PAHO MoH Manual INFECTION PREVENTION AND CONTROL POLICIES PDF

TABLE OF CONTENTS Acknowledgements i Preface ii 1 Epidemiology of infectious diseases 1 1.1 Basic concepts on infection prevention and control 1 1.1.1 Definitions 1 1.2 Modes of transmission 4 1.2.1...

TABLE OF CONTENTS Acknowledgements i Preface ii 1 Epidemiology of infectious diseases 1 1.1 Basic concepts on infection prevention and control 1 1.1.1 Definitions 1 1.2 Modes of transmission 4 1.2.1 Contact transmission 4 1.2.2 Droplet transmission 4 1.2.3 Airborne Transmission 5 1.2.4 Food and Waterborne Transmission 5 1.2.5 Vector-borne Transmission 6 2 Standard Precautions 8 2.1 Hand hygiene 8 2.1.1 Skin physiology and microbiota 8 2.2 Hand hygiene practices 10 2.2.1 Hand washing 10 2.2.2 Alcohol-based solutions (alcohol-based hand rub – ABHR) 10 2.3 Respiratory hygiene and cough etiquette 12 2.4 Personal protective equipment 12 2.4.1 Gloves 13 2.4.2 Gown and apron 14 2.4.3 Facial mucous membrane protectors (mouth, nose, conjunctiva) 14 2.4.4 Eye protection 16 2.4.5 Donning and doffing PPE 17 2.5 Needlestick and other sharps-related injuries 20 3 Transmission-based precautions 22 3.1 Transmission-based precautions 22 3.1.1 Contact precautions 23 3.2 Droplet transmission 26 3.2.1 Patient placement 26 3.2.2 Room requirements 26 3.2.3 PPE to use and procedures to follow 27 3.3 Airborne transmission 29 3.3.1 Patient placement 29 3.4 Establishing priorities for single rooms 31 3.4.1 Cohort isolation 31 General cohort measures 31 3.4.2 PPE to use and procedures to follow 32 3.5 Elements necessary for defining the termination of additional precautions 32 4 Special considerations 33 4.1 Precautions to prevent multi-drug resistant agent infections of importance to public health 33 4.2 Special recommendations for paediatrics 36 4.2.1 Transmission by contact (Contact Precautions) 36 4.2.2 Droplet transmission 38 4.2.3 Airborne transmission 38 4.3 Infection prevention and control in hemodialysis 39 4.3.1 Hand Hygiene 38 4.3.2 Personal Protective Equipment 40 4.3.3 Cleaning and disinfection of environmental surfaces 40 4.3.4 Disinfection of the internal fluid pathway of hemodialysis machines 41 4.3.5 Handling of disposable supplies and reusable items in HD units 41 4.3.6 Water treatment: Purity and testing 41 4.3.7 Screening/routine serologic testing and patient placement 42 4.4 Infection prevention in post-mortem care 43 4.5 Tuberculosis 44 References 46 Appendix 1 – Carbapenem resistant organism (CRO) – Infection Prevention and Control 49 Appendix 2 – Checklist of PPE and cleaning equipment for isolation areas 51 Appendix 3 – Air changes per hour in natural ventilation conditions 52 LIST OF TABLES 35 Table 1 – The principal mechanisms or modes of transmission of infectious diseases 2 Table 2 – Possible interventions to break the chain of infection 3 Table 3 – Characteristics of the two main hand hygiene methods used as a standard precaution 9 Table 4 – Personal Protective Equipment 13 Table 5 – PPE use according to procedure involved (Examples) and Risk Assessment for exposure potential 16 Table 6 – Risk of infections after percutaneous exposures 20 Table 7 – Measures of containment of HAIs in endemic conditions for multi-resistant microorganisms 34 Table 8 – Measures of containment of HAI against outbreaks of multi-drug resistant microorganisms 35 Table 9 – Principal clinical conditions and aetiologies that require additional droplets precautions 37 Table 10 – Principal clinical conditions and aetiologies that require additional precautions by droplets 39 Table 11 – Recommendations on hepatitis B virus, hepatitis C virus and Human Immunodeficiency Virus (HIV) screening/testing and patient placement: 42 LIST OF FIGURES Figure 1 – Chain of transmission of infectious diseases 1 Figure 2 – Five moments of hand hygiene 9 Figure 3 – Hand washing technique 11 Figure 4 – Handrub technique 11 Figure 5 – Seal check for respirators 15 Figure 6 – Sequence of Donning PPE 18 Figure 7 – Sequence of Doffing PPE 19 Figure 8 – Contact isolation 25 Figure 9 – Droplet precaution 28 Figure 10 – Airborne precaution 30 Acknowledgements The Ministry of Health Trinidad and Tobago wishes to acknowledge all the staff responsible for update of this manual. While it is impossible to name everyone, who participated in the meetings and workgroups during the review and update of the Manual, we wish to acknowledge the contributions of: The Oversight Committee Members from the Pan American Health Organization/World Health Organization [PAHO/WHO] and the Ministry of Health. The multidisciplinary team of health professionals for their valuable comments/suggestions. PAHO/WHO for sponsoring the consultancy. We would like to thank the Focal point – Dr. Rajeev P. Nagassar, Specialist Medical Officer Microbiology, Head of Department Microbiology and