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Acridine-a neglected antibacterial chromophore.

The use of acridines as antimicrobial agents was first proposed by Ehrlich and Benda in 1912, and the first clinical use of these agents occurred in 1917. Many compounds containing the acridine chromophore were synthesized and tested, and the aminoacridines found wide use, both as antibacterial agents and as antimalarials, during World War II. The emergence of the penicillins eclipsed the acridines in antisepsis due to the greater therapeutic efficacies of the former. However, with the current massive increases in drug-resistant bacterial infection, new acridine derivatives may be of use. In addition, the topical utilization of aminoacridines in conjunction with directed low-power light offers bactericidal action at much lower doses.

Aminoacridines↗

Povidone iodine and skin disinfection before initiation of epidural anesthesia.

BACKGROUND: Povidone iodine (PI) solution is used commonly for skin disinfection before epidural and spinal anesthesia. Although there have been reports indicating the presence of microbial contaminants in PI solution, none have evaluated the prevalence of PI contamination. The aims of this study were to assess the frequency of bacterial contamination of previously opened bottles of PI solution and to compare the effectiveness of new and previously opened bottles of PI solution for skin disinfection. METHODS: Twenty previously opened and ten previously unopened multiple-use bottles of PI solution were evaluated for microbial contamination. In addition, final swabs and PI solution used for skin disinfection in 80 patients undergoing elective epidural analgesia were evaluated. RESULTS: The inside of the bottle cap or the PI solution from 40% of the multiple-use PI bottles in use were contaminated. There was no growth from any previously unused PI bottles. Povidone iodine from newly opened bottles provided more effective skin decontamination than did solution from previously opened bottles. CONCLUSIONS: Multiple-use PI bottles in normal use may become contaminated by bacteria. In addition, PI solution from previously opened bottles was less effective than PI from previously unopened bottles. Based on these findings, if PI solution is chosen for skin antisepsis before initiation of epidural and spinal anesthesia, only single-use containers should be used.

Anesthesia, Epidural↗

Chlorhexidine versus povidone iodine in preventing colonization of continuous epidural catheters in children: a randomized, controlled trial.

BACKGROUND: Chlorhexidine is better than povidone iodine for skin preparation before intravascular device insertion or blood culture collection, but it is not known whether chlorhexidine is superior in reducing colonization of continuous epidural catheters. METHODS: Children requiring an epidural catheter for postoperative analgesia longer than 24 h were randomly assigned to receive skin preparation with an alcoholic solution of 0.5% chlorhexidine or an aqueous solution of 10% povidone iodine before catheter insertion. Using surgical aseptic techniques, catheters were inserted into either the lumbar or the thoracic epidural space based on the preferences of the anesthesia team, on clinical indication, or both. Immediately before epidural catheter removal, their insertion site and hub were qualitatively cultures. After their removal, the catheter tips were quantitatively cultured. Catheters were classified as colonized when their tips yielded 1,000 or more colony-forming units/ml in cultures. RESULTS: Of 100 randomly assigned patients, 96 were evaluable. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters were kept in place for a median (range) duration of 50 (range, 21-100) h. Catheters inserted after skin preparation with chlorhexidine were one sixth as likely and less quickly to be colonized as catheters inserted after skin preparation with povidone iodine (1 of 52 catheters [0.9 per 100 catheter days] vs. 5 of 44 catheters [5.6 per 100 catheter days]; relative risk, 0.2 [95% confidence interval, 0.1-1.0]; P = 0.02). Coagulase-negative staphylococci were the only colonizing microorganisms recovered, and the skin surrounding the catheter insertion site was the origin of all the colonizing microorganisms. CONCLUSIONS: Compared with aqueous povidone iodine, the use of alcoholic chlorhexidine for cutaneous antisepsis before epidural catheter insertion reduces the risk of catheter colonization in children.

Adolescent↗

Reduction of colonization and infection rate during pediatric intensive care by selective decontamination of the digestive tract.

