Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections associated with surgical procedures

Background

We compared telavancin with vancomycin for the treatment of complicated skin and skin-structure infections (cSSSI) caused by Gram-positive bacteria.

Methods

This was a retrospective analysis of clinical and microbiologic efficacy assessed at test-of-cure (7 to 14 days after completing therapy) in 194 patients from 2 randomized, double-blind clinical trials comparing telavancin (10 mg/kg intravenous [IV] every 24 hours; n = 101) with vancomycin (1 g IV every 12 hours; n = 93) for the treatment of cSSSI.

Results

Baseline characteristics were similar for both treatment groups. Clinical cure and microbiologic eradication rates demonstrated consistent trends favoring telavancin over vancomycin; however, the differences were not statistically significant. The incidence of adverse events was mostly similar between groups.

Conclusions

The efficacy of telavancin was at least equivalent to that of vancomycin for the treatment of cSSSI. These data suggest that telavancin may be a useful alternative for treatment of cSSSI caused by S. aureus, particularly MRSA.     

Familial extrarenal Wilms tumor

Background/Purpose

This study aimed to illustrate the first report of extrarenal Wilms tumor occurring in a family.

Materials and methods

Retrospective case note review of 3 siblings, 2 of which presented with extrarenal Wilms tumor. Immunohistochemical analysis for WT1 gene product was performed together with molecular genetic linkage studies.

Results

A 3-year-old boy had excision of a right-sided extrarenal retroperitoneal Wilms tumor and nephrectomy followed by chemotherapy. At follow-up of 4 years, the boy was well and thriving.Aged 2 years, his sister developed a left-sided retroperitoneal extrarenal Wilms tumor. She had a tumor excision and nephrectomy followed by chemotherapy. She was well on follow-up more than a year after completion of treatment.Immunohistochemical analysis identified WT1 gene product within the tumor for both cases.Molecular genetic linkage studies showed no linkage between the index cases at FWT1 locus. Although possible linkage was demonstrated at WT1 locus, no mutation was found in the coding sequence and intron/exon boundaries of WT1 gene in index patient 1. A possible linkage between the index cases was also found at FWT2 locus. This could be a chance event because of the close relationship of the 2 patients.

Conclusions

We could identify extrarenal Wilms tumor in a family for the first time. Immunohistochemical analysis showed WT1 gene products in both cases. Linkage studies for Wilms tumor genes within the family were inconclusive. The possible linkage between the 2 index cases may be a chance event.     

Alpha glutathione S-transferase: a potential marker of ischemia-reperfusion injury of the intestine after cardiac surgery?

Background

The aim of the study was to assess the utility of α glutathione S-transferase (αGST) as a potential marker of intestinal ischemia-reperfusion injury in children after cardiac surgery.

Methods

Twenty-six patients undergoing cardiac surgery were enrolled in this longitudinal experimental study. Blood samples were drawn for analysis at specified time points during surgery and analyzed for αGST levels. Clinical indices of splanchnic morbidity were assessed up to discharge from hospital. Results were analyzed using Mann-Whitney tests and linear mixed effects models.

Results

Two groups were identified. Group 1 (n = 16) showed no intestinal morbidity and group 2 (n = 10) had signs of intestinal morbidity. Statistical differences were shown between the 2 groups with respect to time with aortic cross-clamp (ACC) in situ, time on cardiac bypass, duration of operation, time to enteral feeding and full feeding, time on mechanical ventilation, and time in the intensive care unit postoperatively. The serum concentration of αGST was significantly higher for group 2 and this rise was greatest after removal of the ACC.

Conclusions

αGST showed significant elevation in patients with prolonged bypass times and ACC times. These patients also displayed signs of intestinal morbidity, suggesting that this marker may be useful in screening patients at risk for intestinal pathology. This rise in αGST was associated with a prolonged ischemia time, and was greatest after the cross-clamp was released, suggesting that it is a postischemic reperfusion phenomenon leading to its elevation. A low αGST level appears to exclude significant intestinal ischemia.     

Biological diagnosis for neuroblastoma using the combination of highly sensitive analysis of prognostic factors

Background/Purpose

To select the optimal treatment according to the degree of malignancy of neuroblastoma, it is essential to accurately and rapidly identify any genetic abnormalities associated with the prognosis. This study aims to assess the correlation between the combination of prognostic factors and the biologic findings of neuroblastoma using a highly sensitive analysis of prognostic factors.

Methods

In 44 neuroblastoma primary samples, we determined the gene dosages of MYCN and Survivin (as the target of 17q gain) and the expression levels of MYCN, Survivin, and BIN1 using highly sensitive analysis (the quantitative polymerase chain reaction method); furthermore, we assessed the correlation between the combination of their prognostic factors and the biology of neuroblastoma.

