Intravenous fosfomycin as salvage therapy for osteomyelitis caused by multidrug-resistant Pseudomonas aeruginosa.

PURPOSE: A case of osteomyelitis caused by multidrug-resistant (MDR) Pseudomonas aeruginosa is reported. SUMMARY: An 84-year-old Caucasian male with an underlying history of type 2 diabetes, peripheral vascular disease, and coronary artery disease had chronic nonhealing wounds on his right foot. Wound care and a course of intravenous (IV) ertapenem with oral ciprofloxacin were ineffective. His initial wound culture grew Staphylococcus aureus, group G streptococcus and P. aeruginosa; the Pseudomonas was susceptible to multiple agents. The patient eventually required midtarsal amputation and angioplasties to his right leg. Twenty days after the operation, 2 openings were discovered at the surgical site, 1 of which was probed to the bone. He was readmitted 5 weeks after the operation. A repeat wound swab grew MDR P. aeruginosa and Finegoldia magna. The Pseudomonas was susceptible to gentamicin and colistin. The patient had revision of the infected amputation site with the goal of salvaging his right lower limb. The patient developed acute renal failure after 26 days of IV gentamicin, IV ceftriaxone, and oral metronidazole. Additional susceptibility testing was performed to identify alternatives. The bacteria were considered susceptible to IV fosfomycin, the last resort, by our microbiology laboratory. This was combined with ceftolozane/tazobactam followed by meropenem to treat the residual infection. After 2 weeks of IV fosfomycin, the patient's wound improved and further amputation was avoided. CONCLUSION: Our case demonstrates that IV fosfomycin may provide an effective salvage therapy when combined with ß-lactams for the treatment of severe diabetic foot infection or osteomyelitis caused by MDR P. aeruginosa.

Editorial Expression of Concern: Comparative effectiveness of ß-lactam versus vancomycin empiric therapy in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.

An amendment to this paper has been published and can be accessed via the original article.

Expression of Concern to: Comparison of outcomes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia who are treated with ß-lactam vs vancomycin empiric therapy: a retrospective cohort study.

An amendment to this paper has been published and can be accessed via the original article.

Antimicrobial stewardship for hospitalized patients with viral respiratory tract infections.

BACKGROUND: The purpose of this study was to implement a targeted antimicrobial stewardship intervention for patients with a viral respiratory tract infection. METHODS: This was a quasi-experimental before and after audit and feedback intervention of adult inpatients with a positive polymerase chain reaction for a respiratory virus in 2 acute care hospitals in Vancouver, Canada. Audit and feedback was implemented based on 2 criteria: microbiology (no positive bacterial cultures) and chest imaging (absence of pneumonia or consolidation on radiology dictation). A chart review was conducted to assess for days of antibiotics postviral diagnosis. Outcomes including length of stay, intensive care unit admission within 14 days, mechanical ventilation within 14 days, antibiotics prescribed within 14 days, Clostridium difficile infection diagnosed within 30 days, and readmission within 30 days were also reviewed in comparison with the previous year. RESULTS: Antimicrobial stewardship recommendations for hospitalized patients with viral respiratory tract infections were accepted for 77% of cases. This targeted approach based on easily assessed parameters translated into a 1.3-day (95% confidence interval, 0.3-2.3; P < .01) decrease in mean days of antibiotics postviral diagnosis compared with the previous year without systematic interventions. Compared with the previous year, no differences were identified for adverse outcomes associated with the intervention. CONCLUSIONS: A targeted antimicrobial stewardship intervention integrating virology testing with the treating physician facilitated a reduction in duration of antibiotic treatment for viral respiratory tract infections.

Alternative Cardiac Imaging Modalities to Echocardiography for the Diagnosis of Infective Endocarditis.

Infective endocarditis (IE) is a life-threatening disease. Considered the gold standard for the diagnosis of IE, the modified Duke criteria rely on echocardiographic findings to satisfy its major criterion. Echocardiography is an invaluable tool in the evaluation of patients with suspected IE but suffers from certain limitations. For example, it cannot differentiate vegetation from clot, or between infected and noninfected vegetation, and may miss vegetation and periannular extensions in the presence of prosthetic material. Therefore, alternative cardiac imaging modalities are needed. Nuclear imaging, particularly 18F-fluorodesoxyglucose positron emission tomography-computed tomography (CT), is becoming increasingly popular in the evaluation of patients for IE and has shown promise in diagnosing valvular and device-related IE when echocardiography results were inconclusive. Other techniques such as radiolabeled leukocyte scintigraphy and single-photon emission computed tomography with or without CT are less well studied, however. Cardiac CT angiography is also evolving as a powerful supplementary tool to echocardiography for the detection of perivalvular complications of IE and for preoperative evaluation of coronary anatomy. The combination of cardiac CT angiography and echocardiography is superior to either test alone in the diagnosis of IE and its complications. Although brain magnetic resonance imaging may impact prognosis and clinical management by identifying cerebral emboli in patients with IE, the role of cardiac and abdominal magnetic resonance imaging is less clear. In conclusion, with these additional diagnostic tools at our disposal, the diagnosis of IE may be achieved in a more timely and accurate manner to secure better clinical outcomes.

