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Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters.

More than 90% of all intravascular device-related septicaemias are due to central venous or arterial catheters. To assess the efficacy of cutaneous antisepsis to prevent catheter-associated infection, we prospectively studied three antiseptics for disinfection of patients' central venous and arterial catheter insertion sites in a surgical intensive care unit. 668 catheters were randomised to 10% povidone-iodine, 70% alcohol, or 2% aqueous chlorhexidine disinfection of the site before insertion and for site care every other day thereafter. Chlorhexidine was associated with the lowest incidence of local catheter-related infection (2.3 per 100 catheters vs 7.1 and 9.3 for alcohol and povidone-iodine, respectively, p = 0.02) and catheter-related bacteraemia (0.5 vs 2.3 and 2.6). Of the 14 infusion-related bacteraemias (4 due to contaminated infusate or catheter hub, 10 due to infected catheters), 1 was in the chlorhexidine group and 13 were in the other two groups (odds ratio 0.16, p = 0.04). We conclude that use of 2% chlorhexidine, rather than 10% povidone-iodine or 70% alcohol, for cutaneous disinfection before insertion of an intravascular device and for post-insertion site care can substantially reduce the incidence of device-related infection.

1-Propanol↗

Vascular catheter-related sepsis: diagnosis and prevention.

Although catheter-related sepsis (CRS) is an important cause of nosocomial infection and the major complication of intravenous catheter use, there is, as yet, no consensus concerning either a useful definition of CRS or the optimal method of catheter management and prevention of infection. Semiquantitative culture of catheter tips is a useful method of diagnosis of CRS but other techniques such as quantitative catheter blood cultures and Gram staining of the catheter have roles in selected patients. The most significant impact on the prevention of CRS is made by the introduction of an intravenous therapy team. The site and method of catheter insertion, type of dressing and antisepsis, catheter flushing and use of prophylactic antibiotics are also important issues. Techniques such as guide-wire exchange and catheters such as triple lumen and total implantable venous access devices have their own infection problems. Many new and interesting approaches to the prevention of CRS are being formulated. To facilitate further progress, a standardized definition for diagnosis, and revised recommendations for prevention of CRS would be helpful.

Anti-Bacterial Agents↗

A systems approach to preoperative surgical patient skin preparation.

BACKGROUND: The merits of a systems approach to preoperative surgical patient skin preparation are presented. A "system" may be defined as the addition of an antiseptic bath(s) or shower(s) within 24 hours before the application of a Food and Drug Administration-compliant patient preoperative skin preparation at the time of surgery. The expected outcome from this added effort is a further reduction in the transient and normal flora that contaminate the skin surrounding the operative site, and contribute to surgical infections. The Centers for Disease Control and Prevention has recommended the addition of this step to the preoperative site preparation regimen. METHODS: A human in vivo study comparing an alcohol-based (ethanol) system to an iodine-based approach, and 2 sets of clinical observations, are presented here. RESULTS: The data confirm the utility of the systems approach. The in vivo study demonstrates that significant reductions (> or =2 log(10)) in normal and transient flora can be achieved quickly and maintained out to 72 hours after the surgery, allowing for wound closure in a prolonged state of skin antisepsis. Clinical observations support the in vivo findings. After initiation of the system, the infection rates for the monitored procedures have decreased. CONCLUSIONS: The data presented here delineate the merits of a systems approach to preoperative surgical patient skin preparation. This approach has a positive impact on infection rates and may reduce the additional costs associated with this preventable event.

