved dosing of ertapenem in patients with chronic kidney disease stage 5 utilizing dialysis (CKD-5D) is 0.5 g intravenous daily. Several reports associated this dosing strategy with neurotoxicity. OBJECTIVE: The purpose of this study is to identify the incidence of neurotoxicity in this population and the risk factors associated with this toxicity. The secondary objective was to review the literature and discuss a safer/cost-effective dosing strategy based on available data. METHODS: A retrospective study was conducted screening all patients who received ertapenem and hemodialysis at our quaternary hospital between May 2015 and March 2019. Patients' demographics, comorbidities, concomitant drugs (known to induce neurotoxicity), and seizure history were collected. RESULTS: A total of 99 eligible patients were identified; 10 of them (10%) developed neurotoxicity. The patients who developed neurotoxicity were all male; mean age was 74 ± 9 years as compared with 68.9 ± 13 years in the sample. Bivariate relationships between all predictors and the seizures (dichotomously coded) were estimated to investigate the risk factors. The following were the significant predictors of seizures: male sex (17%; P = 0.014), dementia (27%; P = 0.012), and concomitant use of ß-lactams, aminoglycosides, or fluoroquinolones (19.6%; P = 0.042). CONCLUSION AND RELEVANCE: The currently approved ertapenem dose imposes a risk of developing neurotoxicity in patients with CKD-5D. Utilizing the published data in this population, alternative post-dialysis dosing strategies administered through dialysis access such as 1 g loading dose, followed by either 0.5 g (for the 48 hours interdialytic time) or 1 g (for the 72 hours interdialytic time) might warrant further investigation for efficacy and safety.

Comprehensive Approach to Reduce Surgical Site Infections in Patients Undergoing Neurosurgical Procedures.

Background: Surgical site infections (SSIs) are recognized complications of surgical procedures. Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the likelihood of developing SSIs. Decolonization of MRSA has been shown to reduce post-operative SSIs, therefore, the aim of this project was to identify and decolonize MRSA carriers and to tailor perioperative antibiotic prophylaxis to protect those at high risk for SSIs better. Methods: In September 2013, a quality improvement process initiative was implemented for pre-operative screening of MRSA nasal carriage for patients undergoing elective neurosurgical procedures. Those identified as colonized received a 10-day decolonization protocol that consisted of: oral doxycycline 100 mg twice daily or oral trimethoprim-sulfamethoxazole (TMP-SMX) DS twice daily; oral rifampin 600 mg daily; daily bathing with chlorhexidine; and twice daily use of mupirocin ointment in each nostril and under the fingernails. In addition to cefazolin (weight-based dosing), vancomycin (weight-based dosing) was recommended for perioperative prophylaxis in known MRSA carriers and patients undergoing surgical procedures involving hardware implantation irrespective of colonization status. We compared the results with our previously documented neurosurgical site infection rates (2012 and 2013 were 3.0 and 2.2%, respectively) Results: From 2014 to 2015, MRSA screening was done for 1,197 patients, of whom 52 (4.3%) were found to be colonized. Surgical site infections occurred in 14 procedures (1.4%) in 2014 and eight (0.8%) procedures in 2015, respectively. Methicillin-resistant Staphylococcus aureus remained responsible for most of these infections. None of the patients who underwent decolonization developed an infection (MRSA or otherwise). Conclusions: The overall rate of neurosurgical site infections can be reduced through a bundled approach of MRSA decolonization and change in perioperative antibiotic prophylaxis to include vancomycin for procedures involving hardware implantation irrespective of MRSA carriage state.

Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease.

ABSTRACT: There are conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patients. The objective of this study was to assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearance.Hospitalized adult patients with confirmed SARS-CoV-2 infection were retrospectively included in the study. The primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by 2 negative results using RT-PCR assay with samples obtained 24 hours apart. Multiple linear regression analysis was used to adjust for potential confounders.Thirty-four confirmed COVID-19 patients completed the study. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ than those who did not receive HCQ [17 (13-21) vs 10 (4-13) days, P = .023]. HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, comorbidities, antiviral drugs, pneumonia, or oxygen therapy) in multivariable Cox proportional hazards regression analysis (hazard ratio = 0.33, 95% confidence interval: 0.13-0.9, P = .024). On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared with 90.9% (10/11) patients who did not receive HCQ (P = .016).HCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.

