Autorisatiedatum: 29 augustus 2024

Eerstvolgende beoordeling actualiteit: 2026

Geautoriseerd door:

• Nederlandse Vereniging voor Medische Microbiologie
• Nederlandse Vereniging voor Dermatologie en Venereologie
• Nederlandse Vereniging voor Heelkunde
• Nederlandse Vereniging voor Oogheelkunde
• Nederlandse Orthopaedische Vereniging
• Nederlandse Vereniging voor Reumatologie
• Nederlandse Vereniging voor Thoraxchirurgie
• Nederlandse Vereniging voor Kindergeneeskunde
• Nederlandse Vereniging van Arbeidshygiëne
• Vereniging voor Hygiëne & Infectiepreventie in de Gezondheidszorg
• Patiëntenfederatie Nederland

Regiehouder:

• Samenwerkingsverband Richtlijnen Infectiepreventie

De ontwikkeling/herziening van deze richtlijnmodule is ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten en is gefinancierd door het ministerie van VWS Ministerie van Volksgezondheid, Welzijn en Sport (Ministerie van Volksgezondheid, Welzijn en Sport). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Wanneer de huidbarrière wordt doorbroken, kunnen bacteriën worden geïntroduceerd met het risico op het ontstaan van een infectie. Een van de maatregelen om het risico op een infectie te verminderen is het desinfecteren van de huid voorafgaand aan het moment dat deze barrière door medisch handelen wordt doorbroken.

In de praktijk bestaat er vanuit infectiepreventie-oogpunt discussie over het nut en de noodzaak van huiddesinfectie voorafgaand aan bloedafname ten behoeve van diagnostiek inclusief keuringen. Dit in tegenstelling tot wanneer er bloed wordt afgenomen ten behoeve van bloedkweken, bloedtransfusie of wanneer de huidbarrière wordt doorbroken bij het inbrengen van een intravasculaire katheter waarbij het nut en de noodzaak voor huiddesinfectie wel wordt gezien.

Ook bestaat er al langere tijd discussie over het feit of huiddesinfectie nodig is voorafgaand aan het toedienen van medicatie (waaronder ook vaccinatie, insuline) via een intramusculaire, subcutane of intradermale injectie.

Ook zijn er in de praktijk verschillende middelen die worden gebruikt voor desinfectie van de huid voorafgaand aan bloedafname of injectie. Gezien de praktijkvariatie, is het doel van deze module om te onderzoeken of een bepaald middel wetenschappelijk aantoonbaar de voorkeur heeft en op welke wijze het middel gebruikt dient te worden.

Concluderend is het doel van deze module om te beschrijven wat de plaats is van huiddesinfectie voorafgaand aan een bloedafname en een injectie (intramusculair, subcutaan, intradermaal) en welk huiddesinfectiemiddel hierin de voorkeur heeft op het voorkómen van een (lokale/systemische) infectie bij de patiënt en op het reduceren van het risico op contaminatie van het bloedmonster (in het geval van bloedafname).

Sub-question 1 Added value of skin disinfection prior to venous blood sampling

For this question, a systematic review of the literature was performed to answer the following question:
What is the added value of skin disinfection prior to venous blood sampling (exclusion: blood sampling for culture/identifying microbes, blood transfusion or insertion catheter)?

P: Patients eligible for venous blood sampling (exclusion: blood transfusion or insertion catheter)
I: Skin disinfection prior to venous blood sampling
C: No skin disinfection prior to venous blood sampling
O: Infection, blood culture contamination

Sub-question 2 Added value of skin disinfection prior to injection

For this question, a systematic review of the literature was performed to answer the following question:
What is the added value of skin disinfection prior to intramuscular, subcutaneous, or intradermal injection on the prevention of post-injection infection?

P : Patients receiving injection (intramuscular, subcutaneous, intradermal)
I : Skin disinfection prior to injection (intramuscular, subcutaneous, intradermal) of a medicinal substance
C : No skin disinfection prior to injection (intramuscular, subcutaneous, intradermal) of a medicinal substance (e.g., vaccination, insulin injection)
O: Local or systemic infection

Sub-question 3 Antiseptic skin preparation agents

For this question, a systematic review of the literature was performed to answer the following question:
Which skin antiseptic agent is the safest in use and most effective to prevent infection and contamination prior to blood sampling for diagnostic and screening purposes and prior to injections (intramuscular, subcutaneous, and intradermal)?

P: Skin disinfection before venous blood sampling and injection (intramuscular, subcutaneous, intradermal) of a medicinal substance
I: Antiseptic skin preparation agents, (alcohol, isopropyl, ethanol, povidone-iodine, chlorhexidine)
C: Antiseptic skin preparation agents, (alcohol, isopropyl, ethanol, povidone-iodine, chlorhexidine)
O: Infection, side effect, blood culture contamination regarding venous blood sampling

Relevant outcome measures

• For sub-question 1, the guideline development group considered infection and blood culture contamination as critical outcome measures for decision making.
• For sub-question 2, the guideline development group considered infection as a critical outcome measure for decision making.
• For sub-question 3, the guideline development group considered infection, side effects, and blood culture contamination as critical outcome measures for decision making.