Results

The gene dosage of MYCN or Survivin was significantly associated with all known prognostic factors. The expression level of MYCN or Survivin was not significantly associated with any prognostic factors, whereas the expression level of BIN1 was significantly associated with 5 of 6 prognostic factors. Regarding the combination of MYCN amplification and 17q gain (the gene dosage of Survivin), and the low expression of BIN1, the rates of advanced stages (stage III or IV) were 100% for the cases with 3 factors, 63% for the cases with 2 factors, 42% for the cases with 1 factor, and 0% for the cases with null factor. Furthermore, the survival rates were 20% for the cases with 3 factors, 50% for the cases with 2 factors, 100% for the cases with 1 factor, and 100% for the cases with null factor.

Conclusion

The combination of gene dosages of MYCN and Survivin and the expression level of BIN1 using the quantitative polymerase chain reaction method was significantly correlated with the clinical stage and the patients' outcome. This combination of biologic factors may enhance the accuracy to the conventional criteria, but this would have to be shown in a much larger study that is adequately powered to detect such an advantage.     

Targeting multiple angiogenic pathways for the treatment of neuroblastoma

Purpose

Resistance to angiogenesis inhibition can occur through the upregulation of alternative mediators of neovascularization. We used a combination of angiogenesis inhibitors with different mechanisms of action, interferon-β (IFN-β) and rapamycin, to target multiple angiogenic pathways to treat neuroblastoma xenografts.

Methods

Subcutaneous and retroperitoneal neuroblastoma xenografts (NB-1691 and SK-N-AS) were used. Continuous delivery of IFN-β was achieved with adeno-associated virus vector-mediated, liver-targeted gene transfer. Rapamycin was delivered intraperitoneally (5 mg/kg per day). After 2 weeks of treatment, tumor size was measured, and tumor vasculature was evaluated with intravital microscopy and immunohistochemistry.

Results

Rapamycin and IFN-β, alone and in combination, had little effect on tumor cell viability in vitro. In vivo, combination therapy led to fewer intratumoral vessels (69% of control), and the remaining vessels had an altered phenotype, being covered with significantly more pericytes (13× control). Final tumor size was significantly less than controls in all tumor models, with combination therapy having a greater antitumor effect than either monotherapy.

Conclusion

The combination of IFN-β and rapamycin altered the vasculature of neuroblastoma xenografts and resulted in significant tumor inhibition. The use of combinations of antiangiogenic agents should be further evaluated for the treatment of neuroblastoma and other solid tumors.     

Formula fortified with live probiotic culture reduces pulmonary and gastrointestinal bacterial colonization and translocation in a newborn animal model

Background/Purpose

Acidified diets are protective against intestinal bacterial colonization and translocation. Probiotic diets are designed to modulate the intestinal flora to enhance mucosal immunity. This study was designed to determine if formula acidified with live probiotic decreases bacterial gut colonization and translocation, and is equally tolerated as other acidified diets.

Methods

One hundred twenty-eight rabbit pups delivered via cesarean section [cesarean delivery, cesarean birth, abdominal delivery] were randomly assigned to 4 feeding groups: NAN Nestle (control, pH 7.0), NAN acidified with citric acid (pH 4.55), biologically acidified Pelargon (pH 4.55), and NAN with live Lactococcus lactis culture (pH 4.2). Pups were gavage fed every 12 hours with Enterobacter cloacae challenges of 10 colony-forming units/mL per feed and killed on day of life 3. Lungs, liver, spleen, mesenteric lymph nodes (MLNs), stomach, and cecum were cultured and quantitatively analyzed for target organism growth. Results were analyzed using χ² tests.

Results

NAN with live probiotic culture, when compared with Pelargon, acidified NAN, and NAN, significantly reduced the incidence of Enterobacter pulmonary colonization (P < .01), bacterial translocation (liver, P < .025; spleen and MLN, P < .05), and gastric and intestinal colonization (P < .001 for both).

Conclusion

Probiotic-fortified formula provides superior protection against pulmonary and gastrointestinal bacterial colonization and translocation compared with neutral and acidified formulas, and is equally tolerated.     

Description of Streptococcus pneumoniae infections in burn patients

Background

Longer survival in burn patients has resulted in more infectious complications, typically with Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Although Streptococcus pneumoniae infections are common in the community and can cause nosocomial infections, the incidence and risk factors for pneumococcal infections in burn patients is unclear.