Comparison of outcomes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia who are treated with ß-lactam vs vancomycin empiric therapy: a retrospective cohort study.

BACKGROUND: Prior studies suggested that vancomycin may be inferior to ß-lactams for the empiric treatment of methicillin-susceptible S. aureus (MSSA) bacteremia. We assessed whether empiric therapy with ß-lactams compared to vancomycin was associated with differences in clinical outcomes in patients with MSSA bacteremia. METHODS: We conducted a retrospective cohort study of adult inpatients with their first episode of MSSA bacteremia at two tertiary care hospitals in Vancouver, Canada, between 2007 and 2014. Exposure was either empiric ß-lactam or vancomycin therapy. All patients received definitive treatment with cloxacillin or cefazolin. The primary outcome was 28-day mortality. Secondary outcomes were 90-day mortality, recurrent infection at 6 months, duration of bacteremia and hospital length-of-stay. Outcomes were adjusted using multivariable logistic regression. RESULTS: Of 814 patients identified, 400 met inclusion criteria (ß-lactam = 200, vancomycin = 200). Overall 28-day mortality was 8.5 % (n=34). There were more cases of infective endocarditis in the ß-lactam than in the vancomycin group [45 (22.5 %) vs 23 (11.5 %), p < 0.01]. Adjusted mortality at 28 days was similar between the two groups (OR: 1.14; 95 % CI: 0.49-2.64). No differences in secondary outcomes were observed. Transition to cloxacillin or cefazolin occurred within a median of 67.8 h in the vancomycin group. CONCLUSIONS: Empiric therapy with ß-lactams was not associated with differences in all-cause mortality, recurrent infection, microbiological cure or hospital length-of-stay compared to vancomycin. Vancomycin monotherapy may be appropriate for the empiric treatment of MSSA bacteremia if definitive therapy with cloxacillin or cefazolin can be initiated within 3 days.

Comparative effectiveness of ß-lactam versus vancomycin empiric therapy in patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.

BACKGROUND: Vancomycin may be inferior to ß-lactams for the empiric treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We compared empiric ß-lactams to vancomycin to assess clinical outcomes in patients with MSSA bacteremia. METHODS: We conducted a retrospective cohort study of adult inpatients with their first episode of MSSA bacteremia at two tertiary care hospitals in Vancouver, Canada, between 2007 and 2014. Exposure was either empiric ß-lactam with or without vancomycin or vancomycin monotherapy. All patients received definitive treatment with cloxacillin or cefazolin. The primary outcome was 28-day mortality. Secondary outcomes were 90-day mortality, duration of bacteremia, and hospital length-of-stay. Outcomes were adjusted using multivariable logistic regression. RESULTS: Of 669 patients identified, 255 met inclusion criteria (ß-lactam = 131, vancomycin = 124). Overall 28-day mortality was 7.06 % (n = 18). There were more cases of infective endocarditis in the ß-lactam than in the vancomycin group [24 (18.3 %) vs 12 (9.7 %), p = 0.05]. Adjusted mortality at 28 days was similar between the two groups (OR 0.85; 95 % CI 0.27-2.67). The duration of bacteremia was longer in the vancomycin group (97.1 vs 70.7 h, p = 0.007). Transition to cloxacillin or cefazolin occurred within a median of 68.3 h in the vancomycin group. CONCLUSIONS: Empiric ß-lactams was associated with earlier clearance of bacteremia by a median of 1 day compared to vancomycin. Future prospective studies are needed to confirm our findings.

Subacute bacterial endocarditis caused by Cardiobacterium hominis: A case report.

Cardiobacterium hominis, a member of the HACEK group of organisms, is an uncommon but important cause of subacute bacterial endocarditis. First-line therapy is a third-generation cephalosporin due to rare beta-lactamase production. The authors report a case involving endovascular infection due to C hominis that initially tested resistant to third-generation cephalosporins using an antibiotic gradient strip susceptibility method (nitrocephin negative), but later proved to be susceptible using broth microdilution reference methods (a 'major' error). There are limited studies to guide susceptibility testing and interpretive breakpoints for C hominis in the medical literature, and the present case illustrates some of the issues that may arise when performing susceptibility testing for fastidious organisms in the clinical microbiology laboratory.