OBJECTIVE: To compare the effects of two different antibiotic regimes on the colonization and infection rates of critically ill pediatric patients. DESIGN: A prospective randomized trial. SETTING: A pediatric ICU in a university hospital. PATIENTS: Fifty critically ill pediatric patients who required intensive care for at least 4 days were randomly allocated to either the selective parenteral and enteral antisepsis regimen (treatment group, n = 25) or the control group (n = 25). INTERVENTIONS: The treatment group received oral nonabsorbable antimicrobial agents (polymyxin E, gentamicin, and amphotericin B) and parenteral cefotaxime, whereas the control group received either perioperative antibiotic prophylaxis or antibiotic therapy according to clinical or microbiological evidence of infection. RESULTS: Both groups were comparable for age, body weight, sex, and severity of illness. Colonization with Gram-negative microorganisms and yeasts in the oropharynx, and digestive and respiratory tracts increased rapidly up to 52% in the control group, whereas there was no colonization with these microorganisms in the treatment group. The occurrence rates of acquired secondary infections in the control and treatment groups were 36% and 8%, respectively (p less than .025). There were no differences between groups in the duration of intensive care or mortality rate. CONCLUSION: Selective oropharyngeal and gastrointestinal decontamination combined with systemic cefotaxime application allows for a significant reduction of the colonization rate with Gram-negative bacteria and yeasts in critically ill pediatric patients undergoing prolonged intensive care. In addition, it significantly reduces the Gram-negative infection rate of the respiratory system. However, this therapeutic approach does not alter ICU length of stay or mortality rate.

Anti-Bacterial Agents↗

Postsurgical prevertebral abscess of the cervical spine.

OBJECTIVES: Prevertebral abscess formation is an uncommon occurrence following cervical spine fusion surgery. Abscesses may present early or in a delayed fashion and require surgical drainage and long-term antibiotic treatment. The issues of osteomyelitis and the need for plate removal remain unresolved. STUDY DESIGN: A case series of six tetraplegic patients admitted for rehabilitation to the Chaim Sheba Medical Center (Tel Hashomer, Israel) is presented. METHODS: Five patients were trauma patients; one patient underwent repeated procedures and irradiation for tumor of the cervical spine. All patients developed prevertebral abscesses after a mean period of 30 days from their fusion surgery. Computed tomography scan was used in all patients to establish the diagnosis and define the extent of the infective process. All patients underwent one or more drainage procedures. The plate was removed in two patients at 1 and 4 months. RESULTS: Infection completely resolved in four patient and was refractory in one patient with malignant tumor, and a chronic small fistula remained in one case. Staphylococcus aureus was the main infective organism, but mixed infections were the rule. Even for a protracted course of infection, no significant osteomyelitis was encountered. CONCLUSIONS: Abscess formation after instrumentation of the neck may be more common than formerly recognized. Despite the prolonged course of disease and treatment, osteomyelitis is not a major concern. There is no automatic indication for plate removal to control infection, although plating may be safely removed after 10 to 12 weeks if the neck is explored and the cervical spine is stable. A high index of suspicion is warranted, and early recognition and diagnosis, prompt surgical drainage under general anesthesia, and long-term antibiotic treatment are key for eradication of the infective process. Prophylactic antibiotics may be of value. Meticulous antisepsis and surgical technique should be maintained to reduce the incidence of these severe complications.

Abscess↗

A review of risk factors for catheter-related bloodstream infection caused by percutaneously inserted, noncuffed central venous catheters: implications for preventive strategies.

Strategies for preventing central venous catheter (CVC)-related bloodstream infection are most likely to be effective if guided by an understanding of the risk factors associated with these infections. In this critical review of published studies of risk factors for CVC-related bloodstream infection that were prospective and used multivariable techniques of data analysis or that were randomized trials of a preventive measure, a significantly increased risk of catheter-related bloodstream infection was associated with inexperience of the operator and nurse-to-patient ratio in the intensive care unit, catheter insertion with less than maximal sterile barriers, placement of a CVC in the internal jugular or femoral vein rather than subclavian vein, placement in an old site by guidewire exchange, heavy colonization of the insertion site or contamination of a catheter hub, and duration of CVC placement > 7 days. Prospective studies or randomized trials of control measures focusing on these risk factors have been shown to reduce risk significantly: formal training in CVC insertion and care, use of maximal sterile barriers at insertion, use of chlorhexidine rather than povidone-iodine for cutaneous antisepsis, applying a topical anti-infective cream or ointment or a chlorhexidine-impregnated dressing to the insertion site, and the use of novel catheters with an anti-infective surface or a contamination resistant hub. Better prospective studies of sufficient size to address all potential risk factors, including insertion site and hub colonization, insertion technique, and details of follow-up care, would enhance our understanding of the pathogenesis of CVC-related bloodstream infection and guide efforts to develop more effective strategies for prevention.