Member of the National Coordinating Committee to Combat Antimicrobial Resistance, for leading this initiative. This manual was produced by the Principal Medical Officer - Institutions (Under the Office of the Chief Medical Officer), Ministry of Health of Trinidad and Tobago, in collaboration with The PAHO/WHO of Trinidad and Tobago. Copyright © 2021, Ministry of Health, Government of the Republic of Trinidad and Tobago. All rights reserved. No part of this publication may be reproduced, distributed or transmitted in any form or by any means without the prior written permission of the Government of the Republic of Trinidad and Tobago. i Preface The Government of the Republic of Trinidad and Tobago through the Ministry of Health has implemented a comprehensive Health Sector Reform Programme. This Programme is aimed at improving the quality of health care by introducing new organizational structures and systems, re-engineering ineffective systems and shifting expenditure to health promotion and disease prevention initiatives. In keeping with one of the main goals, which is to improve and maintain the quality of health care delivered to the population, the ministry has introduced a sector-wide comprehensive Continuous Quality Improvement [CQI] Programme. Key elements of the CQI Programme include Accreditation and Licensing; Monitoring and Audit; Training and Capacity Building; Risk Management; Quality Management Information Systems [QMIS]; Systems Re-engineering and Evaluation. In the context of the accreditation and risk management systems of the Quality Programme, the Ministry of Health has introduced a structured programme for the prevention and control of infection since it maximizes patient outcomes and is part of the Ministry’s strategy for providing safe, effective and efficient quality health services. In Trinidad and Tobago, like many other countries in the world, increasing numbers of different organisms are developing resistance to greater numbers of available antibiotics. Increased global travel is bringing more persons into contact with diseases, which are incubating; additionally, there are greater numbers of persons in a state of immune suppression who are more susceptible to invasion by pathogens [organisms causing diseases] or those usually considered non- pathogenic. It is also well recognized that poor infection prevention and control practices result in patient dissatisfaction, increases patient stay and overall costs including litigation. It is therefore imperative that a holistic approach be instituted to the prevention and control of infection in Trinidad and Tobago. To achieve this goal public and private sector partnership has become absolutely essential. It is also mandatory that all health care facilities implement the infection prevention and control policies and guidelines in order to reduce the risks and improve quality. The scope of the 3rd Edition of the Infection Prevention and Control Policies and Guidelines for Healthcare Services has been updated in four guidelines: Guideline 1 – Prevention and Control of Healthcare-associated infections Guideline 2 – Occupational safety and health Guideline 3 – Sterilization and Disinfection Guideline 4 – Environmental cleaning Guideline 5 – Healthcare-associated infections surveillance – To be released at a later date As Minister of Health, I give the assurance that patient safety is of utmost importance and that the necessary infrastructure and resources will be made available and I feel confident that you the health care professionals, managers, and support staff will ensure that the goals of the programme are achieved and maintained. We thank the Pan American Health Organization (PAHO) for partnering with us to achieve this revision of our manual. Chief Medical Officer Minister of Health ii 1. EPIDEMIOLOGY OF INFECTIOUS DISEASES 1.1 BASIC CONCEPTS ON INFECTION PREVENTION AND CONTROL The sequence of specific interactions, known as the chain of transmission (Figure 1) make it possible for an infectious agent to enter and affect a susceptible host. Figure 1 – Chain of transmission of infectious diseases Pathogen Susceptible Reservoir Host Portal Portal of Entry of Exit Mode of Transmission 1.1.1 DEFINITIONS Microorganism: Biological agent capable of coloniz¬ing or creating an infection in a host. Infection: Presence of a microorganism in the host tissue, where it lives, grows, multiplies, and induces an immune response in the host that generates signs and symptoms. Colonization: Presence of a microorganism in the host tissue, where it lives, grows, and multiplies but does not show signs or symptoms of active infection. It may or may not induce an immune response. Microorganisms may be bacteria, viruses, fungi, parasites, or prions. An agent that produces an infection has the following characteristics: Infective dose. Virulence: capacity of the agent to cause severe disease or death. Invasiveness: capacity of the agent to penetrate host tissues and multiply. Pathogenicity: capacity of the agent to cause disease through a variety of mechanisms. 