Anti-Infective Agents, Local↗

A unique water optional health care personnel handwash provides antimicrobial persistence and residual effects while decreasing the need for additional products.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) has published guidelines for hand hygiene practices, recommending a handwash regimen that alternates between waterless alcohol products and antimicrobial or nonantimicrobial soap and water. The advent of an alcohol-based product that can be used with or without water (ie, water optional) to decontaminate the hands while providing immediacy of kill and antimicrobial persistence could reduce the confusion associated with handwash guidelines. Such a product has been developed, is alcohol-based (61%), and zinc pyrithione (ZPT) preserved (61% alcohol-ZPT) and has proven to be fully compliant with the Food and Drug Administration (FDA) and CDC guidelines. METHODS: FDA-required testing of the 61% alcohol-ZPT product for the health care personnel handwash indication was performed as outlined in the Tentative Final Monograph (TFM) for Health-Care Antiseptic Drug Products, employing waterless and water-aided product applications. It was next assessed for antimicrobial persistence and residual effects by comparing it, in separate waterless and water-aided applications, with commonly available handwashes containing various antimicrobials in a 5-day study employing 49 subjects, in which samples were collected immediately and at 4 hours and 8 hours postapplication. The skin conditioning properties of this formulation were investigated via appropriate methods. RESULTS: The 61% alcohol-ZPT product easily produced >3.0 log 10 reduction in the indicator strain ( Serratia marcescens ) following the first wash, exceeding the 2.0 log 10 FDA requirement. This level of performance was maintained through the tenth wash, surpassing the 3.0 log 10 FDA requirement for the handwash indication. For the assessment of persistence and residual effect in the waterless mode, the water-optional, 61% alcohol-ZPT product consistently produced log 10 reductions of nearly 3.5 or greater at every point over the entire study period. In the water-aided configuration, similar results were obtained as log 10 reductions of 2.5 were observed. The formulation is nonirritating, actually contributing to hand skin condition. CONCLUSIONS: The 61% alcohol-ZPT product exceeds all FDA criteria for the health care personnel handwash indication and is a significant advancement in the concept of skin antisepsis. It represents a single product suitable for use in all hand hygiene settings, demonstrating improved antimicrobial persistence and residual effects. The 61% alcohol-ZPT formulation contributes positively to overall hand conditioning, and a previously reported study has documented it to be virucidal for several DNA and RNA viruses.

Adolescent↗

[Catheter-related infections: microbiology].

Coagulase negative staphylococci, Staphylococcus aureus and Pseudomonas sp. are the most frequent microorganisms responsible for catheter-related infections. A relative frequency of microorganisms varies according to the countries, microenvironment and outbreaks of multiresistant bacterias. Infections due to fungi, S. aureus and Pseudomonas sp. are associated with the more severe complications. Recent data suggest that chlorhexidine, either used for cutaneous antisepsis or for catheter impregnation decreases infections due to gram positive cocci. Ecological data should be taken into account when deciding a probabilistic treatment in case of suspicion of catheter-related infection.

Anesthesia↗

Infection control: old problems and new challenges.

Infection control faces radical changes at the beginning of the third millennium. The first part of this review focuses on problems not yet solved, such as 1) surveillance systems, which should be active and extremely flexible; 2) infection outbreaks in hospitals and strategies to avoid them; 3) hand washing and alternatives such as rapid hand antisepsis; 4) water and food in the hospital as potential reservoirs of nosocomial pathogens; 5) upgrading of infection control programs to turn them into systems to improve the quality of care; 6) fatal Gram-negative bacteremias in hospitals from developing countries, which can be avoided with better standards of care; 7) the elemental role of the microbiology laboratory in the prevention and control of infections; 8) the unprecedented crisis due to the emergence of specific multi-resistant pathogens; 9) the risks for healthcare workers, such as tuberculosis, hepatitis, HIV, SARS, and hemorrhagic fevers; and 10) the need for the consistent application of guidelines. The second part of this review focuses on new challenges for infection control, such as 1) the ever-growing number of immunocompromised patients and basic control measures to avoid opportunistic infections; 2) the concerns about the capacity of the public health systems to deal with terrorist acts; 3) the practice of high-risk procedures in facilities lacking trained personnel, efficient laboratories, and protective items; and 4) gene therapy and its potential infectious complications. Consideration is given to the asymmetric development of infection control globally.

