Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017

IMPORTANCE: The human and financial costs of treating surgical site infections (SSIs) are increasing. The number of surgical procedures performed in the United States continues to rise, and surgical patients are initially seen with increasingly complex comorbidities. It is estimated that approximately half of SSIs are deemed preventable using evidence-based strategies. OBJECTIVE: To provide new and updated evidence-based recommendations for the prevention of SSI. EVIDENCE REVIEW: A targeted systematic review of the literature was conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library from 1998 through April 2014. A modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and the strength of the resulting recommendation and to provide explicit links between them. Of 5759 titles and abstracts screened, 896 underwent full-text review by 2 independent reviewers. After exclusions, 170 studies were extracted into evidence tables, appraised, and synthesized. FINDINGS: Before surgery, patients should shower or bathe (full body) with soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day. Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made. In cesarean section procedures, antimicrobial prophylaxis should be administered before skin incision. Skin preparation in the operating room should be performed using an alcohol-based agent unless contraindicated. For clean and clean-contaminated procedures, additional prophylactic antimicrobial agent doses should not be administered after the surgical incision is closed in the operating room, even in the presence of a drain. Topical antimicrobial agents should not be applied to the surgical incision. During surgery, glycemic control should be implemented using blood glucose target levels less than 200 mg/dL, and normothermia should be maintained in all patients. Increased fraction of inspired oxygen should be administered during surgery and after extubation in the immediate postoperative period for patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation. Transfusion of blood products should not be withheld from surgical patients as a means to prevent SSI. CONCLUSIONS AND RELEVANCE: This guideline is intended to provide new and updated evidence-based recommendations for the prevention of SSI and should be incorporated into comprehensive surgical quality improvement programs to improve patient safety.

Diagnosis and management of skin and soft-tissue infections (SSTI): a literature review and consensus statement on behalf of the Italian Society of Infectious Diseases and International Society of Chemotherapy.

Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges and resulting in significant morbidity and mortality among patients as well as increased healthcare costs. eight members of the SSTI working group of the Italian Society of infectious Diseases prepared a draft of the statements, grading the quality of each piece of evidence after a careful review of the current literature using MEDLINE database and their own clinical experience. Statements were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America (IDSA). The manuscript was successively reviewed by seven members of the SSTI working group of the international Society of Chemotherapy, and ultimately re-formulated by all e xperts. the microbiological and clinical aspects together with diagnostic features were considered for uncomplicated and complicated SSTIs. Antimicrobial therapy was considered as well -both empirical and targeted to methicillin-resistant Staphylococcus aureus (MRSA) and/or other main pathogens.

Empirical therapy for serious Gram-positive infections: making the right choice.

It is well established that delaying the administration of effective antimicrobials for the treatment of serious infections has a significant impact on patient outcomes. In this atmosphere of urgency, decision-making regarding therapy is further complicated by the current high rates of drug resistance among important pathogens, such as Staphylococcus aureus. To improve treatment outcomes, decrease the risk of mortality and reduce hospital costs, physicians should always administer the most appropriate antimicrobial for the given scenario. When a staphylococcal infection is suspected but the resistance phenotype is not known, agents that are effective against methicillin-susceptible S. aureus and methicillin-resistant S. aureus provide optimal empirical coverage. However, the number of such empirical monotherapeutic options is limited. Daptomycin has proven clinical efficacy as compared with comparator agents in Gram-positive infections, and could be considered an appropriate therapy for the treatment of infections caused by either methicillin-susceptible S. aureus or methicillin-resistant S. aureus.

Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy of enzymes associated with bradykinin-mediated angioedema.