Asepsis↗

The genesis of neurosurgery and the evolution of the neurosurgical operative environment: part I-prehistory to 2003.

Despite its singular importance, little attention has been given to the neurosurgical operative environment in the scientific and medical literature. This article focuses attention on the development of neurosurgery and the parallel emergence of its operative setting. The operative environment has, to a large extent, defined the "state of the art and science" of neurosurgery, which is now undergoing rapid reinvention. During the course of its initial invention, major milestones in the development of neurosurgery have included the definition of anatomy, consolidation of a scientific basis, and incorporation of the practicalities of anesthesia and antisepsis and later operative technical adjuvants for further refinement of action and minimalism. The progress, previously long and laborious in emergence, is currently undergoing rapid evolution. Throughout its evolution, the discipline has assimilated the most effective tools of modernity into the operative environment, leading eventually to the entity known as the operating room. In the decades leading to the present, progressive minimalization of manipulation and the emergence of more refined operative definition with increasing precision are evident, with concurrent miniaturization of attendant computerized support systems, sensors, robotic interfaces, and imaging devices. These developments over time have led to the invention of neurosurgery and the establishment of the current state-of-the-art neurosurgical operating room as we understand it, and indeed, to a broader definition of the entity itself. To remain current, each neurosurgeon should periodically reconsider his or her personal operative environment and its functional design with reference to modernity of practice as currently defined.

History, 15th Century↗

Lack of evidence of efficacy of cohorting nursing personnel in a neonatal intensive care unit to prevent contact spread of bacteria: an experimental study.

Nurse cohorting was investigated in a modern neonatal intensive care unit (NICU). During 99 days bacterial infection and colonization rates were determined in 100 infants experimentally assigned cohort or noncohorted care. Colonizing isolate identity was determined by plasmid profile analyses and biotyping in weekly surveillance cultures. Between Days 2 and 7, 3 infections occurred in cohorted infants but none in noncohorted ones. No secondary spread of infection or definitive colonization cluster occurred. The first colonization rate, at any site, was 0.53/patient-week in the noncohorted and 0.3 to 0.4 in the cohorted units (P greater than 0.05). Colonization ratios with species other than usual skin bacteria in the respiratory tract and with species other than Escherichia coli in the rectum were lower for noncohorted infants. Effective infection control practices in a modern NICU, including alcohol hand antisepsis, should obviate a need for cohorting.

Bacterial Infections↗

Use of antimicrobials to prevent postoperative infection in patients with cataracts.

Despite the high frequency of cataract surgery, there are still no definitive studies on antibiotic prophylaxis against endophthalmitis after cataract surgery. Most surgeons follow an empiric approach. The results of several recent studies shed additional light on this complex topic. There is better knowledge of the usual source of the infection and the specific organisms incriminated. This review presents some principles of prophylactic treatment and selected literature that addresses the effectiveness of antisepsis, topical preoperative antibiotics, intracameral antibiotics, subconjunctival antibiotics, systemic antibiotics, and postoperative antibiotics. The worldwide problem of antibiotic resistance should temper our approach. Some organizational statements are reviewed, and personal recommendations are offered. Controversy still abounds.

Anti-Infective Agents↗

Is umbilical flora responsible for wound infection after laparoscopic surgery?

To our knowledge, the association of umbilical flora and infections has not been studied yet. The aim of this study was to identify the causative agents for trocar site infections and to highlight whether there is association between umbilical flora and trocar site infections. One hundred consecutive patients who had undergone laparoscopic surgery were studied. Microbiological samples were taken from the umbilicus before (group 1) and after (group 2) antisepsis with povidone-iodine. Microbiological assessment was done for wounds suspected to be infected, and the wounds with positive cultures were classified as group 3. The incidence of wound infection was 8%. One hundred percent of the infections were associated with the extraction trocar. Eighty-nine percent of all of the infections occurred after laparoscopic cholecystectomy, whereas 11% occurred after laparoscopic appendectomy. The micro-organisms in group 3 did not belong to the skin flora, unlike the micro-organisms in groups 1 and 2, but hospital-acquired pathogens were responsible for the infections. The umbilical flora and the bile are not the source of the surgical site infections after laparoscopic surgery in our study despite the considerations in the literature.

