Ten years with colistin: a retrospective case series.

OBJECTIVE: At the Shaare Zedek Medical Center, we have been using colistimethate sodium (CMS) for empiric as well as pathogen-directed treatment. We present our 10-year experience. METHODS: We conducted a retrospective case-series analysis of patients admitted from 1 January 2004 through 1 May 2014 who received at least one dose of CMS. Patient characteristics analysed for all admission for which patients received CMS, included: age, number of re-admissions, admission ward, renal function, disposition and microbiology results. Overall trend in defined daily dose (DDD) for CMS and resistant isolates was analysed. RESULTS: A total of 5603 admissions met inclusion criteria. Patients' mean (±SD) age was 80 ± 14 years, 1162 (48%) of the admissions were from a healthcare facility and 4367 (78%) of the admissions were to general Internal Medicine wards. The median number of hospital admissions per patient was 5, median admission and discharge creatinine (mg/dl) were 1.05 and 1.01, respectively; 2.3% of admissions required first-time dialysis. The discharge rate from the hospital was 58.4%. Excluding intrinsically CMS-resistant gram-negative organisms, bloodstream and urine isolates were 98% and 100% susceptible, respectively. CMS use (DDDs) increased during the study (p for trend = 0.04) without significant increase in incidence of multidrug-resistant organisms. CONCLUSIONS: Colistimethate sodium use at our institution has increased during this 10-year period. Nevertheless, there is no increasing trend in CMS-resistant organisms, 58% of the patients were discharged alive, and we did not observe significant nephrotoxicity in patients prescribed CMS. CMS should be reserved for microbiologically confirmed extensively drug-resistant gram-negative infections.

Faecal microbiota transplantation for Clostridium difficile infection.

PURPOSE: To review the current clinical literature regarding the use of fecal microbiota transplantation (FMT) for severe and recurrent Clostridium difficile disease (CDAD). BACKGROUND: Clostridium difficile (C. difficile) is a gram positive, spore forming bacteria, and an important nosocomial pathogen causing healthcare associated diarrhoea in hospitalized patients in developed and developing countries. During the past several years, CDAD has become more frequent, severe, refractory, and more likely to relapse. It has become apparent that C. difficile is no longer just a nosocomial infection, with a rising rate of infection in populations not previously affected. Standard treatment regimens and new medications exist, but recurrence rates are high. METHODS: Using PubMed, we conducted a Boolean search with the following medical subject headings (MeSH): Clostridium difficile infection and fecal transplantation or recurrent C. difficile infection. We restricted the search to human studies, published in English, between 2011 through June 1, 2013. RESULTS: There were 104 publications identified. Of those related to FMT, there were 20 clinical reviews, 6 case reports, 3 clinical trials (one, a randomized control trial), and 1 meta-analysis. Since 1958 there have been 36 published reports of FMT for C. difficile infection (CDI) representing 583 patients. Success rates were higher when FMT was administered via colonoscopy (representing the majority of patients, 79.2%). The overall success rate for FMT, regardless of administration method, was 80-98%. CONCLUSION: Fecal microbiota transplantation attempts to restore the normal microbiome of the colon, and has achieved a cure rate reaching more than 90%. Mounting evidence supports the utility of FMT for severe and recurrent cases of CDI. Barriers that will need to be addressed are patient perceptions and fears, standard protocol development, and further clinical trials.

Clinical characteristics and outcomes of diabetic patients with Staphylococcus aureus bacteremia and endocarditis.

The complications from S. aureus bacteremia (SAB) and infective endocarditis (SAIE) are higher in patients with diabetes. We summarize the characteristics and outcome of diabetic patients enrolled in a multicenter trial of daptomycin vs. standard therapy for SAB and SAIE. Adult patients with SAB were randomized to daptomycin 6 mg/kg/day or standard therapy (vancomycin 1 g every 12 h or antistaphylococcal penicillin 2 g every 4 h, both with gentamicin 1 mg/kg every 8 h for 4 days). Clinical success was defined as survival, resolution of S. aureus infection, and clinical outcome of cure or improved 6 weeks after end of therapy. Diabetic patients (86/235) were older, more overweight, and were more likely to present with systemic inflammatory response syndrome (SIRS) and to have complicated SAB. Clinical success rates were similar (67.4% in diabetics and 70.5% in non-diabetics). The mortality rate was significantly higher among diabetic patients (22.1% vs. 11.4%, p = 0.038). In the diabetes subgroup, the clinical success and mortality rates were comparable between the daptomycin and the standard therapy arms. The presence of diabetes is associated with significantly higher mortality in patients with SAB and SAIE. Daptomycin is an alternative therapeutic option in diabetic patients with these serious staphylococcal infections.