BACKGROUND AND PURPOSE: Inhibition of bradykinin metabolizing enzymes (BMEs) can cause acute angioedema, as demonstrated in a recent clinical trial in patients administered the antihypertensive, omapatrilat. However, the relative contribution of specific BMEs to this effect is unclear and confounded by the lack of a predictive pre-clinical model of angioedema. EXPERIMENTAL APPROACH: Rats were instrumented to record blood pressure and heart rate; inhibitors were infused for 35 min and bradykinin was infused during the last 5 min to elicit hypotension, as a functional marker of circulating bradykinin and relative angioedema risk. KEY RESULTS: In the presence of omapatrilat bradykinin produced dose-dependent hypotension, an effect abolished by B(2) blockade. In the presence of lisinopril (ACE inhibitor), but not candoxatril (NEP inhibitor) or apstatin (APP inhibitor), bradykinin also elicited hypotension. Lisinopril-mediated hypotension was unchanged with concomitant blockade of NEP or NEP/DPPIV (candoxatril+A-899301). However, hypotension was enhanced upon concomitant blockade of APP and further intensified in the presence of NEP inhibition to values not different from omapatrilat alone. CONCLUSIONS AND IMPLICATIONS: We demonstrated that bradykinin is degraded in vivo with an enzyme rank-efficacy of ACE>APP>>NEP or DPPIV. These results suggest the effects of omapatrilat are mediated by inhibition of three BMEs, ACE/APP/NEP. However, dual inhibition of ACE/NEP or ACE/NEP/DPPIV elicits no increased risk of angioedema compared to ACE inhibition alone. Thus, novel BME inhibitors must display no activity against APP to avoid angioedema risk due to high prevalence of ACE inhibitor therapy in patients with diabetes and cardiovascular disease.

Impact of a fluoroquinolone formulary change on acquisition of quinolone-resistant gram-negative bacilli.

Rising rates of fluoroquinolone resistance in bacteria have been associated with increased fluoroquinolone use. In vitro data show differences in potency among fluoroquinolone antibiotics against gram-negative bacteria and have led to the hypothesis that rates of selection of resistant microorganisms may be affected by the choice of the specific fluoroquinolone. Because clinical data to prove this hypothesis are lacking, the aim of the present study was to determine rates of acquisition of quinolone-resistant gram-negative bacilli (QRGNB) in the fecal flora of medical intensive care unit patients before and after a formulary change from ciprofloxacin to levofloxacin. Unadjusted rate ratios for acquisition of QRGNB were 1.09 (95%CI, 1.02-1.16) for each day of ciprofloxacin use and 1.01 (95%CI, 0.87-1.17) for each day of levofloxacin use. Following adjustment for other antibiotic use, enteral feeding, APACHE II score, and nursing home admission, neither ciprofloxacin nor levofloxacin use was associated with acquisition of QRGNB. In conclusion, a formulary change from ciprofloxacin to levofloxacin was not significantly associated with an increased risk of acquisition of QRGNB.

Efficacy of current agents used in the treatment of Gram-positive infections and the consequences of resistance.

The proportion of pathogens causing hospital-onset infections that are resistant to antimicrobial agents continues to increase worldwide. Inadequate antimicrobial therapy is an important factor in the emergence of resistance and is associated with increased mortality. In the USA in 2000, the National Nosocomial Infections Surveillance system reported that >50% of Staphylococcus aureus isolates collected from intensive care units were resistant to methicillin (MRSA). The emergence of community-acquired MRSA is a new concern. MRSA are associated with adverse clinical outcomes and increased hospital costs. The increasing prevalence of MRSA contributes to the use of glycopeptides; however, isolates with intermediate and full resistance to vancomycin and teicoplanin are now being reported. Newer agents, such as the oxazolidinone linezolid, are effective in the treatment of serious Gram-positive infections; however, linezolid-resistant isolates of Enterococcus faecium, Enterococcus faecalis and S. aureus have been reported. Therefore, there is an unmet clinical need for new agents with activity against Gram-positive pathogens. Daptomycin, a lipopeptide with a novel mode of action, was recently approved for the treatment of skin and soft tissue infections in the USA. The two case studies presented herein detail experience with the use of daptomycin in the USA.