Communicable Disease Control↗

PVP-iodine in hydrosomes and hydrogel--a novel concept in wound therapy leads to enhanced epithelialization and reduced loss of skin grafts.

BACKGROUND: Moist wound treatment improves healing at a possibly increased risk of bacterial infection and many local antiseptics impair healing. A moist treatment modality with efficient antimicrobial activity would be desirable. METHODS: In this monocentric, randomized, observer blinded, phase III study, a new hydrosome polyvinyl-pyrrolidone (PVP)-iodine preparation in hydrogel containing iodine in a 3% concentration (Repithel) was investigated for its effect on epithelialization in patients receiving meshed skin grafts. Grafts of 167 patients (donor site defects, burn wounds, or chronic defects) were dressed either with Repithel (n=83) covered with a gauze (Jelonet), or Jelonet-gauze only (n=84) until healing. RESULTS: Grafts receiving Repithel healed significantly earlier (9.4 days versus 12.4 days; p<0.0001) and faster than controls as measured by neo-epithelialization of mesh holes between days 7 and 11 (91.2+/-22.8% versus 82.3%+/-28.6, p<0.0001). A subgroup analysis showed that the effects on grafted burn wounds (p=0.0042) and chronic defects (p<0.0001) was more significant than on donor sites. Also a higher take rate of grafts (p=0.0053) and a reduced loss of grafts was observed with Repithel treatment (8 grafts versus 20 grafts) (p=0.0063, respectively). Smokers had improved graft take (p=0.0069) and higher rate of epithelialization (p=0.0040) compared to smokers of the control group. CONCLUSIONS: The results demonstrate significant clinical advantages of Repithel. This new local wound healing drug combines antisepsis and wound moisture efficiently resulting in significantly enhanced epithelialization, decreased transplant losses, and significantly improved healing especially in smokers.

Anti-Infective Agents, Local↗

Does surgery unfavourably perturb the "natural history" of early breast cancer by accelerating the appearance of distant metastases?

This historical perspective on breast cancer tells us how and why certain therapeutic eras have reached ascendancy and then declined. Therapeutic revolutions occur after a crisis develops when there is a general recognition that clinical interventions are not producing positive results predicted by the prevailing paradigm. The attitude of pre-modern surgeons was influenced by the very real possibility of doing more harm than good by operating upon women with breast cancer. Up until Halsted, the general consensus was clearly that, unless forced by the circumstances, surgical resection should be avoided for disease much more advanced than very early stage tumours (the cacoethesis of Celsus). Twentieth century progress in antisepsis, anaesthesia, and surgery changed this point of view. The first three quarters of that century saw more and more aggressive operations performed while the last quarter century reversed this trend, with reduction of the size of breast cancer operations based largely on the teachings of Fisher. A new crisis is upon us now in that trials of early detection have resulted in unexpected disadvantages to certain subgroups and there is previously unreported structure in early hazard of relapse, clinical data that suggests the act of surgery might accelerate the appearance of distant metastases. The explanation we propose that agrees with these results, as well as physicians of antiquity, is that surgery can induce angiogenesis and proliferation of distant dormant micrometastases, especially in young patients with positive nodes.

Breast Neoplasms↗

A remarkable case in the history of obstetrical surgery: a laparotomy performed by the Dutch surgeon Abraham Cyprianus in 1694.

In 1700 the Dutch surgeon/medical doctor Abraham Cyprianus (1655/1660-1718) published his Epistola historiam exhibens foetus humani post XXI. menses ex uteri tuba, matre salva ac superstite excisi, a 94-page book in which several remarkable case histories are described and illustrated. The most spectacular case in the book is the accurate and detailed description of the delivery of a dead full-term child (ectopic tubar pregnancy) by a laparotomy he performed in a living woman in December 1694. The woman survived the operation and gave birth to three more children in following years. This remarkable, well-considered, brave and life-saving operation, performed in a time without antisepsis and anesthesia in a domestic situation is seldom mentioned by medical historians describing the history of obstetrics. This particular case is reviewed in this article.