Meningitis as the initial manifestation of systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is an idiopathic chronic autoimmune disease that can affect multiple organs including the Central Nervous System (CNS). CNS involvement is seen in many SLE patients; however, usually it is preceded by/or in conjunction with other organ-system involvement. The spectrum of CNS involvement is wide and includes numerous neuro-psychiatric syndromes but rarely meningitis. Even when meningitis occurs it is almost never the presenting manifestation of SLE. Our case had chronic aseptic meningitis as the initial and seemingly sole manifestation of SLE, which was erroneously, treated as tuberculous (TB) meningitis.

Persistent candidemia despite appropriate fungal therapy: First case of Candida auris from the United Arab Emirates.

In this case, we report an elderly patient with multiple chronic conditions and prolonged intensive care unit (ICU) stays who had recurrent Candida auris (C. auris) in blood despite antifungal therapy. C. auris was misidentified using conventional automated identification system as Candida haemulonii resulting in delayed diagnosis. The isolate showed increasing minimum inhibitory concentrations (MICs) to different antifungal drugs and persisted in the patient's blood before the patient deceased. This is the first case of C. auris reported from the United Arab Emirates (UAE); laboratories should be aware of this Candida species and should confirm suspected cases since it is an emerging multi-drug resistant and health-care associated Candida.

Comparison of antimicrobial activity between ceftolozane-tazobactam and ceftazidime-avibactam against multidrug-resistant isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

OBJECTIVE: This study compared the activity of ceftolozane-tazobactam and ceftazidime-avibactam against 120 bacterial strains, including extended-spectrum beta-lactamase (ESBL) producers, carbapenem-resistant Enterobacteriaceae (CRE), and Pseudomonas aeruginosa, isolated from patients admitted to Cleveland Clinic Abu Dhabi, United Arab Emirates. METHODS: In vitro susceptibility was tested using the Etest strip minimum inhibitory concentration (MIC) method, and PCR was used to characterize the carbapenemase enzymes produced by CRE strains. RESULTS: All 29 ESBL isolates were susceptible to ceftazidime-avibactam (MIC50 0.125µg/ml), whereas all but one were susceptible to ceftolozane-tazobactam (MIC50 0.38µg/ml). Twenty-seven (45%) CRE isolates were susceptible to ceftazidime-avibactam (MIC50 ≥256µg/ml), whereas only six (10%) isolates were susceptible to ceftolozane-tazobactam (MIC50 ≥256µg/ml). Very few NDM-1 isolates were susceptible to ceftazidime-avibactam, whereas the majority of OXA-48 isolates were susceptible. Twenty-nine (94%) P. aeruginosa isolates were susceptible to ceftazidime-avibactam (MIC50 1.5µg/ml), whereas 30 (97%) isolates were susceptible to ceftolozane-tazobactam (MIC50 0.75µg/ml). CONCLUSIONS: Ceftolozane-tazobactam and ceftazidime-avibactam showed comparable activity against ESBL and P. aeruginosa, with ceftazidime-avibactam having lower MICs against ESBL isolates and ceftolozane-tazobactam having lower MICs against P. aeruginosa. Ceftazidime-avibactam showed better activity against all CRE isolates except for those carrying the NDM-1 enzyme.

Systemic Air Embolism Associated with Pleural Pigtail Chest Tube Insertion.

Pleural pigtail catheter placement is associated with many complications including pneumothorax, hemorrhage, and chest pain. Air embolism is a known but rare complication of pleural pigtail catheter insertion and has a high risk of occurrence with positive pressure ventilation. In this case report, we present a 50-year-old male with bilateral pneumonia who developed a pneumothorax while on mechanical ventilation with continuous positive airway pressure mode. During the placement of the pleural pigtail catheter to correct the pneumothorax, the patient developed a sudden left sided body weakness and became unresponsive. An air embolism was identified in the right main cerebral artery, which was fatal.

Fatal pulmonary toxicity due to carfilzomib (Kyprolis™).

