The Timing of Limb Amputation in Nontraumatic Patients: Impact on Mortality and Postoperative Complication Rates.

Diabetes and peripheral vascular diseases are accompanied frequently by lower limb ischemia and in minority, need for amputation, as a treatment of last resort. Even after a decision has been made regarding amputation, the procedures are often repeatedly postponed due to more urgent surgeries and lack of operating room availability. This study assessed the possible relationship between the duration of time inpatients wait for semiurgent amputations and the incidence of postamputation complications. A retrospective cohort, including all 360 adult patients who underwent nontraumatic limb amputation due to an ischemic/gangrenous/infected foot in a single center during an 11-year period (2007-2017). Most (96%) of the procedures were major amputations. The mean waiting time until amputation was 3 ± 5 days. Mortality during hospitalization occurred in 101 (28%) patients and re-amputation in 38 (11%). The duration of antibiotic treatment was 11 ± 14 days. The rate of sepsis was 30% (107/360). There was no significant difference between the duration of time until amputation and mortality during hospitalization: among those who waited ≤48 hours, the mortality rate was 27% (60/224) and among those who waited >48 hours 30% (41/136) (p = .5). Patients waiting ≤48 hours had higher re-amputation rates than those waiting >48 (31/223 (14%) vs 7/136 (5%), p = .009). Mortality was associated significantly to patients' age and renal function. Correlation was found between the waiting time until amputation (≤48 or >48 hours) and the rates of in-hospital mortality, sepsis, duration of antibiotic treatment and overall duration of hospitalization. Re-amputation rate was higher in group with the shorter waiting time. This correlation may be explained by the fact that patients who needed urgent amputation had a more extensive and severe disease, and thus tended to require more re-amputation operations.

Identifying factors affecting latent tuberculosis treatment acceptance among healthcare workers: a retrospective analysis in a tertiary care centre.

OBJECTIVE: Official guidelines recommend tuberculosis (TB) screening programmes for all healthcare workers (HCWs), along with offering treatment when latent TB infection (LTBI) is diagnosed. However, adherence to treatment among HCWs is lower compared with non-HCWs. The aim of the present study was to examine the rate of LTBI treatment acceptance among HCWs and to characterise the factors associated with non-acceptance. DESIGN AND SETTING: This was a retrospective cohort study. All HCWs diagnosed with LTBI, who had tuberculin skin test (TST) conversion during their work, between 2000 and 2015, in a single tertiary academic medical centre, and who consented to answer a questionnaire, were enrolled. RESULTS: Overall, 147 of 219 (67%) with TST conversion agreed to participate. Acceptance rate for LTBI treatment was only 16%. The overall completion rate among those who accepted treatment was 87%. HCWs' recall of discussing the importance of LTBI treatment with their caregiver had the strongest association with LTBI treatment acceptance: 23 of 52 HCWs (44%) who recalled this discussion accepted treatment (adjusted OR=10.2, 95% CI: 2.2 to 47.6, p=0.003). Knowing the risk of developing TB was associated with 3.7 increased odds to accept treatment (95% CI: 1.2 to 11.8, p=0.02). CONCLUSIONS: LTBI acceptance rate was very low among our HCWs. Focusing on educating HCWs is potentially the key step towards an increased rate of LTBI treatment acceptance.

BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel.

OBJECTIVES: The mRNA coronavirus disease 2019 (COVID-19) vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease and death. Nevertheless, a minority of vaccinated individuals might become infected and experience significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination. METHODS: A retrospective multicentre cohort study of 17 hospitals included patients fully vaccinated with Pfizer/BioNTech's BNT162b2 vaccine who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed. RESULTS: A total of 152 patients were included, accounting for half of hospitalized fully vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notably, the cohort was characterized by a high rate of co-morbidities predisposing to severe COVID-19, including hypertension (108; 71%), diabetes (73; 48%), congestive heart failure (41; 27%), chronic kidney and lung diseases (37; 24% each), dementia (29; 19%) and cancer (36; 24%), and only six (4%) had no co-morbidities. Sixty (40%) of the patients were immunocompromised. Higher viral load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titres of anti-Spike IgG, but these differences did not reach statistical significance. CONCLUSIONS: We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully vaccinated individuals with multiple co-morbidities. Our patients had a higher rate of co-morbidities and immunosuppression compared with previously reported non-vaccinated hospitalized individuals with COVID-19. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social distancing, or by additional active or passive vaccinations.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome. METHODS: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys. RESULTS: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae. CONCLUSION: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

Diagnosis of Imported Monkeypox, Israel, 2018.