Methods

We performed an electronic retrospective chart review to collect rates of and risk factors for S. pneumoniae infections in patients with thermal burns from March 2003 through June 2008.

Results

Of the 1838 patients admitted to the burn center, 10 were infected (0.54% incidence). Patients presented with pneumonia (seven patients, 0.38% incidence) and bacteremia (three patients, 0.16% incidence) within a week of initial burn (median 1 day, range 0–8), often in the setting of bacterial co-infection (five patients). This group was mainly young males with median 28.8% total body surface area burns; 60% had concomitant inhalational injury. Most did not have traditional risk factors for pneumococcal infection but had objective signs of infection at time of positive culture and were treated with appropriate antibiotics. Two patients in this series died, although no mortality was attributed to S. pneumoniae.

Conclusions

Pneumococcal disease is not common in burn patients and generally occurs early on in hospitalization after burn making it more likely to be a community-acquired pathogen rather than nosocomial in the burn population. It should be considered in the setting of sepsis or new pulmonary infiltrates within a week after burn, but typical empiric antibiotics against the usual burn pathogens should be adequate to also treat for pneumococcal infection.     

Preventing enterocyte apoptosis after massive small bowel resection does not enhance adaptation of the intestinal mucosa

Background

After massive small bowel resection (SBR), increased rates of enterocyte apoptosis are observed in the remnant bowel via a mechanism requiring bax gene expression. This study tested the hypothesis that adaptive mucosal growth could be enhanced by the novel strategy of preventing postresection enterocyte apoptosis.

Methods

Male bax-null and corresponding wild-type (WT) mice underwent a 50% proximal SBR or sham operation (bowel transaction with reanastomosis alone). Mice were killed after a full adaptation interval of 1 month. Adaptation was measured in the remnant ileum as alterations in villus height, crypt depth, and wet weight. Rates of enterocyte proliferation were derived by immunostaining of crypt enterocytes for Ki-67 and apoptosis by the presence of apoptosis bodies.

Results

The expected increase in enterocyte apoptosis after SBR occurred in the WT mice but was unchanged in the bax-null mice. Despite the prevention of postresection apoptosis in the bax-null mice, all parameters of adaptation and proliferation increased equally after SBR in both groups of mice.

Conclusions

Bax deficiency prevents the increase in enterocyte apoptosis that occurs after massive SBR throughout the entire adaptation period. Attenuation of postresection enterocyte apoptosis does not augment mucosal adaptation to massive intestinal loss.     

Clostridium difficile in hip fracture patients: Prevention, treatment and associated mortality

Background

A series of infection control measures were introduced at the University Hospitals of Leicester NHS Trust in 2006-2007 to reduce the incidence of Clostridium difficile infection.

Aim

The aim of this study was to assess the impact of these measures on the incidence of C. difficile and to record the associated mortality in hip fracture patients.

Patients and methods

A case matched comparison of mortality was conducted between C. difficile positive patients and C. difficile negative patients admitted with a hip fracture between 1st January 2003 and 30th September 2007. An interrupted time series analysis was performed to assess the effect of various infection control policies on the incidence of C. difficile infection.

Results

The interrupted time series analysis showed that the only effective measure was changing antimicrobial prophylaxis to Co-amoxiclav in May 2007. This reduced the incidence of C. difficile from 7.1 to 1.5% (p < 0.001). Six-month mortality in C. difficile positive patients was 71% 1 year before introduction of a diarrhoea treatment policy and 65% 1 year after (p = 0.5) indicating treatment was ineffective. A matched cohort comparison over a 57-month period from January 2003 to September 2007 showed that the 6-month mortality was 67% in 170 C. difficile positive patients, 27% in 3247 C. difficile negative patients and 29% in the 170 C. difficile negative matched patients.

Conclusion

This 38% excess mortality indicated that C. difficile increased mortality and did not simply colonise the sickest patients. Changing prophylaxis to Co-amoxiclav was the most effective measure. This reduced the incidence of C. difficile by 80% and thus reduced mortality by prevention rather than cure.     

The migrating gubernaculum grows like a "limb bud"

Background

The gubernaculum is crucial for testicular descent, and in the second, or inguinoscrotal, phase of descent it has no caudal attachments. Cranially, it is attached to the testis, but its caudal free tip migrates to the scrotum controlled by the genitofemoral nerve. Recent studies show active proliferation in the tip. We hypothesized that the gubernacular tip may grow like a limb bud.

Methods

We performed whole-mount in situ hybridization studies on male and female fetal mice (ages, E14.5-E18.5; n = 162) looking for limb bud regulatory factors.