INTRODUCTION: Carfilzomib (Kyprolis™) is a second-generation proteasome inhibitor for the treatment of relapsing multiple myeloma (MM). In 2012, carfilzomib was approved by Food and Drug Administration for the treatment of patients with relapsed MM who had received at least two prior therapies. We present a case of fatal pulmonary toxicity presumed secondary to carfilzomib. CLINICAL PRESENTATION: A 61-year-old male was initially diagnosed with MM in 2003 for which he received multiple treatments. In 2013, he was started on carfilzomib for relapsing MM. After 24 h, the patient developed an acute respiratory distress syndrome for which he needed mechanical ventilation. One week later, patient developed diffuse alveolar hemorrhage and despite aggressive supportive care, the patient died after three weeks. DISCUSSION: The temporal relationship between the first exposure to carfilzomib and development of symptoms, and the exclusion of other possible etiologies, leads us to believe that our patient's lung toxicity is a possible adverse reaction to carfilzomib. To the best of our knowledge, there are no previous reports of deaths due to carfilzomib-related pulmonary toxicity.

Apparent lisinopril overdose requiring hemodialysis.

PURPOSE: A case of apparent overdose of angiotensin-converting-enzyme inhibitors requiring hemodialysis is reported. SUMMARY: A 51-year-old white man (weight, 85 kg; height, 178 cm; body mass index, 28) with a history of hypertension, low back pain, and anxiety apparently took 27 lisinopril 10-mg tablets (3.18 mg/kg body weight) over a period of 3 or fewer days. The friend who brought him to the emergency department reported that the patient was hard to rouse and was speaking incoherently on the day of admission. Over the previous few days, the patient reportedly had visual hallucinations, incoherence, and inarticulate speech. Laboratory tests, electrocardiography, and computed tomography were performed. The patient was judged to have high-anion-gap metabolic acidosis, acute kidney injury, severe hyperkalemia, and rhabdomyolysis. He was given three doses of albuterol via a nebulizer, three doses of calcium gluconate 1 g i.v., two doses of sodium bicarbonate 100 meq i.v., two doses of sodium polystyrene sulfonate 30 g orally, three doses of insulin 10 units i.v., and three doses of dextrose 25 g (as 50% dextrose injection) i.v. He then underwent emergent hemodialysis and was admitted to the intensive care unit. The patient's confusion abated, kidney function improved, and acid-base and electrolyte imbalances resolved. The patient was discharged after 15 days. CONCLUSION: A man who had evidently taken an overdose of lisinopril had multiorgan dysfunction in the absence of hypotension. The abnormalities resolved after he was treated for acidosis and hyperkalemia and received hemodialysis to remove the lisinopril.

Infection control experience in a cooperative care center for transplant patients.

OBJECTIVE: To characterize infection control experience during a 6.5-year period in a cooperative care center for transplant patients. DESIGN: Descriptive analysis. SETTING: A cooperative care center for transplanted patients, in which patients and care partners are housed in a homelike environment, and care partners assume responsibility for patient care duties. PATIENTS: Nine hundred ninety one transplant patients. METHODS: Infection control definitions from the Centers for Disease Control and Prevention were used to ascertain infection rates. Environmental cultures were used to detect methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Clostridium difficile, and fungi during the first 18 months. Surveillance cultures were performed for a subset of patients and care partners. RESULTS: From June 1999 through December 2005, there were 19,365 patient-days observed. The most common healthcare-associated infection encountered was intravascular catheter-related bloodstream infection, with infection rates of 5.74 and 4.94 cases per 1,000 patient-days for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) patients, respectively. C. difficile-associated diarrhea was observed more frequently in HSCT patients than in SOT patients (3.97 vs 0.57 cases per 1,000 patient-days; P < .0001). There was no evidence of environmental contamination with MRSA, VRE, or C. difficile. Acquisition of MRSA was not observed. Acquisition of VRE was documented. CONCLUSION: This study documented that cooperative care was associated with some risk of healthcare-associated infection, most notably intravascular catheter-associated bloodstream infection and C. difficile-associated diarrhea, it appears the incidences of these infections were roughly commensurate with those in other care settings.