Female↗

Evaluation of a 2% chlorhexidine gluconate in 70% isopropyl alcohol skin disinfectant.

The efficacy of a new skin disinfectant, 2% (w/v) chlorhexidine gluconate (CHG) in 70% (v/v) isopropyl alcohol (IPA) (ChloraPrep), was compared with five commonly used skin disinfectants against Staphylococcus epidermidis RP62A in the presence or absence of protein, utilizing quantitative time-kill suspension and carrier tests. All six disinfectants [70% (v/v) IPA, 0.5% (w/v) aqueous CHG, 2% (w/v) aqueous CHG, 0.5% (w/v) CHG in 70% (v/v) IPA and 10% (w/v) aqueous povidone iodine (PI)] achieved a log(10) reduction factor of 5, in colony-forming units/mL, in a suspension test (exposure time 30s) in the presence and absence of 10% human serum. Subsequent challenges of S. epidermidis RP62A in a biofilm (with and without human serum) demonstrated reduced bactericidal activity. Overall, the most effective skin disinfectants tested against S. epidermidis RP62A were 2% (w/v) CHG in 70% IPA and 10% (w/v) PI. These results suggest that enhanced skin antisepsis may be achieved with 2% (w/v) CHG in 70% (v/v) IPA compared with the three commonly used CHG preparations [0.5% (w/v) aqueous CHG, 2% (w/v) aqueous CHG and 0.5% (w/v) CHG in 70% (v/v) IPA].

2-Propanol↗

Putting the pieces together: Roger I. Lee and modern transfusion medicine.

Roger Irving Lee (1881-1964) played significant scientific and leadership roles in overcoming the clinical impediments to blood transfusion in the 1910s. He developed the first successful anticoagulant system, paraffinized glass, and the first sterile system for indirect transfusion without defibrination, the Lee-Vincent flask. He used citrate as an anticoagulant before those generally credited with its discovery did. He introduced surgical antisepsis of the donor site and a practical system for maintaining typed blood for a large hospital donor and transfusion service. He was Oswald Robertson's mentor at Harvard as well as his commanding officer in the Harvard Medical Unit on the Western Front during World War I. Lee sent Robertson to perform "his preserved blood cells transfusion" in the casualty clearing stations of the British Third Army and provided Robertson's group with O donors, enabling the most important medical development of the war. Lee put the pieces of modern blood banking and transfusion together.

Anticoagulants↗

From handmaiden to right hand--World War I--the mud and the blood.

By the beginning of World War I, modern innovations and advances in the field of medicine were common. Physicians knew about bacteria, how disease spread, and the importance of antisepsis. To prepare for the war, Great Britain developed elite corps of army nurses, fully-equipped military hospitals, and trained personnel who established field hospitals and base hospitals. Alice Fitzgerald, a nurse from Baltimore, was drawn into the conflict when she was asked to serve as the Edith Cavell Memorial Nurse with the British Army.

France↗

A randomized trial of povidone-iodine compared with iodine tincture for venipuncture site disinfection: effects on rates of blood culture contamination.