Results

Our results showed that a member of the fibroblast growth factor (Fgf) family, Fgf10, and Hoxa10 were both expressed in the male gubernaculum at E14.5, and Hoxa10 was also expressed in the E16.5 mice. Weak staining was seen in the female gubernaculum for Hoxa10 on days E14.5 and E16.5, whereas no staining for Fgf10 was seen in the female gubernaculums.

Conclusions

These studies, although preliminary, suggest limb bud regulators are essential for gubernacular growth. Hox genes and Fgfs may be fruitful areas of research to unravel the molecular control of gubernacular migration during testicular descent.     

Attenuated Salmonella typhimurium with interleukin 2 gene prevents the establishment of pulmonary metastases in a model of osteosarcoma

Purpose

The current management of osteosarcoma (OS) entails an aggressive preoperative and postoperative chemotherapeutic regimen with limb salvage surgery. Despite these efforts, relapse-free survival is less than 60% in patients with classic OS, whereas most patients relapse with pulmonary metastases. In these studies, we sought to prevent the establishment of pulmonary metastases from OS with a single oral dose of SalpIL2.

Methods

Mice were administered attenuated Salmonella typhimurium with (SalpIL2) and without a gene for human interleukin 2 (Sal-NG) 7 days before challenge with 2 × 10⁵ OS cells via tail vein. Three weeks after injection, mice were harvested for splenic lymphocytes and tumor enumeration.

Results

Prophylaxis with attenuated SalpIL2 significantly reduces pulmonary metastases in number and volume (P < .0001 and P < .0001) with respect to saline controls. Furthermore, splenic natural killer cell populations were increased 396% with SalpIL2 (P < .0007) and 426% with Sal-NG (P < .0003) compared to nontreated groups.

Conclusions

Host natural killer response is greatly amplified and maybe partially responsible for the effective immune response against the formation of pulmonary metastases. A single oral dose of SalpIL2 may be a novel form of adjuvant therapy for patients after early detection of primary OS.     

Emergence of community-acquired methicillin-resistant Staphylococcus aureus soft tissue infections

Purpose

Our objective is to describe the changing incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and its treatment within East Tennessee.

Methods

A retrospective chart review of 245 patients treated with incision and drainage of soft tissue infections from March 2000 to September 2005 was completed. Consent was obtained from our local institutional review board. Forty patients were excluded because no cultures were recorded or because they failed the criteria for the diagnosis of CA-MRSA. We examined our data using χ² analysis. P value of less than .05 was considered statistically significant.

Results

The most common organism cultured was CA-MRSA (33%; 67 of 205). Non-CA-MRSA accounted for 4% (9 of 205). The age of patients ranged from 1 month to 21 years, with a mean age of 6.5 years. Stratified by year, the incidence of positive cultures for CA-MRSA has increased 159% since 2004 and 868% since 2003. In addition, the average age of patients has decreased from 8.3 years in 2000 to 6.1 years in 2005.

Conclusions

Community-acquired MRSA has emerged as the dominant source of soft tissue infection requiring incision and drainage regardless of site in East Tennessee. This has caused a change in the choice of empiric antibiotic treatment of soft tissue abscesses in our region. These infections now account for the third most common reportable disease to the Department of Health in East Tennessee.     

Strains of Klebsiella pneumoniae producing extended spectrum beta-lactamases, isolated from organ recipients

Objective

The aims of this work were to define the effectiveness of identification of the extended-spectrum beta-lactamases (ESBL) phenotype, and to define the genotype of Klebsiella pneumoniae β-lactamase.

Materials and Methods

We identified ESBL phenotypes in 110 strains of K pneumoniae isolated from samples from patients of transplantation wards, using the double-disk synergy test (DDST). For the chosen strains, polymerase chain reaction (PCR) was applied to detect genes determining SHV, CTX-M, and TEM.

Results

We showed synergism of clavulanic acid and investigated antibiotics including ceftazidime (89.1%), cefotaxime (80%), and aztreonam (82.7%) against ESBL-positive strains PCR revealed that TEM and CTX-M were present in 88.89% of strains.

Conclusions

The ESBL mechanism of resistance is frequent among K pneumoniae strains isolated from transplant recipients. Strains with simultaneous synthesis of more than one beta-lactamase predominated.     