Outpatient parenteral antibiotic therapy with daptomycin: insights from a patient registry.

AIM: To compare and contrast the characteristics and clinical outcomes of patients who have received daptomycin as outpatients and inpatients. METHODS: The Cubicin Outcomes Registry and Experience (CORE) is a retrospective chart review of patients who have received daptomycin in participating institutions. Patients treated in 2005 were included in this analysis. Demographic characteristics and clinical outcomes (success = cured + improved) were compared among patients who received outpatient parenteral antibiotic therapy (OPAT) and patients who had received inpatient parenteral antibiotic therapy (IPAT). RESULTS: Of 1172 patients reported by 52 CORE 2005 participating institutions/investigators, 949 (81.0%) patients were evaluable: 539 (56.8%) received OPAT (OPAT patients), and 410 (43.2%) received only IPAT (IPAT patients). Of the 539 OPAT patients, 273 (50.6%) also received some IPAT, usually preceding OPAT therapy. Successful outcomes [no. of successes/(no. of successes + no. of failures)] for OPAT patients vs. IPAT patients were 94.6% and 86.3% respectively (chi-square test, p < 0.001). OPAT patients were younger, had fewer underlying diseases, were clinically stable, and had fewer adverse events than IPAT patients. CONCLUSIONS: Outpatient parenteral antibiotic therapy use was common (539/949 or 56.8%) among patients in CORE 2005. Clinical outcomes among OPAT patients appeared at least as good as or better than IPAT patients. Better outcomes among OPAT patients were most likely because of patient selection for OPAT. Additional studies should focus on clinical characteristics of patients who would be ideal candidates for daptomycin OPAT.

A pilot study of high-dose short duration daptomycin for the treatment of patients with complicated skin and skin structure infections caused by gram-positive bacteria.

BACKGROUND: Methicillin-susceptible and -resistant (MRSA) Staphylococcus aureus are significant causes of complicated skin and skin structure infections (cSSSI). The bactericidal antibiotic daptomycin is approved for gram-positive cSSSI at 4 mg/kg/day for 7-14 days, but the optimal dose level and duration of therapy have not been firmly established. This pilot study evaluated the efficacy and safety of daptomycin at 10 mg/kg every 24 h for 4 days [high-dose short duration (HDSD) regimen] vs. standard of care therapy with vancomycin or semi-synthetic penicillin for the treatment of cSSSI. METHODS: This was a semi-single blind, randomised, multicentre, comparative trial. The primary efficacy end-point was the clinical response 7-14 days posttherapy. RESULTS: One hundred patients were randomised; 48 in each arm were treated. The treatment groups were well balanced with respect to demographics, comorbidities and the type of infection (75% because of MRSA). Overall, clinical success rates were 75.0% (36/48) for daptomycin and 87.5% (42/48) for comparator (95% confidence interval for the difference: -27.9, 2.9). The median duration of comparator therapy was 8 days. Two comparator patients and no daptomycin patients experienced treatment-related serious adverse events requiring hospitalisation. CONCLUSION: We found that the HDSD regimen had a safety profile similar to that seen in previous studies. Although the differences were not statistically significant, clinical success rates for comparator were higher than for daptomycin. In post hoc analyses HDSD daptomycin performed better in some subgroups (e.g. outpatients) than in others (e.g. certain MRSA infections). These observations require confirmation in larger trials.

Prolonged outbreak of giardiasis with two modes of transmission.

Large outbreaks of giardiasis caused by person-to-person transmission, or a combination of transmission routes, have not previously been reported. A large, prolonged giardiasis outbreak affected families belonging to a country club in a suburb of Boston, Massachusetts, during June-December 2003. We conducted a retrospective cohort study to determine the source of this outbreak. Giardiasis-compatible illness was experienced by 149 (25%) respondents to a questionnaire, and was laboratory confirmed in 97 (65%) of these cases. Of the 30 primary cases, exposure to the children's pool at the country club was significantly associated with illness (risk ratio 3.3, 95% confidence interval 1.7-6.5). In addition, 105 secondary cases probably resulted from person-to-person spread; 14 cases did not report an onset date. This outbreak illustrates the potential for Giardia to spread through multiple modes of transmission, with a common-source outbreak caused by exposure to a contaminated water source resulting in subsequent prolonged propagation through person-to-person transmission in the community. This capacity for a common-source outbreak to continue propagation through secondary person-to-person spread has been reported with Shigella and Cryptosporidium and may also be a feature of other enteric pathogens having low infectious doses.