Adult↗

Alcoholic povidone-iodine to prevent central venous catheter colonization: A randomized unit-crossover study.

OBJECTIVE: To compare effectiveness in preventing central venous catheter colonization and infection of two protocols of cutaneous antisepsis using povidone-iodine solution in combination with ethanol or water. DESIGN: Randomized trial. SETTING: Medical intensive care department in a university hospital. PATIENTS: Consecutive patients requiring central venous catheter in two similar 11-bed units from January 1, 2001, to January 1, 2002. INTERVENTIONS: Alcoholic povidone-iodine solution protocol was randomly assigned to one of two units when the study began. Every 3 months the alcoholic protocol was switched from one unit to the other. Depending on the unit and the time the patient was admitted, catheters were inserted and cared for with 10% aqueous povidone-iodine solution or 5% povidone-iodine solution 70% ethanol-based combination. MEASUREMENTS AND MAIN RESULTS: Rates of catheter colonization, catheter-related bacteremia, and catheter-related infection were compared in the two protocols; 223 catheters were included in an intent-to-treat analysis. The incidence of catheter colonization was significantly lower in the alcoholic povidone-iodine solution protocol than in the aqueous povidone-iodine solution protocol (relative risk, 0.38; 95% confidence interval, 0.22-0.65, p <.001), and so was the incidence of catheter-related infection (relative risk, 0.34; 95% confidence interval, 0.13-0.91, p <.04). Catheter-related bacteremia were similar in both protocols. After adjusting for other risk factors, time to central venous catheter colonization was significantly longer in the alcoholic solution (adjusted hazards ratio, 0.3; 95% confidence interval, 0.2-0.6, p <.001). Based on a subgroup of 114 patients (57 in each protocol), analysis of 57 pairs of central venous catheters matched for age, duration, and site of insertion found similar results regarding the superiority of alcoholic povidone-iodine solution in preventing central venous catheter colonization and infection. CONCLUSIONS: The use of alcoholic povidone-iodine for skin disinfection reduced the incidence of catheter colonization and related infection compared with aqueous 10% povidone-iodine disinfection in an adult intensive care unit.

Anti-Infective Agents, Local↗

Endpoints in sepsis trials: more than just 28-day mortality?

To determine whether an intervention, either therapeutic or diagnostic, is effective, it needs to be assessed according to a predefined endpoint (or outcome measure), the choice of which will vary according to the aims of the study in question and the anticipated effects of the intervention being tested. Studies can have one of several functions (which are not always mutually exclusive), including providing evidence of biological efficacy, determining a clinically important benefit, and achieving regulatory approval. In trials of therapeutic efficacy in sepsis, mortality rates are a good endpoint because death is common and mortality rates are an unambiguous measure: patients either survive or they do not. However, the time at which mortality should be recorded is less clear cut, and this single endpoint provides no information regarding the biological activity or disease modification effects of the agent under investigation. In this article, we will briefly discuss some of the potential alternative endpoints that could be used in the assessment of antisepsis agents.

Clinical Trials as Topic↗

No need for preoperative antiseptics in elective outpatient plastic surgical operations: a prospective study.

The development of antisepsis in the late nineteenth and early twentieth centuries revolutionized health care. The time-honored technique of skin preparation is to scrub the entire operative area of the patient for 5 to 7 minutes with a germicidal detergent solution and then paint the region with an antimicrobial solution of either tincture of povidone-iodine (Betadine) or chlorhexidine. Although antiseptics result in lower colony counts on the skin, they have side effects and higher cost in relation to normal saline. The authors have prepared patients by showering the surgical site with soap and water and rinsing it with normal saline, in 905 cases of outpatient, clean-wound plastic surgery. In another 905 cases that served as the control group, the traditional method of preoperative shower and scrub with chlorhexidine or Betadine was used. In both groups, there was no incidence of wound infection.

Adult↗

Ephraim McDowell: the qualities of a good surgeon.