An in vitro biofilm model to examine the effect of antibiotic ointments on biofilms produced by burn wound bacterial isolates

Purpose

Topical treatment of burn wounds is essential as reduced blood supply in the burned tissues restricts the effect of systemic antibiotics. On the burn surface, microorganisms exist within a complex structure termed a biofilm, which enhances bacterial resistance to antimicrobial agents significantly. Since bacteria differ in their ability to develop biofilms, the susceptibility of these biofilms to topically applied antibiotics varies, making it essential to identify which topical antibiotics efficiently disrupt or prevent biofilms produced by these pathogens. Yet, a simple in vitro assay to compare the susceptibility of biofilms produced by burn wound isolates to different topical antibiotics has not been reported.

Methods

Biofilms were developed by inoculating cellulose disks on agar plates with burn wound isolates and incubating for 24 h. The biofilms were then covered for 24 h with untreated gauze or gauze coated with antibiotic ointment and remaining microorganisms were quantified and visualized microscopically.

Results

Mupirocin and triple antibiotic ointments significantly reduced biofilms produced by the Staphylococcus aureus and Pseudomonas aeruginosa burn wound isolates tested, as did gentamicin ointment, with the exception of one P. aeruginosa clinical isolate.

Conclusions

The described assay is a practical and reproducible approach to identify topical antibiotics most effective in eliminating biofilms produced by burn wound isolates.     

Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus

Background

This open-label study compared oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA).

Methods

Patients with proven MRSA cSSTI were randomized to receive linezolid or vancomycin. Clinical and microbiologic outcomes, duration of antimicrobial therapy, length of hospital stay, and safety were assessed.

Results

In the per-protocol population, the rate of clinical success was similar in linezolid- and vancomycin-treated patients (P = .249). The rate of success was significantly higher in linezolid-treated patients in the modified intent-to-treat population (P = .048). The microbiologic success rate was higher for linezolid at the end of treatment (P < .001) and was similar at the end of the study (P = .127). Patients receiving linezolid had a significantly shorter length of stay and duration of intravenous therapy than patients receiving vancomycin. Both agents were well tolerated. Adverse events were similar to each drug's established safety profile.

Conclusions

Linezolid is an effective alternative to vancomycin for the treatment of cSSTI caused by MRSA.     

Staphylococcal colonization of caretakers of children who have community-acquired skin and soft tissue infections

Purpose

Colonization with Staphylococcus aureus is considered a risk factor for the rising incidence of pediatric community-acquired skin and soft tissue infections (CA-SSTIs), and intrafamily spread is thought to be the source of colonization.

Methods

A prospective study was conducted to determine skin and nasal staphylococcal colonization rates among the caretakers of CA-SSTI patients and those of nonabscess controls. A questionnaire regarding risk factors was administered to all participants. Fisher's Exact test and the χ² test were used for statistical analysis.

Results

Forty-six patients and their caretakers were enrolled in both the study and control groups. Of the caretakers in the study group, 19.6% (n = 9) had staphylococcal colonization of nares; and 2.2% (n = 1), skin. In the control group, 17.4% (n = 8) had nasal colonization; and none had skin colonization. Of the children in the study group, 58.7% (n = 27) had a family history of CA-SSTI compared with only 17.4% (n = 8) of controls (P = .0001). Of CA-SSTI patients, 45.7% (n = 21) had prior abscesses compared with 6.5% (n = 3) of controls (P = .0001). No other risk factor was identified.

Conclusion

There was no increase in nasal or skin staphylococcal colonization among caretakers of children with CA-SSTI. Family and personal histories of CA-SSTI were the only identified risk factors for CA-SSTI.     

Trends in the prevalence of Helicobacter pylori in symptomatic children in the era of eradication

Purpose

Helicobacter pylori infection is common in Asia and is associated with dyspepsia, peptic ulcer, and gastric cancer. Eradication of the organism remains an important goal. Here, we looked at the trends in the prevalence of H pylori in symptomatic children over an 8-year period to assess the impact of an aggressive eradication program.

Method

A retrospective review was carried out between 1997 and 2004. All children with a history of dyspepsia or acute gastrointestinal bleeding were included and underwent gastroscopy. Three antral biopsies were taken during endoscopy and sent for histological analysis. Positivity of H pylori was treated aggressively with quadruple therapy under protocol. The demographic data, the histological findings, and the H pylori status were recorded.

Results

There were a total of 159 patients (71 males, 88 females) who underwent gastroscopy in this period. One hundred nineteen patients showed histological evidence of gastritis, and the positive rate of H pylori was 25.6%. The overall prevalence has not decreased (33.3% in 1997, 27.7% in 2004). Increasing age, however, was associated significantly with the higher risk of H pylori infection.

Conclusion

H pylori has a high prevalence in Chinese children with increasing age. Eradication efforts seem to be unsuccessful in the reduction of prevalence. We hypothesize that this may be owing to cross-infection at meal times from sharing chopsticks.