1  Reservoir: Habitat in which microorganisms live, grow, and multiply. A reservoir may be an inanimate object, the environment, or an animate being, either animal or human. The main reservoir of agents responsible for HAIs is a patient infected or colonized by a microorganism, regardless of whether the agent is sensitive or resistant to antimicrobial drugs. Often the host is a healthy carrier of the microorganism who does not present symptoms of infectious disease, which makes it more difficult to identify the reservoir. Portal of exit: Point where the microorganism leaves the host, which tends to be the site where the agent is usually located. The main portals of exit are the upper respiratory tract, the lower digestive tract, and areas near breaks in the skin that are colonized or infected. Mechanism or mode of transmission: Manner or component by means of which the microorganism travels from the reservoir’s portal of exit to the portal of entry on the susceptible host (see examples of infections based on the mechanism of transmission in Chapter IV, Additional precautions based on mode of transmission). In the case of HAIs, the main mecha¬nisms of transmission are as follows (Table 1): Table 1 – The principal mechanisms or modes of transmission of infectious diseases Mechanisms or modes of transmission of hospital-acquired infections (HAI) Direct contact The microorganism goes directly from the reservoir to the susceptible host. This situation occurs in the direct transfer of blood or bodily fluids from a patient to another susceptible patient or to mucous membranes or injured skin of health workers Indirect contact The susceptible host comes into contact with the infective microorganism through an inanimate object (e.g., clothes, fomites, surfaces of the room) Droplet transmission Occurs when microorganisms are produced through the expulsion of particles (droplets) of 5 µ m to 100 µ m (micrometers) from the nose or mouth of an infectious patient (e.g., by coughing or sneezing). Microorganisms can travel 1 to 2 meters. They can also be transferred indirectly by touching contaminated surfaces Airborne transmission Occurs by dissemination of airborne droplet nuclei /small particles (< 5 µ m) containing infectious agents that remain infective over time and distance (e.g., spores of Aspergillus spp., and Mycobacterium tuberculosis). Microorganisms carried in this manner may be dispersed over long distances by air currents and may be inhaled by susceptible individuals who have not had face-to-face contact with or have been in the same room with the infectious individual Table 2 presents the possible interventions to break the chain of infection. 2  Table 2 – Possible interventions to break the chain of infection Component of the chain Conditions Possible interventions Infection Specific antibiotic treatment shortens the infectious Reservoir period Environmental and fomites contamination Cleaning, disinfection, and sterilization to disrupt the Portal of exit chain of transmission Alive Transmission mechanism (patients, health workers) Immunization or Eradication/decolonization therapy in healthy carriers Environment and fomites Portal of entry Cleaning, disinfection, and sterilization to disrupt the Equipment, devices and others chain of transmission Susceptible host Droplets Antisepsis, sterilization Contact Aseptic technique, Standard precautions, Additional precautions Airborne Standard precautions Prevention Additional precautions Protection Aseptic technique Standard precautions Additional precautions, according to mode of transmission Immunization Specific prophylaxis Proper therapeutic management of disease In these Guidelines each of these measures will be reviewed in detail from a practical approach to be accomplished in any pa- tient’s health care regardless of its setting. 3  1.2 MODES OF TRANSMISSION 1.2.1 CONTACT TRANSMISSION This is the most frequent mode of transmission of nosocomial infection 1. Direct contact: when the infective microorganisms travel from the reservoir to the susceptible person. Examples: (1) direct contact between the blood or body fluids containing the infective microorganism in a patient with Ebola virus disease and the mucous membranes or skin lesions of a caregiver or nearby patient who was not using protective barriers or performing hand hygiene; (2) direct contact without gloves between a health worker or another patient and a nearby patient who has scabies; (3) direct hand contact, without gloves, between a health worker and a patient with oral herpes simplex 1 lesions, leading to subsequent