We report a case of monkeypox in a man who returned from Nigeria to Israel in 2018. Virus was detected in pustule swabs by transmission electron microscopy and PCR and confirmed by immunofluorescence assay, tissue culture, and ELISA. The West Africa monkeypox outbreak calls for increased awareness by public health authorities worldwide.

The risk of tuberculosis in cancer patients is greatest in lymphoma and myelodysplastic syndrome/myeloproliferative neoplasm: a large population-based cohort study.

Patients with cancer are at high risk for tuberculosis (TB). This study combined the Israeli databases of cancer and TB and examined the development of TB among all newly diagnosed cancer cases from 1993 to 2013. Patients were classified into groups according to their different malignancies. Among 495,335 cancer patients, 335 developed TB following cancer diagnosis. The cumulative incidence of TB following cancer diagnosis was highest among MDS/MPN (148.8/100,000 patients) and lymphoma (154.1/100,000 patients) (p = .023). The HR of TB following cancer among hematologic patients was 2.51 (p < .001), relative to patients with in situ carcinomas/skin cancer and highest among MDS/MPN and lymphoma patients (2.74, p = .012 and 2.70, p < .001, respectively). Among lymphoma patients, a significant increased HR was found only among NHL patients (2.72, p < .001). The limitations include lack of information regarding risk factors for TB and of anti-cancer treatments. In conclusion, these data may encourage a heightened awareness for TB among patients with a background of lymphoma and MDS/MPN.

Pneumococcal Meningitis in Adults after Introduction of PCV7 and PCV13, Israel, July 2009-June 20151.

The indirect effect of pneumococcal conjugate vaccine on adult pneumococcal meningitis has not been thoroughly investigated. We present data from active surveillance on pneumococcal meningitis in adults in Israel occurring during July 2009-June 2015. Pneumococcal meningitis was diagnosed for 221 patients, 9.4% of all invasive pneumococcal disease (IPD) cases. Although overall IPD incidence decreased during the study period, meningitis increased nonsignificantly from 0.66 to 0.85 cases/100,000 population. Incidence of vaccine type (VT) pneumococcal meningitis (VT13) decreased by 70%, but non-VT13 pneumococcal meningitis increased from 0.32 to 0.75 cases/100,000 population (incident rate ratio 2.35, 95% CI 1.27-4.35). Pneumococcal meningitis patients were younger and healthier than nonmeningitis IPD patients, and 20.2% had a history of previous head surgery or cerebrospinal fluid leak compared with <2.0% of nonmeningitis patients (p<0.0001). Non-VT13 types that rarely cause IPD (15B/C, 6C, 23A, 23B, 24F) seem to be emerging as common causes of meningitis.

Anesthesia in patients with infectious disease caused by multi-drug resistant bacteria.

PURPOSE OF REVIEW: Up to 50% of specific bacterial strains in healthcare admission facilities are multi-drug resistant organisms (MDROs). Involvement of anesthesiologists in management of patients carrying/at risk of carrying MDROs may decrease transmission in the Operating Room (OR). RECENT FINDINGS: Anesthesiologists, their work area and tools have all been implicated in MDRO outbreaks. Causes include contamination of external ventilation circuits and noncontribution of filters to prevention, inappropriate decontamination procedures for nondisposable equipment (e.g. laryngoscopes, bronchoscopes and stethoscopes) and the anesthesia workplace (e.g. external surfaces of cart and anesthesia machine, telephones and computer keyboards) during OR cleaning and lack of training in sterile drug management. SUMMARY: Discussions regarding the management of potential MDRO carriers must include anesthesia providers to optimize infection control interventions as well as the anesthesia method, the location of surgery and recovery and the details of patient transport. Anesthesia staff must learn to identify patients at risk for MDRO infection. Antibiotic prophylaxis, although not evidence based, should adhere to known best practices. Adjuvant therapies (e.g. intranasal Mupirocin and bathing with antiseptics) should be considered. Addition of nonmanual OR cleaning methods such as ultraviolet irradiation or gaseous decontamination is encouraged. Anesthesiologists must undergo formal training in sterile drug preparation and administration.