Le Cardiobacterium hominis, qui appartient aux organismes du groupe HACEK, est une cause d'endocardite bactérienne subaiguë peu fréquente, mais importante. La céphalosporine de troisième génération en est le traitement de première ligne, en raison d'une rare production de bêta-lactamase. Les auteurs rendent compte d'un cas d'infection endovasculaire à C hominis qui a d'abord été considéré comme résistant aux céphalosporines de troisième génération d'après la méthode de susceptibilité par bandelette contenant un gradient d'antibiotique (négative à la nitrocéphine), mais qui s'y est révélé susceptible selon les méthodes de microdilution de référence (une erreur « majeure ¼). Peu de publications traitent des études pour orienter les tests de susceptibilité et les seuils d'interprétation du C hominis, et le présent cas démontre quelques problèmes qui peuvent surgir lors de tests de susceptibilité d'organismes difficiles à isoler au laboratoire de microbiologie clinique.

Bacteremia caused by Eggerthella lenta in an elderly man with a gastrointestinal malignancy: A case report.

Eggerthella lenta is an anaerobic, Gram-positive bacillus commonly found in the human digestive tract. Occasionally, it can cause life-threatening infections. Bacteremia due to this organism is always clinically significant and is associated with gastrointestinal diseases and states of immune suppression. The authors report a case involving an elderly man with a newly diagnosed gastrointestinal malignancy who developed bacteremia caused by E lenta, treated successfully using empirical therapy with vancomycin and piperacillin-tazobactam, followed by directed therapy with metronidazole once the identity and antibiotic susceptibility of the organism was established. The present case reinforces the connection between E lenta bacteremia with gastrointestinal malignancy and highlights the importance of searching for a source of bacteremia due to this organism.

L'Eggerthella lenta est un bacille anaérobique à Gram positif présent dans le tube digestif humain. Il cause parfois des infections au potentiel mortel. La bactériémie attribuable à cet organisme est toujours grave sur le plan clinique et s'associe à des maladies gastro-intestinales et à des états immunosuppressifs. Les auteurs présentent le cas d'un homme âgé atteint d'un cancer gastro-intestinal diagnostiqué qui a souffert d'une bactériémie causée par l'E lenta et qui a reçu un traitement empirique fructueux à la vancomycine et à la pipéracilline-tazobactam, suivi d'une thérapie dirigée au métronidazole une fois l'organisme connu et la susceptibilité à l'organisme établie. Ce cas renforce le lien entre la bactériémie causée par l'E lenta et le cancer gastro-intestinal et fait ressortir l'importance d'en chercher la source.

Sedation and analgesia usage in severe pandemic H1N1 (2009) infection: a comparison to respiratory failure secondary to other infectious pneumonias.

BACKGROUND: During the 2009 H1N1 pandemic (pH1N1), patients requiring mechanical ventilation for respiratory failure received high doses of sedation and analgesia. OBJECTIVE: To examine sedation and analgesia use among patients with respiratory failure due to severe pH1N1 infection compared to other infectious pneumonias. METHODS: In this observational cohort study of intensive care unit (ICU) patients with respiratory failure, we compared doses of sedatives and analgesics administered to patients with pH1N1, non-pH1N1 viral pneumonia, and adult respiratory distress syndrome (ARDS) secondary to bacterial pneumonia, on days 1, 3, 7, 14, and 28 of ICU admission. Cumulative drug use, daily drug use, and weight-adjusted medication doses were examined. RESULTS: The study population consisted of 37 patients with pH1N1 infection, 22 patients with non-pH1N1 viral pneumonia, and 46 patients with ARDS secondary to bacterial pneumonia. To achieve similar levels of sedation using the Richmond Agitation Sedation Scale, patients with pH1N1 were administered the highest cumulative median doses of fentanyl (11,230 µg; interquartile range [IQR] 3240-21,000), compared to 2400 µg (IQR 130-7130) in viral pneumonia and 2880 µg (IQR 600-6950) in ARDS (p < 0.001). Patients with pH1N1 were also administered the highest cumulative median doses of midazolam at 820 mg (IQR 330-1160), compared to 160 mg (IQR 20-390) in viral pneumonia and 160 mg (IQR 20-480 mg) in ARDS (p < 0.001). The pH1N1 group received the highest median daily fentanyl and midazolam doses on all study days. The pH1N1 group did not differ significantly in cumulative propofol dose compared with the other 2 study groups. CONCLUSIONS: Sedative and analgesic use may be uniquely higher in critically ill patients with pH1N1 infection compared to patients with other infectious pneumonias. This finding may be important for resource planning in future pandemics. Further study is required to explore the underlying mechanisms for potentially higher sedative and analgesic requirements in this patient population.