appearance of a herpes whitlow on the finger that was in contact with the patient’s mouth 2. Indirect contact: the susceptible person (host) acquires the infective microorganism through an intermediary (e.g., environment (inanimate), healthcare workers or another patient (animated). The infective agent should have the capacity to survive in the environment, however the detection of this in the environment does not necessarily explain the transmission of the infection. An analysis should be completed to determine if the organism is contributing to the infection. Examples: (1) transmission of Clostridium difficile spores on the hands of a health worker from a symptomatic in-fected patient to a susceptible host (for example, by handling feces without using gloves), (2) transmission of respiratory syncytial virus (RSV) particulates on a toy that was in contact with a symptomatic patient and passed on to a susceptible host who touched the toy and then touched his or her facial mucous membranes, and (3) transmission of hepatitis C virus from an infected dialysis patient to other susceptible dialysis patients by administering a drug from a multidose syringe shared by health workers with more than one patient. Microorganisms transmitted through contact transmission: Acinetobacter spp, Clostridium difficile, `Enterococcus` spp (including vancomycin-resistant strains, VRE), Pseudomonas aeruginosa, Klebsiella spp, Staphylococcus aureus (includes methicillin-resistant strains, MRSA), norovirus, `respiratory syncytial virus`, rotavirus, Gram-negative bacilli including Enterobacteriaceae resistant to the antimicrobial drugs (for example: producers of Extended Spectrum Betalactamase (ESBL) or carbapenemases ). 1.2.2 DROPLET TRANSMISSION Respiratory drops (droplets) that range between 5 and 100 μm in diameter are released from the respiratory tract upon coughing, speaking or sneezing and measure 20 μm in diameter, which means that they can remain in suspension for only a few seconds (smaller droplets can stay in suspension for up to a few minutes). These droplets carry microorganisms (infecting or colonizing patient’s oral cavity) that can be transferred to a recipient person and contaminate surroundings They do not have the capacity to travel farther than 1 meter from the person who emits them. Droplet transmission, as with contact transmission, can be indirect (through an intermediary) or direct (without one). 1. Droplets: These are created when an infective patient transmits microorganisms within particles (droplets) ranging from 5 μm (microns) to 100 μm in diameter. They usually come from the respiratory tract (mouth or nose) in the course of coughing, sneezing, or speaking and measure 20 μm in diameter, which means that they can remain in suspension for only a few seconds (smaller droplets can stay in suspension for up to a few minutes). They do not have the capacity to travel farther than 1 meter from the person who emits them. Droplet transmission, as with contact transmission, can be indirect (through an intermediary) or direct (without one). 4 2. Droplet nuclei (airborne transmission): Alternatively, when microorganisms are transmitted via particles smaller than 5 μm in diameter, they can stay airborne for prolonged periods and are capable of traveling longer distances than droplets when moved by air currents. Once they are airborne, they can be inhaled and enter the alveoli of individuals sharing the same room, even if these individuals have not had direct contact with the infected patient. Droplet nuclei can be generated directly by patients through a cough or sneeze (as in the case of tuberculosis) or during procedures such as tracheal intubation, noninvasive positive-pressure, BASIC RECOMMENDATIONS 25, ventilation, invasive high-frequency ventilation, pre- and post-intubation airway aspiration, tracheotomy, respiratory kinesiotherapy, nebulization, fibro bronchoscopy, resuscitation, sputum induction, or centrifugation of samples and instruments used to cut tissues Microorganisms that are transmitted through droplet transmission; Diphtheria, whooping cough (B. pertussis), meningitis by N. menin- gitidis, influenza, rhinovirus, adenovirus. 1.2.3 AIRBORNE TRANSMISSION Airborne particles can be transmitted when an infected patient coughs or sneezes and also when performing clinical procedures that include: tracheal intubation, tracheotomy, non-invasive respiratory ventilation with positive pressure, invasive mechanical ventilation of high frequency, aspiration of airway, respiratory therapy, bronchoscopy, induction of sputum, centrifugation of samples, resuscitation and procedures with air drills. The greater risk procedures are tracheal intubation, non-invasive mechanical ventilation, tracheotomy, and manual ventilation. Microorganisms transmitted through airborne transmission: Mycobacterium tuberculosis (patients with TB bacilli); virus measles, vari- cella zoster (Chicken pox), herpes disseminated zoster, amongst other pathogens. 