Progressive disseminated histoplasmosis presenting as cellulitis in a renal transplant recipient.

With the advent of potent immunosuppressive therapies used in solid organ transplantation, patients are more susceptible to a variety of infectious organisms. Infections may result from atypical pathogens and present in an unusual manner. We describe a case of progressive disseminated histoplasmosis presenting as cellulitis in a renal transplant recipient and review this disease.

Outbreak of adenovirus genome type 7d2 infection in a pediatric chronic-care facility and tertiary-care hospital.

An outbreak of adenovirus infection that involved residents of a pediatric chronic-care facility, staff of a tertiary-care hospital, and a nosocomial hospital case was studied. In the pediatric facility, 31 (33%) of 93 residents had adenovirus infection, and 8 died. Risk factors for illness were an age of < 7 years (P = .004), presence of a tracheostomy (P = .015), and residence on a particular floor (P < .001). In the tertiary-care hospital, 36 health care workers had adenovirus infection; 26 (72%) had failed to follow strict contact and droplet precautions, and 30 (83%) continued to care for patients while they had symptoms. A 5-month-old patient with underlying lung disease acquired severe adenovirus infection in this hospital. All isolates were adenovirus type 7 (Ad7). DNA restriction analysis revealed the band patterns of all isolates to be identical and characteristic of the genome type d2. Thus, Ad7d2 caused significant morbidity and mortality in persons in the pediatric chronic-care facility and tertiary-care hospital. This is the first published description of Ad7d2 strains in the United States.

Effect of novel motilide ABT-229 versus erythromycin and cisapride on gastric emptying in dogs.

ABT-229 (8,9-anhydro-4"-deoxy-3'-N-desmethyl-3'-N-ethylerythromycin B-6,9-hemiacetal), a synthetic derivative of erythromycin (ERY) with no antibiotic activity, has been shown to bind to motilin receptors and stimulate contractile activity of the antrum and small intestine. The objective of this study was to determine the effect of ABT-229 on canine gastric emptying (GE) and contractile activity of the antrum and duodenum in response to a solid meal. Six beagles were used to determine GE of a solid meal and contractile activity in response to either vehicle, ABT-229 (0.17, 0.83, 2.5, or 5.0 microg/kg/min), ERY (33.3 microg/kg/min), or cisapride (CIS) (10 microg/kg/min). Lag (t(lag)), half-emptying (t(1/2)), and complete emptying (t(full)) times were determined. Contractile data were analyzed for motility index and gastroduodenal coordination. Compared with vehicle, ABT-229 dose dependently accelerated GE, t(lag) was decreased at the two highest doses, t(1/2) was decreased compared with vehicle at the three highest doses, and t(full) was decreased at all doses compared with vehicle. ERY also decreased t(1/2) and t(full), whereas CIS decreased all GE parameters. The slopes of the linear phase of GE curves for all drugs and doses were greater than those for vehicle. ABT-229 dose dependently increased the motility index as well as gastroduodenal coordination. ABT-229 (two highest doses) and CIS accelerated GE of a solid meal by decreasing the lag phase and increasing the rate of GE, whereas ERY only increased the rate of GE. The data suggest that ABT-229 is 7- to 40-fold more potent than ERY in accelerating GE.

Is antibiotic prophylaxis necessary for preventing prosthetic device infection?

Preventing bacteremia in patients with implanted prostheses is a logical concern, but whether the danger of infection is real, and whether people actually benefit from antibiotic prophylaxis for dental procedures is not clear. This article examines and discusses currently available data concerning the use of antibiotic prophylaxis to prevent infection associated with prosthetic devices.

Infectious diarrhea.