Parasitic infections of the gastrointestinal tract.

This article updates recent advances in the body of knowledge of diagnosis and treatment of intestinal parasites. The articles focus on the manifestations of disease in the immunocompetent adult host from developed countries. Specific pathogens discussed are Giardia lamblia and Dientamoeba fragilis, Entamoeba histolytica, Entamoeba dipar, Blastocystis hominis, Cyclospora cayetanensis, and Cryptosporidium parvum.

Factors that influence outcome in bracing large curves in patients with adolescent idiopathic scoliosis.

STUDY DESIGN: A retrospective review of 51 patients with adolescent idiopathic scoliosis (AIS) treated with a Boston brace for curves ranging from 36 degrees to 45 degrees. OBJECTIVES: To determine what radiographic or clinical observations may be predictive of outcome. SUMMARY OF BACKGROUND DATA: Patients with AIS who are braced for curves >35 degrees are less likely to respond to conservative treatment than patients of similar maturity with smaller curves. METHODS: Skeletally immature patients with AIS with no history of prior treatment were treated with a Boston brace. Cobb angles, vertebral tilt angles, coronal decompensation, apical vertebral translation(s), apical vertebral rotation, lateral trunk shift, rib vertebral angle difference, pelvic tilt, and the lumbar pelvic relationship (LPR) were measured at brace prescription, initial in-brace, brace discontinuation, and follow-up. RESULTS: At the time of brace discontinuation, 31 patients (61%) were judged treatment successes. With follow-up observation, an additional eight patients progressed beyond 5 degrees, and a total of 16 patients (31%) required surgical correction. Only patients with double curves were found to have radiographic values predictive of outcome. The LPR angle, the association between the thoracic curve vertebral tilt angles and the amount of in-brace correction of the Cobb angle, were significant predictors. A patient's reported wear schedule significantly influenced outcome. CONCLUSIONS: Patients with a double curve pattern in which the thoracic curve is >35 degrees and the LPR angle is >12 degrees are significantly more likely to demonstrate curve progression. In-brace correction for double curves of at least 25% and a patient's ability to wear the orthosis >18 hours/day significantly increased the likelihood of success.

Development of a ceuE-based multiplex polymerase chain reaction (PCR) assay for direct detection and differentiation of Campylobacter jejuni and Campylobacter coli in Thailand.

A novel ceuE-based multiplex PCR system was developed as an efficient diagnostics test to detect and differentiate C. jejuni and C. coli. There is no cross reactivity between C. jejuni and C. coli. In addition, the assay does not produce a positive signal from other enteric bacteria including Salmonella, Shigella and Escherichia coli strains. Campylobacter detection sensitivity was determined to be equivalent to previously reported PCR for other enteric bacteria. We also noticed that silicon dioxide extraction can improve Campylobacter detection sensitivity from infected stool samples. It was demonstrated that the PCR assay developed in this study had a much better Campylobacter detection rate than the traditional culturing method (77% versus 56%). However, we also identified small numbers of culture positive stools (8%, or 16 out of 202 samples) that did not yield PCR positive results for Campylobacter. These PCR negative/culture positive stools were proven to be inhibitory to PCR amplification.

Regulatory and educational initiatives fail to promote discussions regarding end-of-life care.

We conducted an observational cohort study to determine if hospital-based, reinforcing regulatory and educational interventions could encourage physicians to discuss end-of-life (EOL) care with their patients. Specifically, we measured the effect of (1) administrative prompts to encourage discussions about EOL care and (2) a mandatory educational seminar focusing on EOL issues. Study subjects were patients consecutively admitted to the medicine service who faced an anticipated 3-year mortality rate of at least 50%. The main study endpoint was the frequency of documented EOL discussions between physicians and patients. In the inception cohort of 184 patients, physicians discussed EOL care with 64 patients (34. 8%), and in the follow-up cohort of 121 patients, 41 individuals (33. 9%) had documented discussions regarding EOL issues (P = 0.90). Actual "Do Not Resuscitate"(DNR) orders were written for 53 patients (28.8%) in the inception cohort and for 33 persons (27.3%) in the follow-up cohort (P = 0.71). We conclude that enhanced, mutually reinforcing regulatory and educational efforts focusing on EOL care proved ineffectual at promoting either discussions about EOL issues or the use of DNR orders.