1.2.4 FOOD AND WATERBORNE TRANSMISSION Food and water borne transmission applies to micro-organisms transmitted by contaminated items such as: Foods – e.g., salmonellosis Water – e.g., shigellosis These serve to transmit infection to multiple hosts. Such transmission may result in an explosive outbreak. Environmental sources of con- tamination also may contain a mixture of human and animal pathogens, emphasizing the potential for introduction of animal pathogens into the food chain through routes that are not controlled. Thus, a One Health approach must always be considered. Demand for seasonal produce all year has globalized the food market, with the challenge to work with the same highest hygienic standards across the world. These food production programmes illustrate the vulnerability of the global food supply: contamination may occur with pathogens from across the globe if there is a flaw in the process, including those that have recently emerged such as SARS-CoV-2. Careful review of pos- sible scenarios that may require our attention for the future of food safety is of utmost importance. The main steps to for safe food handling include: Clean — Wash hands and surfaces often Separate — Don’t cross-contaminate Keep worktops clean Separate raw food, such as meats, from ready to cook food, such as vegetables Check labels for expiry dates, for example Cook — Cook to the right temperature Chill — Refrigerate promptly 5 In hospital kitchens persons may use diluted bleach or vinegar to wash vegetables and other products. Vinegar is preferable. Water-related diseases can be classified into 4 major categories, as follows: 1: Water-borne diseases: infections spread through contaminated drinking water 2: Water-washed diseases: diseases due to the lack of proper sanitation and hygiene 3: Water-based diseases: infections transmitted through an aquatic invertebrate organism 4: Water-related vector-borne diseases: diseases transmitted by insects that depend on water for their propagation Water is a major reservoir for many organisms that cause diarrhea. Swimming pools have been associated with outbreaks of Shigella organisms, and Aeromonas species are associated with exposure to the marine environment. Water borne diseases may present with diarrhoea or may not. Waterborne bacteria that may be transmitted solely through oral route include the following pathogens –Bacteria: Campylobacter jejuni/coli, E. coli – enterohaemorrhagic, Legionella spp, Salmonella typhi, Shigella spp, Vibrio cholerae, Yersinia enterocolitica, Pseudomonas aeruginosa. The orally transmitted viruses include Adenoviruses, Enteroviruses (Polio), Hepatitis A, Hepatitis E, Noroviruses and Sapoviruses, Rotavirus. The protozoa include Cryptosporidium parvum, Entamoeba histolytica, Giardia lamblia/intestinalis, Naegleria fowleri and Toxoplasma gondii, while the Helminths include Dracunculus medinensis and Schistosoma spp. In as much as there are many sources of water it is an established fact that hospital water distribution systems might be the most overlooked, important and controllable source of healthcare-associated infections (HAIs). This is so because hospital water and water-related devices as well as moist environments and aqueous solutions can serve as a reservoir of waterborne pathogens in healthcare settings. 1.2.5 VECTOR-BORNE TRANSMISSION Vector-borne transmission refers to transmission by insect vectors and is prevented by appropriate health care facility construction and maintenance, closed or screened windows, and proper housekeeping. In addition, nets may be used over beds. Vector-borne transmission occurs when vectors such as mosquitoes, flies, rats and other vermin transmit micro-organisms. There are several vector-borne infections including viruses (Chikungunya, Dengue, Rift Valley fever, Yellow Fever, Zika, Japanese encephalitis, West Nile fever); parasites (Lymphatic filariasis, Malaria, Chagas disease - American trypanosomiasis. All the viruses mentioned above are transmitted by mosquito species (Aedes, Anopheles and culex) and according to the WHO, vector-borne diseases are one of the greatest contributors to human mortality and morbidity in tropical settings and beyond. Although significant progress is currently being made in combating some diseases such as malaria, lymphatic filariasis and Chagas disease, other diseases such as dengue continue to spread and increase their number of cases at an alarming pace. The silent expansion of mosquito vectors and their ability to develop resistance to insecticides threatens the gains made through vector control and calls for concerted planning and collaboration across sectors including health, agriculture, and the environment. In areas where vector-borne diseases overlap, integrated management of insecticide resistance is essential, supported by adequate capacity of trained personnel and resources. Environmental changes have also facilitated the recent spread of some diseases in rural areas. This has major implications for health systems, straining the limited resources in many developing countries. Events in the past five years – simultaneous outbreaks in several countries and the emergence of vector-borne diseases in new parts of the world – clearly highlight the increasing threat of these diseases to global public health. 