Infectious diarrhea is an extremely common illness that affects millions of Americans annually. For most patients, the illness is a self-limited one. Its major risk is dehydration. However, for some patients, diarrhea can lead to severe dehydration or be associated with bacteremia and metastatic infection. Patients with these conditions require prompt treatment. A large number of organisms have been associated with diarrhea in humans, and most laboratories routinely screen for Salmonella, Shigella, and Campylobacter. Other bacteria, parasites, and viruses account for a significant percentage of diarrhea cases and frequently go undetected. This article summarizes many of these pathogens and describes the settings in which they can be acquired. Food distribution networks have made the delivery of previously rare foods to remote areas a commonplace occurrence; this has also led to new challenges in the diagnosis and prevention of food-borne illnesses. Outbreaks of diarrhea now frequently extend across many states. The identification of a rare strain of a bacterial pathogen or changes in the isolation rate of common pathogens may be early clues to the cause of such an ongoing outbreak. Most enteric pathogens cause disease by either stimulating the secretion of fluids at the level of the small bowel or by irritating and invading the colon. Organisms that cause disease by the latter mechanism have the potential to invade the blood stream and spread to other parts of the body, including the bones and the central nervous system. Several organisms have been associated with specific postinfectious syndromes that are responsible for additional morbidity and mortality. The antibiotic resistance of bacterial pathogens has been increasing, and this has a limiting effect on the empiric treatment choices available for suspected bacterial diarrhea. Careful attention to local sensitivity patterns and appropriate testing of the patient's isolate are among the important factors that lead to successful treatment decisions.

Infective Endocarditis.

Infective endocarditis remains a serious and potentially fatal disease. Even with appropriate therapy, mortality rates remain at about 10% to 20%. Common errors in treatment include starting antibiotics before obtaining at least three blood cultures, failing to use bactericidal drugs, stopping therapy too early, and delaying heart surgery when it is indicated. The epidemiology of endocarditis will continue to evolve, and we will see more cases that are hospital acquired, more cases associated with the presence of cardiac support devices, and cases associated with line-related bacteremia. Therefore, organisms associated with endocarditis will also likely evolve. We will see more cases due to multiresistant organisms (eg, vancomycin-resistant enterococci, glycopeptide-resistant staphylococci, and multidrug-resistant gram-negative rods) as well as yeast and fungi.

Prolonged suppressive antibiotic therapy for infected orthopedic prostheses.

Prolonged suppressive antibiotic therapy may be an alternative to removal of infected orthopedic prostheses in some patients. However, the efficacy of prolonged suppressive antibiotics is not well established. We retrospectively reviewed 18 patients with infected orthopedic prostheses who had been treated with prolonged antimicrobial suppression during the last 10 years. Eighteen episodes of infection were identified in these 18 patients. There were nine men and nine women, and the mean age was 66 years (range, 31-83 years). All patients had a functional prosthesis and were treated with surgical debridement, retention of the prosthesis, and administration of intravenous antibiotics for 6-8 weeks, followed by prolonged oral antibiotic suppression. Fifteen of the 18 patients appear to have had a good response and have been able to retain a functional prosthesis. Complications related to antibiotic suppression occurred in 22% but did not necessitate discontinuation of the antibiotic therapy. Prolonged antibiotic suppression is a reasonable alternative to surgery in selected patients with infected orthopedic prostheses.

A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia.