Adrenal masses are associated with familial adenomatous polyposis.

PURPOSE: Although its defining feature is the development of multiple large-bowel polyps, familial adenomatous polyposis is a generalized disorder of tissue growth regulation, with a range of manifestations. An association between adrenal neoplasms and familial adenomatous polyposis has been suggested, but not prospectively documented. Patients with familial adenomatous polyposis were therefore screened to determine the frequency of adrenal masses. METHODS: Patients with familial adenomatous polyposis underwent spiral abdominal CT scan reported by two radiologists specialized in cross-sectional imaging. RESULTS: One hundred seven individuals were examined (median age, 36 (interquartile range, 30-48) years; 57 male). Fourteen (13 percent) had an adrenal mass of 1 cm or greater (bilateral in one case); none had clinical evidence of endocrine disturbance or hypertension. Two lesions were histologically confirmed adrenocortical adenomas and one a phaeochromocytoma; the remaining 12 had CT appearances of nonhyperfunctioning adrenocortical adenoma. CONCLUSIONS: The prevalence of unsuspected adrenal masses in the general population is approximately three percent. This prospective study found a significantly higher frequency of 13 percent in patients with familial adenomatous polyposis (chi-squared = 6.973; df = 1; P = 0.008). There is no evidence that the histologic nature of these differs from that in the general population.

Identification and progression of a desmoid precursor lesion in patients with familial adenomatous polyposis.

BACKGROUND: Desmoid tumours occur in about 10 per cent of patients with familial adenomatous polyposis (FAP), and are an important cause of morbidity and death. The natural history of desmoids was investigated by documenting prospectively the prevalence and progression of possible precursor lesions. METHODS: A group of patients with FAP and controls were examined at laparotomy. Another group, with FAP and no clinical evidence of desmoid, and a group of controls, underwent abdominopelvic computed tomography. RESULTS: At laparotomy 13 of 42 patients with FAP had fibromatous mesenteric plaques; seven of these had not had surgery. Seven had more extensive mesenteric fibromatosis and had undergone significantly more laparotomies than the rest. Of 103 patients scanned, two had desmoid tumours and 22 (21 per cent) had mesenteric fibromatosis. On follow-up both desmoid tumours grew rapidly; mesenteric fibromatosis was unchanged in eight and resolved in four of the 12 patients rescanned. CONCLUSION: A model of desmoid tumour development is suggested, analogous to the adenoma-carcinoma sequence, in which a less benign phenotype emerges as molecular genetic abnormalities accumulate: mesenteric plaque-like desmoid precursor lesions arise in many patients with FAP before surgery as a result of abnormal fibroblast function; some, perhaps stimulated by surgery, progress to mesenteric fibromatosis; these in turn can give rise to desmoid tumours.

Effectiveness of brace treatment in early infantile Blount's disease.

In an effort to determine whether bracing is effective in reversing early infantile Blount's disease, 27 patients with Langenskiold stage II disease were studied. Ten patients had bilateral disease (two of these patients had stage III disease affecting one side). Age at brace initiation averaged 2.1 years (range, 1.5-3.2). The duration of bracing averaged 9.7 months. Follow-up averaged 5.9 years. Successful outcomes (improved alignment without the need for osteotomy) were achieved in 19 (70%) patients, the majority of them having unilateral disease. Of the 37 affected extremities, 24 (65%) had successful outcomes. Eight patients (13 extremities) required tibial osteotomies and were classified as bracing failures. Of the 10 patients with bilateral involvement, seven (70%) required osteotomies for one or both extremities, whereas only one (6%) of 17 patients with unilateral involvement required osteotomy. Bracing appears to be effective in stage II infantile Blount's disease, particularly in those with unilateral involvement. Children with bilateral disease are most at risk for requiring subsequent corrective osteotomy.

A comparison between the Boston brace and the Charleston bending brace in adolescent idiopathic scoliosis.