6 Vector control programs need to adapt to match the changing epidemiological patterns of new emerging threats. This will require increased research to develop a sustained approach to ecological and environmental changes in the years ahead. Prevention and control of these viral diseases definitely will hinge on vector control. Control Methods include physical, biological and chemical methods. Please contact the Insect Vector Control Division (IVCD) for further information. 7 2. STANDARD PRECAUTIONS According to available scientific evidence, interventions that yield the best results are those that are allowed to be used only if they are performed correctly, which often require structural and cultural changes on the part of health teams. So far, no single method has been discovered that meets all of these requirements with respect to healthcare-associated infections (HAIs). However, there is consensus on some of the basic elements that will help ensure sustained appli¬cation of standard precautions, as well as other measures designed to reduce the incidence of HAIs. Standard precautions represent the minimum infection prevention practices that apply to all patient care, regardless if the patient is known to have an infection or not (e.g., assume everyone you come in contact with has an infectious agent in their blood and/or body fluid). Elements of Standard Precautions include the following: hand hygiene, use of personal protective equipment, respiratory hygiene and cough etiquette, safe handling of sharps materials, Appropriate decontamination of medical equipment Safe laundry practices Environmental cleanliness Safe waste management Standard Precautions Golden Rules Healthcare workers assume any patient they take care of may have an infectious disease Healthcare workers implement standard precautions whether patient shows symptoms or not Healthcare workers protect themselves and patients 2.1 HAND HYGIENE 2.1.1 SKIN PHYSIOLOGY AND MICROBIOTA Hands normally contain microorganisms (referred to as superficial bacterial flora), as well as, transitory flora acquired by contact with patients and contaminated environments. Contaminated hands of healthcare workers (HCWs) can then transfer germs to other patients and their environment or to themselves if they touch their eyes, nose or mouth. Hence, hand hygiene in HCWs is a fundamental issue to protect themselves and patients (Figure 2). Two methods have been defined for hand hygiene (Table 3): Hand washing with water and soap and drying with single-use towel Hand rubbing with alcohol-based solutions 8  Table 3 – Characteristics of the two main hand hygiene methods used as a standard precaution Hand washing Application of alcohol-based solution Scrubbing of the hands with soap and water and then rinsing, Scrubbing or rubbing of the hands with an alcohol-based usually under a stream of water, to remove microorganisms by solution to remove microorganisms through the microbicidal wiping them away and removing the chemical product. effect of the alcohol. Between 0.6 and 1.1 log10 CFUs are removed in 15 seconds and Between 3.2 and 5.8 log10 CFUs are removed in 10 seconds between 1.8 and 2.8 log10 CFUs are removed in 30 seconds. Note. CFUs = colony-forming units. Adapted from: Widmer AF. Replace hand washing with use of a waterless alcohol hand rub? Clin Infect Dis. 2000;31(1):136-43. Figure 2 – Five moments of hand hygiene Ndjg*bdbZcih[dg Ndjg bdbZcih[dg Design: mondofragilis network =6C9 =N:C: =6C9=N:C: DG:6H: 7:; I6H@ EI> 8 ' & 7:;DG: E6I>:CI 8DCI68I ) 6;I:G E6I>:CI 8DCI68I ( J >9 6;I  ;A :ME : G  7 D 9 N DHJ G : G > H @ * 6;I:G8DCI68I L>I=E6I>:CI HJGGDJC9>C10mm, clear chest X-ray; prophylactic treatment is offered for three (3) months. Rotate staff out of Medical Wards according to schedules as stipulated by national authorities. 45  References Aronson, M. D., and D. H. Bor.. Blood cultures. Ann. Intern. Med. 1987;106:246–253. Arpi M, Bentzon MW, Jensen J, Frederiksen W. Importance of blood volume cultured in the detection of bacteriemia. Fur. J. Clin. Microbiol. Infect. Dis. 1989; 8:838-842. Broaddus C, Dake MD, Stulburg MS, et al. 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