Five hundred ninety patients were enrolled in a prospective, multicenter, randomized trial comparing the efficacy and safety of 7 to 14 days of levofloxacin treatment with that of ceftriaxone and/or cefuroxime axetil in the management of community-acquired pneumonia in adults. Patients received either intravenous and/or oral levofloxacin (500 mg once daily) or the comparative agents, parenteral ceftriaxone (1 to 2 g once to twice daily) and/or oral cefuroxime axetil (500 mg twice daily). Erythromycin or doxycycline could be added to the comparator arm at the investigator's discretion. The decision to use an intravenous or oral antimicrobial agent for initial therapy was made by the investigator. Clinical and microbiological evaluations were completed at the baseline, during treatment, 5 to 7 days posttherapy, and 3 to 4 weeks posttherapy. Four hundred fifty-six patients (226 given levofloxacin and 230 administered ceftriaxone and/or cefuroxime axetil) were evaluable for clinical efficacy. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 15 and 12%, respectively, of clinically evaluable patients. One hundred fifty atypical pathogens were identified: 101 were Chlamydia pneumoniae, 41 were Mycoplasma pneumoniae, and 8 were Legionella pneumophila. Clinical success at 5 to 7 days posttherapy was superior for the levofloxacin group (96%) compared with the ceftriaxone and/or cefuroxime axetil group (90%) (95% confidence interval [CI] of -10.7 to -1.3). Among patients with typical respiratory pathogens who were evaluable for microbiological efficacy, the overall bacteriologic eradication rates were superior for levofloxacin (98%) compared with the ceftriaxone and/or cefuroxime axetil group (85%) (95% CI of -21.6 to -4.8). Levofloxacin eradicated 100% of the most frequently reported respiratory pathogens (i.e., H. influenzae and S. pneumoniae) and provided a >98% clinical success rate in patients with atypical pathogens. Both levofloxacin and ceftriaxone-cefuroxime axetil eradicated 100% of the S. pneumoniae cells detected in blood culture. Drug-related adverse events were reported in 5.8% of patients receiving levofloxacin and in 8.5% of patients administered ceftriaxone and/or cefuroxime axetil. Gastrointestinal and central and peripheral nervous system adverse events were the most common events reported in each treatment group. In conclusion, these results demonstrate that treatment with levofloxacin is superior to ceftriaxone and/or cefuroxime axetil therapy in the management of community-acquired pneumonia in adults.

Defect in interleukin-1beta secretion prevents sickness behavior in C3H/HeJ mice.

To examine the role of interleukin-1beta (IL-1beta) in mediating sickness, we studied the effects of lipopolysaccharide (LPS) and IL-1beta on social behavior in endotoxin-responsive C3H/HeOuJ (OuJ) mice and endotoxin-resistant C3H/HeJ (HeJ) mice. Whereas LPS (1, 10 and 100 microg) depressed social behavior and body weight compared to saline in OuJ mice, in HeJ mice it did not. To determine if the refractoriness of HeJ mice to the behavioral effects of LPS was related to secretion of IL-1beta, in a second study, HeJ and OuJ mice were injected IP with LPS (10 microg) and plasma concentration of IL-1beta was determined postinjection. At 4 h postinjection, the plasma concentration of IL-1beta was increased by LPS in OuJ mice, but not in HeJ mice. The increase in plasma IL-1beta in OuJ mice corresponded to the maximal depression in social behavior. To further verify that HeJ mice are refractory to the behavioral effects of LPS because they fail to respond and produce cytokines, the social behavior of HeJ and OuJ mice injected IP with recombinant murine IL-1beta (0, 50, 100, or 200 ng) was compared. As anticipated, exogenous IL-1beta depressed social behavior similarly in endotoxin-responsive OuJ mice and endotoxin-resistant HeJ mice. These data indicate that a genetic mutation in HeJ mice that prevents LPS-induced synthesis of cytokines also renders HeJ mice refractory to the behavioral effects of LPS.

Choosing the right macrolide antibiotic. A guide to selection.