BACKGROUND: Contamination of blood cultures creates problems in their interpretation and unneeded resource utilization. Because skin flora comprise the major group of contaminant species, more effective skin disinfection at the venipuncture site could reduce contamination. SUBJECTS AND METHODS: We performed a randomized trial in adult inpatients at a tertiary care teaching hospital. Antecubital venipuncture sites were randomly disinfected with povidone-iodine or iodine tincture, and blood cultures (two bottles, 10 mL of blood) were drawn by professional phlebotomists. Scoring of contaminant species was restricted to skin flora. Hospital resource utilization was compared among patients with contaminated blood cultures and those with sterile blood cultures. RESULTS: Of the 3,851 blood cultures collected during the study, 120 (3.1%) were contaminated with skin flora. The contamination rate for blood cultures collected after povidone-iodine was 3.8% (74 of 1,947), compared with a rate of 2.4% (46 of 1,904, P = 0.01) after iodine tincture. The difference in mean total hospital costs for patients with contaminated blood cultures and those with sterile blood cultures was $4,100 (95% confidence interval: $740 to $7,400, P = 0.02). CONCLUSIONS: Iodine tincture is superior to povidone-iodine for venipuncture site antisepsis before blood culture sampling. Because of the high costs associated with contaminated blood cultures, hospitals should consider switching from povidone-iodine to iodine tincture. Reduction of the contamination rate may improve the quality of patient care and reduce hospital costs.

Adult↗

Reduction of infection after cardiac surgery: a clinical trial.

Between January 1, 1975, and June 1, 1984, 3,275 patients underwent cardiac operations with cardiopulmonary bypass. No operations were performed in 1978. In Phase I of the study, general operating rooms were used for cardiac operations, and standard methods of antisepsis and asepsis were used. Phase II began in January, 1979, with the opening of two specially constructed operating rooms with complete separation of incoming and outgoing personnel and supplies, and with a laminar airflow system. All personnel scrubbed 3 minutes and changed into autoclaved clothing before entering the operating suite, and scrubbed again for 5 minutes before putting on gowns. By Phase III, which began in July, 1982, all additional protocols against infection were in place including strict techniques in the intensive care unit and a continuous antiinfection surveillance program. In Phase I, 7.3% (70% confidence limits [CL] 6.4 to 8.2%) of patients had an infectious complication; in Phase II, 2.7% (CL 2.3 to 3.2%), and in Phase III, 0.8% (CL 0.5 to 1.2%). The reductions were similar in the four subtypes of infection (superficial presternal infection, mediastinitis, endocarditis, and septicemia). The study indicates that improving the surgical environment, improving the surgical and operating room protocols, and increasing the awareness of the dangers of infection among the personnel can strikingly reduce the incidence of infections after cardiac operations.

Bacterial Infections↗

[Current situation of colorectal trauma].

Mortality from colorectal trauma decreased from the end of the 19th Century, when death was the rule, to the 21st Century, when mortality is 5%. The greatest advances were produced during wars, mainly due to improved transport conditions, antisepsis, advances in operating and anesthetic techniques, the management of fluids, blood and blood products, the use of antibiotics, exteriorization of wounds, and the use of colostomy. Injuries to the anus, rectum and colon are infrequent. Their prevalence is difficult to establish because they can be caused by several factors. In Spain, the most frequent causes are traffic accidents and iatrogenic lesions, while in America the most common causes are stab or gunshot wounds. Although the etiology of these injuries is diverse, two major groups of colorectal trauma can be established: accidental injuries and iatrogenic trauma. Clinical symptoms vary, ranging from abdominal, pelvic, perianal or anal pain, sometimes associated with rectorrhagia, to peritonismus or shock. Diagnosis is based on physical and rectal examination and laboratory, radiological, and endoscopic investigations. Laparoscopy can also be used on occasions. Treatment should be individualized, depending on the patient's history, current status, the time elapsed since injury, the status of the injured intestine, the degree of fecal contamination, associated lesions, and the surgeon's experience.

Colon↗

Limited efficacy of alcohol-based hand gels.

Alcohol-based gels have been introduced recently in many hospitals worldwide for hand antisepsis. We investigated the antimicrobial efficacy of ten gels and four rinses according to European standards (EN 1500). No gel met the EN 1500 requirements within 30 s of application, whereas all hand rinses did. The tested hand gels should be considered a retrograde step for hand hygiene because the application time in clinical practice is often shorter than 30 s; they should not replace alcohol-based liquid hand disinfectants currently used in hospitals or be implemented as first choice agents.