OBJECTIVE: To identify those personal qualities which enabled Dr. Ephraim McDowell to be successful as the first surgeon in the world to remove a large ovarian tumor. SUMMARY BACKGROUND DATA: Dr. McDowell, in 1809 and before anesthesia or antisepsis, removed a large ovarian tumor from his patient, Jane Todd Crawford, who then survived 33 years. METHODS: Existing histories and accounts of Ephraim McDowell's life and operations were sifted for his personal qualities. A visit to the McDowell House and family 200 reunion in Danville, Kentucky, added details. RESULTS: Qualities of confidence, compassion, courage, commitment, communication, courtesy, and especially cleanliness have been identified. CONCLUSIONS: Those qualities attributed to Ephraim McDowell perhaps were instrumental in his successes. Those basic qualities are still important for surgeons today.

Female↗

Centennial review of corneal transplantation.

Abstract One hundred years ago, on 7 December 1905, Dr Eduard Zirm performed the world's first successful human corneal transplant. This significant milestone was achieved only after many decades of unsuccessful trial and error; however, it did not lead to relatively 'routine' keratoplasty success for several more decades. The idea of replacing an opaque cornea had been suggested for centuries, and had stimulated theoretical approaches to the problem by many esteemed physicians throughout history. However, little practical progress was made in the ultimate realization of the dream until the 19th century when pioneering surgeons pursued extensive studies in relation to both animal and human 'keratoplasty'. Clinical progress and scientific insight developed slowly, and it was ultimately due to parallel advances in medicine such as anaesthesia and antisepsis that Zirm's success was finally achieved. Key concepts were enshrined such as the use of fresh tissue from the same species, careful placement and handling of tissue, and the development of specialized instrumentation such as the circular trephine. In the latter half of the 20th century, many 'masters' of corneal surgery evolved significant refinements in technique and instrumentation with the development of corticosteroids, antibiotics, surgical microscopes, improved trephines, viscoelastics and suture materials, that enable this delicate procedure to be routinely performed with the prospect of success. There are still limitations to corneal transplantation, and corneal allograft rejection still poses the greatest challenge to the modern corneal surgeon. In the foreseeable future it may be in the laboratory, rather than the theatre, that further milestones will be achieved. This review aims to highlight the significant milestones in the rich history of corneal transplantation, and to pay tribute to the many inspired and dedicated individuals involved in the development of keratoplasty to a point where the procedure is now a standard tool in the repertoire of ophthalmic surgery and more than a million people have enjoyed restoration of useful sight.

Corneal Transplantation↗

A view of the development of intestinal suture. Part II. Principles and techniques.

During the 19th century, the principles of suturing and operating upon the bowel were developed. Lembert published his technique, emphasizing the importance of the serosa in 1826. This brought about sudden transition from the ancient methods of intestinal surgery. Considerable controversy followed. Dieffenbach reported the first clinical success with this suture in 1836. Lister introduced aseptic sutures and the principles of antisepsis to the intestine which allowed the subsequent developments. The importance of the submucosa in anchoring a stitch, so that divided surfaces could stay opposed, was drawn to surgeons' attention by Gross and by Halsted. Mall described the histologic changes and pointed out that necrosis would occur if sutures were too close or too tight. More than 200 modifications were described by the beginning of the 20th century. During the 1950s, everting suture was compared with inverting anastomoses, and the safety of this method was realized.

Anastomosis, Surgical↗

Studies of the surgical scrub.

BACKGROUND: To evaluate the effectiveness of various scrub techniques in reducing bacterial skin flora, the present study was developed in three stages. METHODS: Each stage involved fingertip bacterial colony counts measured before, immediately after and 30 min after a variety of handwashing techniques using 10% povidone iodine solution. The first compared 1, 2 or 3 non-timed washes from fingertips to elbows in 10 volunteers. The second compared two volunteers scrubbing for equal durations with or without friction rubbing, while the third involved 15 volunteers who each scrubbed for different time intervals. RESULTS: The first stage showed that a single wash episode failed to provide lasting bacterial colony count reductions on fingertip cultures. The second showed that enduring colony count reductions occur whether friction rubbing of the hands was used or not, and the third showed that a 30 s wash was as effective as washing for longer periods in reducing fingertip flora. CONCLUSIONS: These findings suggest that prolonged vigorous pre-operative scrubbing is unnecessary, although more than a cursory wash is required to produce lasting fingertip antisepsis.

Anti-Infective Agents, Local↗