STUDY DESIGN: The authors studied 319 patients with adolescent idiopathic scoliosis treated at the same institution with either a Boston brace or a Charleston bending brace. OBJECTIVES: To determine if both orthoses are equally effective in stopping curve progression and preventing the need for surgical correction. SUMMARY OF BACKGROUND DATA: Early reports suggest that the Charleston brace may be comparable to the Boston brace in its effectiveness and that both braces positively influence the natural history of idiopathic scoliosis. METHODS: Skeletally immature (Risser 0, 1, or 2) patients with idiopathic scoliosis who were 10 years old or older at the time of brace prescription, had curves from 25 degrees to 45 degrees, and had no prior treatment were studied retrospectively. All measurements were collected by a single observer, and all patients were followed up to skeletal maturity. RESULTS: The Boston brace is more effective than the Charleston brace, both in preventing curve progression and in avoiding the need for surgery. These findings were most notable for patients with curves of 36 degrees-45 degrees, in whom 83% of the those treated with a Charleston brace had curve progression of more than 5 degrees, compared with 43% of those treated with the Boston brace (p < 0.0001). CONCLUSION: When given the choice between these two orthoses in the treatment of adolescent idiopathic scoliosis, the authors recommend use of the Boston brace. The Charleston brace should be considered only in the treatment of smaller single thoracolumbar or single lumbar curves.

Comparative study of conventional hip-knee-ankle-foot orthoses versus reciprocating-gait orthoses for children with high-level paraparesis.

We evaluated eight children with thoracic or high lumbar-level paraparesis for metabolic performance while ambulating with custom fabricated thermoplastic hip-knee-ankle-foot orthoses (HKAFOs) and reciprocating-gait orthoses (RGOs). Seven of the eight children had myelomeningocele. Each patient was tested in both systems at self-selected speeds in a crossover study design. At self-selected speeds, the level of exercise intensity for both thoracic and high-lumbar patients with either orthosis was lower than that for normal children. The average metabolic cost of walking in the RGO was twice that of normal children, as compared with six times normal in HKAFOs. For the four thoracic-level patients, there was a significantly higher oxygen cost of ambulation in using HKAFOs versus RGOs. No significant difference in metabolic performance was found for the high-lumbar patients. Velocity of ambulation was faster in the RGOs than in the HKAFOs. For thoracic-level patients, our data suggest that an RGO will provide a faster, more energy-efficient gait than a statically locked HKAFO. For high-lumbar patients, no significant difference was found between the two orthoses. Seven of eight children preferred the RGO over the HKAFO.

The natural history of sciatica associated with disc pathology. A prospective study with clinical and independent radiologic follow-up.

The purpose of this study was to assess the natural history of sciatica due to lumbosacral nerve root compromise and to evaluate the pathomorphologic changes that accompany the natural resolution of the disease. One hundred sixty-five consecutive patients, 114 males and 51 females, with an average age of 41 years (range, 17-72) and an average duration of symptoms of 4.2 months (range, 1-72) presenting with sciatica thought to be due to lumbosacral nerve root compromise were admitted to the study. The cornerstone of treatment was the serial epidural administration of steroid and local anesthetic by the caudal route on an outpatient basis. Lumbar epidural injection or periradicular infiltration at the appropriate level, confirmed under image intensifier, was the next step before considering surgical decompression. An average of three injections (range, 0-8) was received by each patient. Patients underwent clinical examination and computed tomography. Twenty-three patients (14%) underwent surgical decompression. The remainder were clinically assessed at 1 year after presentation, and 111 were rescanned at the appropriate levels. All conservatively managed patients made a satisfactory clinical recovery: average reduction of pain on the visual analog scale was 94% (range, 45-100), and 64 (76%) of the 84 disc herniations and 7 (26%) of the 27 disc bulges showed partial or complete resolution (chi-square = 20.27, P = 0.0001). Thus a high proportion of patients with discogenic sciatica make a satisfactory recovery with aggressive conservative management, and this recovery is accompanied by resolution of disc herniations in a significant number. Only a small proportion of patients needed surgical decompression.

The natural history of sciatica: a prospective radiological study.

This prospective study was set up to record the changes in the intervertebral disc accompanying resolution of sciatica following conservative treatment. Patients presenting with sciatica (n = 165) were examined by computed tomography (CT) of the lumbar spine. Disc lesions were classified into the following groups: herniation, sequestration, generalized bulge and focal bulge. Follow-up CT of the pathological disc was performed in 106 of the 165 patients after 1 year and identical anatomical sections were compared. All patients were initially treated conservatively by the injection of steroid and local anaesthetic at the intervertebral disc/nerve root interface. Of 84 cases of disc herniation and sequestration 64 (76%) showed either complete or partial resolution on follow-up CT examination. Of 22 cases with either a generalized or focal bulge of the disc 18 (82%) were unchanged on follow up. The classical disc herniation in a young patient is the type of disc lesion most likely to show greatest improvement at follow-up CT.