Urinary neutrophil gelatinase-associated lipocalin for early detection of acute kidney injury in geriatric patients with urinary tract infection treated by colistin.

INTRODUCTION: Colistin (polymyxin E) was developed ~ 60 years ago but was rarely used in clinical practice during the last 20 years because of concerns related to high rates of nephrotoxicity. However, it was recently reintroduced to clinical practice in many parts of the world for the treatment of multi-drug resistant gram-negative bacilli. In the current study, we evaluated the predictive capacity of urine neutrophil gelatinase-associated lipocalin (NGAL) for early diagnosis of acute kidney injury (AKI) in geriatric patients with urinary tract infection (UTI) receiving colistin therapy. METHODS: We studied 116 patients aged 80.7 ± 12 treated with colistin who suffered from UTI. Urinary NGAL was measured at baseline and 1 - 2 hours after the second dose of colistin. The primary outcome was AKI. Secondary outcome was in-hospital morbidity and mortality. RESULTS: 52 patients (44.8%) developed acute tubular necrosis (ATN) (14% of these had underlying CKD), 8 (7%) had prerenal azotemia, 8 (7%) had stable CKD without changes in renal function during hospitalization and the remaining 48 patients (41%) had normal kidney function. The mean duration of colistin therapy was 9.1 ± 4.8 days. At baseline, urine NGAL was 405 ± 452 g/l in ATN, 285 ± 256 g/l in prerenal azotemia, 390 ± 468 g/l in CKD and 347 ± 877 g/l in normal kidney function patients (difference non-significant). We were unable to demonstrate statistically significant increments of urine NGAL following colistin administration in either ATN or non-ATN patient groups. Urine NGAL was not correlated with urinary leukocyte or erythrocyte counts or baseline comorbidities such as CKD, heart failure, or diabetes. For primary outcome (ATN), receiver operating characteristics curve revealed AUC 0.59 (95% CI 0.49 - 0.7) sensitivity 0.65, and specificity 0.62 for a cutoff value of urinary NGAL 140 g/l. Similar results were obtained for secondary outcomes. CONCLUSIONS: Our data suggest limited predictive capacity of urinary NGAL for early diagnosis of AKI in a large clinical setting of geriatric patients hospitalized for UTI and receiving the potentially nephrotoxic colistin. This finding is likely due to the powerful influence of UTI on NGAL levels in both patients with normal kidney function and those with a wide spectrum of acute or chronic kidney diseases.

Antiphospholipid antibodies during infectious mononucleosis and their long term clinical significance.

BACKGROUND: The prevalence of antiphospholipid antibodies (aPLs) during acute Epstein-Barr virus (EBV) infection may be as high as 30-60%. The role of these autoantibodies in the development of antiphospholipid syndrome (APS) is not clear. OBJECTIVE: To investigate the prevalence, persistence and clinical significance of aPLs in a series of patients diagnosed with acute EBV infection. STUDY DESIGN: A cohort of 94 patients aged 15 or older, recently diagnosed with acute EBV was retrieved. Serum samples obtained during diagnosis were tested for the presence of aPLs and anti-ß2GP antibodies. Patients with positive sera for aPLs were assessed for the persistence of aPLs and the development of APS. RESULTS: The prevalence of aPLs among 94 patients with acute EBV was 37.2%. Five of 27 available serum samples were also positive for anti-ß2 glycoprotein (anti-ß2GP) antibodies. Repeat testing for aPLs after a median of 21 months post acute infection (range 13-50 months) was performed in 17 of the 35 patients with positive aPL test. All 17 patients were found negative for aPL-IgG antibodies. Two of them had positive aPL-IgM antibodies and positive anti-ß2GP antibodies. None of the patients who had positive aPLs experienced any manifestations of APS. CONCLUSION: The disappearance of aPLs in the majority of the patients after acute EBV infection, along with the absence of consistent clinical findings, suggests that the detection of aPLs during acute EBV is not associated with the development APS over time.

The cellular immunological responses of patients undergoing coronary artery bypass grafting compared with those of patients undergoing valve replacement.