A priori, the working group did not define the outcome measures listed above but used the definitions used in the studies. The working group defined a 25% relative difference for dichotomous outcomes (RR < 0.8 or > 1.25), and a 10% for continuous outcomes as a minimal clinically (patient) important difference.

Search and select (methods)

Sub-question 1: Added value of skin disinfection prior to venous blood sampling

The databases Embase (via embase.com), Medline (via OVID) and Cinahl were searched with relevant search terms until 20 December 2022. The detailed search strategy is available on request (via info@sri-richtlijnen.nl). The systematic literature search resulted in 132 hits. Studies were selected based on the following criteria:

• Systematic review (detailed search strategy, risk of bias assessment, and results of individual comparative studies available), randomised control trial, observational comparative study, and guideline;
• Research question includes all elements of the PICO;
• Full text available;
• Full text written in English or Dutch.

Based on title and abstract screening, thirteen studies were selected. After reading the full text, all studies were excluded (see Literatuursamenvatting Module 1.2 Bloedafname en injecties under the tab Onderbouwing). Important study characteristics and results are summarised in the Evidence table. The assessment of the risk of bias is summarised in the Risk of bias table.

Sub-question 2: Added value of skin disinfection prior to injection.

The databases Embase (via embase.com), Medline (via OVID) and Cinahl were searched with relevant search terms until 20 December 2022. The detailed search strategy is available on request (via info@sri-richtlijnen.nl). The systematic literature search resulted in 760 hits. Studies were selected based on the following criteria:

• Systematic review (detailed search strategy, risk of bias assessment, and results of individual comparative studies available), randomised control trial, observational comparative study, and guideline;
• Research question includes all elements of the PICO;
• Full text available;
• Full text written in English or Dutch.

In total, eighteen studies were initially selected based on title and abstract screening. After reading the full text, fifteen studies were excluded (see Table of excluded studies), and three studies were included. Important study characteristics and results are summarised in the evidence table. The assessment of the risk of bias is summarised in the Risk of bias table.

Sub-question 3: Antiseptic skin preparation agents.

The databases Medline (via OVID), Embase (via embase.com), and Cinahl were searched with relevant search terms until 22 December 2022. The detailed search strategy is available on request (via info@sri-richtlijnen.nl). The systematic literature search resulted in 954 hits. Studies were selected based on the following criteria:

• Systematic review (detailed search strategy, risk of bias assessment, and results of individual comparative studies available), randomised control trial or observational comparative study;
• Research question includes all elements of the PICO;
• Full text available;
• Full text written in English or Dutch.

First, systematic reviews (SRs) and randomised control trials (RCTs) were selected if they complied with the PICO. Based on title and abstract screening, 49 studies were selected. After reading the full text, 45 studies were excluded (see Table of excluded studies) and one SR and three RCTs were included. These four studies compared antiseptic agents prior to venous blood sampling and reported blood culture contamination as an outcome. The SR included eight studies, of which four did not meet our selection criteria. Therefore, a total of seven studies are included.

None of the SRs and RCTs reported infection or side effects as an outcome following venous blood sampling or intramuscular, subcutaneous, intradermal injection. Therefore, observational studies were selected if they compared antiseptic agents prior to venous blood sampling or injection (intramuscular, subcutaneous, or intradermal) and reported infection and/or side effects as outcomes. Based on title and abstract screening, twelve studies were selected. After reading the full text, all observational studies were excluded (see table of excluded studies). Important study characteristics and results are summarised in the evidence table. The assessment of the risk of bias is summarised in the Risk of bias table.

Description of studies

Sub-question 1 Skin disinfection venous blood sampling

It was not possible to provide a summary of literature because of the absence of relevant studies.

Sub-question 2 Skin disinfection injection

Intramuscular and subcutaneous injections

Wong (2019) conducted a randomized controlled trial determining the effectiveness of alcohol in reducing local skin reactions and infection post-vaccination. The study was carried out in a Canadian pediatric clinic between May and November 2017. Four hundred and two children were assessed for eligibility from which 170 children were included. Two hundred and thirty-two children were excluded because they did not meet inclusion criteria, refused to participate, or were not approached. The intervention group received an alcohol swab at the pre-defined injection site(s) prior to injection and the control group received an alcohol swab adjacent to the pre-defined injection site. All participants received between one and four vaccinations by a research assistant. Afterwards, parents assessed the injection sites and recorded local skin reactions (pain, redness, swelling, warmth, and spontaneous drainage of pus from the injection site) using a paper diary for two weeks (day 0-14). Parents were approached by telephone 24 hours (Day 1), 5 days (Day 5), and 14 days (Day 14) post-vaccination and questioned whether local skin reactions were present. Infection was considered for local skin reactions present on or after day 5 post-vaccination and parents were asked to visit the pediatrician with their child. In case cellulitis or an infectious abscess was suspected in accordance with the Brighton Collaboration criteria, parents were asked informed consent to take aspiration of the injection site to aid in the diagnosis.