Tail suspension increases energy expenditure independently of the melanocortin system in mice.

Space travelers experience anorexia and body weight loss in a microgravity environment, and microgravity-like situations cause changes in hypothalamic activity. Hypothalamic melanocortins play a critical role in the regulation of metabolism. Therefore, we hypothesized that microgravity affects metabolism through alterations in specific hypothalamic signaling pathways, including melanocortin signaling. To address this hypothesis, the microgravity-like situation was produced by an antiorthostatic tail suspension in wild-type and agouti mice, and the effect of tail suspension on energy expenditure and hypothalamic gene expression was examined. Energy expenditure was measured using indirect calorimetry before and during the tail suspension protocol. Hypothalamic tissues were collected for gene expression analysis at the end of the 3 h tail suspension period. Tail suspension significantly increased oxygen consumption, carbon dioxide production, and heat production in wild-type mice. Tail suspension-induced increases in energy expenditure were not attenuated in agouti mice. Although tail suspension did not alter hypothalamic proopiomelanocortin (POMC) and agouti-related protein (AGRP) mRNA levels, it significantly increased hypothalamic interleukin 6 (Il-6) mRNA levels. These data are consistent with the hypothesis that microgravity increases energy expenditure and suggest that these effects are mediated through hypothalamic signaling pathways that are independent of melanocortins, but possibly used by Il-6.

Xenin, a gastrointestinal peptide, regulates feeding independent of the melanocortin signaling pathway.

OBJECTIVE: Xenin, a 25-amino acid peptide, was initially isolated from human gastric mucosa. Plasma levels of xenin rise after a meal in humans, and administration of xenin inhibits feeding in rats and chicks. However, little is known about the mechanism by which xenin regulates food intake. Signaling pathways including leptin and melanocortins play a pivotal role in the regulation of energy balance. Therefore, we addressed the hypothesis that xenin functions as a satiety factor by acting through the melanocortin system or by interacting with leptin. RESEARCH DESIGN AND METHODS: The effect of intracerebroventricular and intraperitoneal administration of xenin on food intake was examined in wild-type, agouti, and ob/ob mice. The effect of intracerebroventricular injection of SHU9119, a melanocortin receptor antagonist, on xenin-induced anorexia was also examined in wild-type mice. To determine whether the hypothalamus mediates the anorectic effect of xenin, we examined the effect of intraperitoneal xenin on hypothalamic Fos expression. RESULTS: Both intracerebroventricular and intraperitoneal administration of xenin inhibited fasting-induced hyperphagia in wild-type mice in a dose-dependent manner. The intraperitoneal injection of xenin also reduced nocturnal intake in ad libitum-fed wild-type mice. The intraperitoneal injection of xenin increased Fos immunoreactivity in hypothalamic nuclei, including the paraventricular nucleus and the arcuate nucleus. Xenin reduced food intake in agouti and ob/ob mice. SHU9119 did not block xenin-induced anorexia. CONCLUSIONS: Our data suggest that xenin reduces food intake partly by acting through the hypothalamus but via signaling pathways that are independent of those used by leptin or melanocortins.

Regulation of hepatic PPARgamma2 and lipogenic gene expression by melanocortin.

The central melanocortin system regulates hepatic lipid metabolism. Hepatic lipogenic gene expression is regulated by transcription factors including sterol regulatory element-binding protein 1c (SREBP-1c), carbohydrate responsive element-binding protein (ChREBP), and peroxisome proliferator-activated receptor gamma2 (PPARgamma2). However, it is unclear if central melanocortin signaling regulates hepatic lipogenic gene expression through the activation of these transcription factors. To delineate the molecular mechanisms by which the melanocortin system regulates hepatic lipid metabolism, we examined the effect of intracerebroventricular injection of SHU9119, a melanocortin receptor antagonist, on hepatic expression levels of genes involved in lipid metabolism in mice. SHU9119 treatment increased hepatic triglyceride content and mRNA levels of lipogenic genes, SREBP-1c, and PPARgamma2, whereas it did not cause any changes in hepatic ChREBP mRNA levels. These findings suggest that reduced central melanocortin signaling increases hepatic lipid deposition by stimulating hepatic lipogenic gene expression at least partly through the activation of SREBP-1c and PPARgamma2.