Macrolide antibiotics have proven to be valuable alternatives to penicillins and cephalosporins for the treatment of a number of infections. Currently, a number of macrolides are available. When choosing a particular macrolide, the types of organisms causing the infection, the tolerability of the drug, convenience of dosing and possible drug interactions all must be taken into account. Erythromycin, azithromycin and clarithromycin are equally effective against most gram-positive organisms. However, clarithromycin and azithromycin have much better activity against Haemophilus influenza and Moraxella catarrhalis. Thus, these 2 drugs are better choices for the treatment of community-acquired pneumonia. However, the low serum concentrations of azithromycin may be a problem in patients with bacteraemia associated with with community-acquired pneumonia. Clarithromycin appears to be effective for the treatment and prophylaxis of Mycobacterium avium complex (MAC) in patients with AIDS, while azithromycin appears to be effective for prophylaxis. Treatment of MAC with azithromycin is currently undergoing study. Although clarithromycin is the macrolide of choice for the treatment of Helicobacter pylori, azithromycin is the preferred macrolide for the treatment of Chlamydia trachomatis infections. The major factor limiting the use of azithromycin and clarithromycin has been their cost. However, these drugs may be cost effective if compliance is improved due to better tolerability and more convenient dosing regimens.

Acute bacterial meningitis.

Despite improvements in antibiotic therapy and the use of vaccines and chemoprophylaxis, acute bacterial meningitis remains a significant cause of morbidity and mortality in the United States. Early diagnosis and therapy are important once the condition has been considered and the appropriate available specimens collected. Changes in epidemiologic frequencies and antimicrobial susceptibilities suggest that therapy will become more uniform across all age groups. Rapid, specific diagnostic modalities for all etiologic agents and improved vaccines for Neisseria meningitidis type B and Streptococcus pneumoniae are urgently needed.

In vitro activity of macrolides against intracellular Legionella pneumophila.

The antibacterial effects of clarithromycin, azithromycin, and erythromycin were determined against five strains of Legionella pneumophila including L. pneumophila ATCC 33823 and four clinical isolates. Extracellular minimum inhibitory concentrations (MICs) and MBCs were determined by a microdilution method. Clarithromycin was the most active drug (MIC < or = 0.015-0.06), followed by azithromycin (MIC 0.03-0.12) and erythromycin (MIC 0.06-0.25). The antibacterial effect of these macrolides was then determined against L. pneumophila grown intracellularly in MRC-5 human fetal lung fibroblast cells. At two and eight times the extracellular MBC, erythromycin, azithromycin, and clarithromycin were equally effective in inhibiting growth of these five strains of intracellular L. pneumophila.

Bacteriologic and clinical applications of a new extended-spectrum parenteral cephalosporin.

Although third-generation cephalosporins have been considered the backbone of antibiotic therapy for the treatment of many kinds of serious infections, including those in hospitalized patients, lack of activity against some important pathogens still exists among currently available drugs. In addition, increasing accounts of antibiotic resistance, particularly in the hospital environment, are of deep concern and have thus led to the need for the development of newer antimicrobial agents. Cefepime is a now parenteral cephalosporin with an extended spectrum of antibacterial activity that includes both aerobic gram-negative and gram-positive bacteria. It is also active against many gram-negative organisms resistant to ceftriaxone and cefotaxime, as well as many strains of Enterobacter and Citrobacter resistant to ceftazidime. Cefepime appears to be less likely to select out resistant organisms, and it may be less likely to change hospital flora than currently available antimicrobials. Cefepime has been shown to be very well tolerated and effective in the treatment of a variety of infections including moderate-to-severe pneumonia (including cases associated with concurrent bacteremia), complicated and uncomplicated urinary tract infections (also including cases associated with concurrent bacteremia), and skin and skin-structure infections. Clinical response rates are > or = 75% for most infections and have been comparable to ceftazidime in comparative trials. In addition, pretreatment susceptibility testing indicates that >94% of organisms isolated in patients enrolled in clinical trials were susceptible to cefepime.

Antibiotic therapy in the allergic patient.

A variety of antimicrobial classes are now available. Thus, a careful history and skin testing for hypersensitivity reactions are often not done. It is often easier to give an alternative agent rather than to determine if the person does indeed have a hypersensitivity reaction to a particular drug. There remain situations (e.g., enterococcal endocarditis, neurosyphilis, syphilis in pregnant women), however, in which options for appropriate therapy are limited. In this setting, an accurate history accompanied by appropriate skin testing and desensitization is indicated.