OBJECTIVE: Major surgical intervention such as cardiac surgery has been shown to have profound effects on the immune system. We conducted a prospective study comparing the effects of coronary artery bypass grafting (CABG) versus isolated valve surgery. METHODS: Blood samples were drawn from 59 patients undergoing either elective CABG or elective isolated valve replacement surgery. Samples were obtained preoperatively and on the first and third postoperative days. Total cell counts and differential counts were recorded. Several cellular immunity parameters were determined by flow cytometry. RESULTS: On all postoperative days, significant increases in white blood cell (WBC) and monocyte counts were observed. Significant decreases in all lymphocyte populations were also observed with similar decreases in both helper (CD4) and suppressor (CD8) T cells. An increase in activated T cells was noted on day 1, returning to normal on the third postoperative day. Despite the significant decrease in human leucocyte antigen-DR (HLA-DR) antigen expression on monocytes on both the first and third postoperative days, a significant increase in monocyte activation as represented by increased CD11b and CD64 expression was detected. No significant difference was found for any of the measured parameters between the CABG group and the valve replacement group. Eight patients developed early wound infections, with no correlation with any of the measured parameters, including magnitude and duration of decrease in HLA-DR antigen expression on monocytes. CONCLUSIONS: Cardiac surgery induces both a state of pro-inflammation and of immune suppression. The two major types of cardiac surgery induce similar effects to the immune system. None of the measured parameters was predictive for development of postoperative wound infection.

Cefuroxime for empiric treatment of community-acquired pneumococcal pneumonia: is there a generation gap?

BACKGROUND: Streptococcus pneumoniae infection is an important cause of morbidity and mortality. The recommendations to use expanded-spectrum beta-lactam drugs for patients with community-acquired pneumonia derived from the growing prevalence of penicillin-resistant pneumococci. Controversy exists regarding the use of second generation cephalosporins for empirical treatment of community-acquired pneumonia. METHODS: In a retrospective study, 31 adult patients with pneumococcal pneumonia and bacteremia caused by S. pneumoniae that was intermediately resistant to penicillin were compared with 31 control patients with similar infection caused by penicillin-susceptible pneumococci. All patients were treated empirically with cefuroxime, alone or in combination with other antibiotics. Morbidity and mortality were studied. RESULTS: All unsusceptible pneumococci isolates were intermediately resistant to penicillin. No cases of fully resistant pneumococci were isolated from blood cultures in our hospital. Two factors were significantly associated with non-susceptibility to penicillin: hematologic malignancy and immunosuppression. No significant difference in morbidity or mortality was detected between the 2 groups, and penicillin minimum inhibitory concentration was not found to be a factor associated with mortality. CONCLUSIONS: Patients with pneumococcal pneumonia caused by intermediately resistant pneumococci can be empirically treated with cefuroxime. In regions where fully resistant pneumococci are rare, the use of a second generation cephalosporin for empiric treatment of community-acquired pneumonia may be appropriate.

Incidence and risk factors for surgical infection after total knee replacement.

Surgical site infection (SSI) after total knee replacement (TKR) is a devastating complication. We performed a retrospective study of all consecutive TKRs performed during a 2-y period. Surgical site infection (SSI) was defined by standard criteria. All patients were examined 1 y following surgery. Of 180 patients undergoing TKR, 10 (5.6%) developed a superficial (3, 1.7%) or deep (7, 3.9%) SSI. Two independent risk factors for SSI were detected: left knees became infected more often (9/ 92, 9.8%) than right knees (1/88, 1.1%) (Relative Risk 6.7 +/- 95% CI 1.7-26.8); and 7/72 (9.7%) patients receiving a type-1 prosthesis developed infection versus 3/104 (3.1%) receiving a type-2 prosthesis (RR 4.7, 95% CI 1.18-18.4). Investigation of the operating room revealed 3 problems: there was significant traffic through the door on the left of the patient; a nonstandard horizontal-flow air conditioner had been installed above that door; a tool-washing sink was in use on the other side of that door. Infection control guidelines were rehearsed: the sink was removed, the air conditioner was disconnected, and the door was locked. In a prospective survey performed 2 y later only 1/45 patients (2.2%) undergoing TKR developed a superficial SSI (p = 0.5). Correction of independent risk factors for infection following TKR led to a decrease in SSI rate.