1-Propanol↗

Drug intervention trials in sepsis: divergent results.

CONTEXT: Important advances have been made in our understanding of severe sepsis. Outcome can be improved by targeted interventions, including early and appropriate antibiotic therapy and goal-directed resuscitation, and might be further improved by selective decontamination of the digestive tract, tight control of glucose, and possibly by giving corticosteroids to selected patients. Drugs that target specific steps in the septic cascade include cytokine inhibitors, anti-endotoxins, and the three naturally occurring anticoagulants. Only one of these trials, which assessed the efficacy of activated protein C, reported significant improvements in outcome. Translation of these results into practice has been hampered by high drug costs, and by apparent discrepancies between interim results and final outcomes in two of the trials with natural anticoagulants. STARTING POINT: Recently, Steven Opal and colleagues (Crit Care Med 2004; 32: 332-41) reported a randomised trial with platelet-activating-factor acetylhydrolase to suppress the inflammatory response in septic patients. No effects on outcome were observed (mortality 24% with placebo vs 25% with the intervention). By contrast, Jose Garnacho-Montero and colleagues, in a cohort study (Crit Care Med 2003; 31: 2742-51), saw large mortality reductions with initially appropriate choice of antibiotics in septic patients (19.8% reduction overall and 43.4% in patients with septic shock). These benefits were higher than those even in the most successful trial with an antisepsis agents, underscoring the importance of basic measures in severe sepsis. WHERE NEXT? Initial management in severe sepsis should include early goal-directed fluid resuscitation, appropriate antibiotic treatment, and surgical-site control. Intensive-care units should be run by specialists, with adequate medical and nursing staffing. Tight regulation of glucose, selective decontamination of the digestive tract, and moderate-dose corticosteroids in selected cases should be considered. Expensive new drugs, such as activated protein C, might further improve outcome, but should be considered only when organisational aspects and supportive care have been optimised.

Antithrombin III↗

Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in southern Nepal: a community-based, cluster-randomised trial.

BACKGROUND: Omphalitis contributes to neonatal morbidity and mortality in developing countries. Umbilical cord cleansing with antiseptics might reduce infection and mortality risk, but has not been rigorously investigated. METHODS: In our community-based, cluster-randomised trial, 413 communities in Sarlahi, Nepal, were randomly assigned to one of three cord-care regimens. 4934 infants were assigned to 4.0% chlorhexidine, 5107 to cleansing with soap and water, and 5082 to dry cord care. In intervention clusters, the newborn cord was cleansed in the home on days 1-4, 6, 8, and 10. In all clusters, the cord was examined for signs of infection (pus, redness, or swelling) on these visits and in follow-up visits on days 12, 14, 21, and 28. Incidence of omphalitis was defined under three sign-based algorithms, with increasing severity. Infant vital status was recorded for 28 completed days. The primary outcomes were incidence of neonatal omphalitis and neonatal mortality. Analysis was by intention-to-treat. This trial is registered with , number NCT00109616. FINDINGS: Frequency of omphalitis by all three definitions was reduced significantly in the chlorhexidine group. Severe omphalitis in chlorhexidine clusters was reduced by 75% (incidence rate ratio 0.25, 95% CI 0.12-0.53; 13 infections/4839 neonatal periods) compared with dry cord-care clusters (52/4930). Neonatal mortality was 24% lower in the chlorhexidine group (relative risk 0.76 [95% CI 0.55-1.04]) than in the dry cord care group. In infants enrolled within the first 24 h, mortality was significantly reduced by 34% in the chlorhexidine group (0.66 [0.46-0.95]). Soap and water did not reduce infection or mortality risk. INTERPRETATION: Recommendations for dry cord care should be reconsidered on the basis of these findings that early antisepsis with chlorhexidine of the umbilical cord reduces local cord infections and overall neonatal mortality.

Administration, Topical↗