Intramuscular, subcutaneous, and intradermal injections

Khawaja (2013) conducted a quasi-experimental study assessing the need for use of skin preparation using a 70% isopropyl alcohol swab prior to intramuscular, subcutaneous, or intradermal injection. Patients with skin disease and co-morbidity (e.g., immunosuppressed or heart valve disease) were excluded. The study was carried out in a hospital in Saudi-Arabia between August 2012 – December 2012. Patients were allocated to the intervention group (skin preparation with alcohol swab) or to the control group (no skin preparation) prior to abovementioned three types of injection. In the intervention group, the site of injection was disinfected with the 70% isopropyl alcohol swab for 30 seconds and allowed to dry for 30 seconds before injection took place. The injection site was assessed for erythema, pain, swelling, fever, and abscess formation on day 2-3. Patients positive for one or more of these signs or symptoms, were asked to monitor the injection site and report the redness, tenderness, or another abnormal signs. This group was followed over a period of three weeks on a weekly basis by a family physician (blind to swab status).

Subcutaneous injection

Koivisto (1978) conducted a cross-over study determining whether omission of skin preparation with 70% isopropyl alcohol prior to insulin injection resulted in infection at the injection site. The study was carried out by the department of internal medicine of the Yale University School of Medicine in the USA. During a 3 – 5-month period, insulin-dependent diabetic patients were asked to omit skin preparation before insulin injection in each alternate week. Patients were asked to monitor the injection site and record the following signs: redness, tenderness, or any another abnormal sign. The injection sites were inspected by the researchers every two weeks. In total, 13 patients were involved who administered more than 1700 injections without skin preparation.

Sub-question 3 Skin antiseptic agents venous blood sampling and injection

Infection

No studies were found.

Side effects

No studies were found.

Blood culture contamination

Martinez (2017) carried out a multicenter randomized controlled trial to evaluate the effectiveness of isopropyl alcohol (IPA) and chlorhexidine gluconate in isopropyl alcohol (CHG) on blood culture contamination rates. The study was conducted at two teaching hospitals in Mexico and included patients aged sixteen years or older suspected of having a bloodstream infection (BSI) who were admitted to the emergency room, internal medicine ward, or intensive care unit. A set of blood cultures were taken, which consisted of at least two cultures from different sites and at least one had to be from a peripheral vein. Blood culture samples were collected by trained nurses from a catheter care unit. First, all patients received skin preparation with isopropyl alcohol, with repeated back-and-forth strokes for 30 seconds (s). Then, either IPA or CHG was applied by an applicator. Blood culture samples were incubated for up to 5 days at 35^oC ± 1^oC in a BacT/Alert 3D system. The microbiologist determined if the blood culture sample was true positive, contaminated, or negative and performed identification and susceptibility tests for the isolated microorganisms. A blood culture sample was considered contaminated if one of two blood culture samples was exhibited the growth of one of the following microorganisms: coagulase-negative Staphylococcus, Corynebacterium spp., Bacillus spp., Propionibacterium spp., Micrococcus spp., or ⍺-hemolytic viridans group streptococci, or when the same organism was not isolated from ananother potentially infected site. A total of 1,102 sets of blood culture samples were obtained. Information on the concentration of isopropyl alcohol used prior to the application of the skin antiseptic agents that were compared to each another was not reported.

Story-Roller (2016) conducted a randomized cross-over trial to assess the effectiveness of CHG and iodine tincture (IT) on blood culture contamination rates. The study was conducted among patients suspected of having a BSI, and therefore, a set of blood cultures (one aerobic and one anaerobic) were taken per patients. Eight nursing units in an American hospital participated in the study from July 2014 and June 2015. Blood culture samples were drawn by trained nurses utilized aseptic technique. After a 3-month period, the units switched to the another antiseptic agent without a wash-out period. This alternating skin disinfection method was carried out on a quarterly basis for a one-year period. First, all patients received skin preparation with IPA for 30 s, followed by the application of either IT or CHG. The IT was administered in concentric circles moving away from the venepuncture site to an approximately 5-cm diameter, and allowed to dry for 30 s. The CHG was administered in a back-and forth motion over the venepuncture site to cover an area approximately 5-cm diameter, and allowed to dry for 30 s. The blood culture samples were incubated at 35^oC using Bactec FX system for five days. Positive cultures were further subcultured and processed using standard laboratory techniques. A blood culture sample was considered contaminated if only in one of two blood culture sample exhibited the grow of common skin organisms, including coagulase-negative Staphylococcus, viridans group streptococci, Bacillus spp., Neisseria spp. (another than Neisseria meningitidis or Neisseria gonorrhoeae), Micrococcus spp., or aerobic gram-positive rods. The investigator compared the blood culture samples considered as contaminated with the clinical presentations by reviewing the electronic medical record of these patients to confirmed that they were true false positive. A total of 6,095 blood culture sample sets were obtained. Information on the concentration of isopropyl alcohol used prior to the application of the skin antiseptic agents that were compared to each another was not reported.

Washer (2013) conducted a randomized crossover trial to evaluate the effectiveness of 10% povidone iodine aqueous solution (PI), IT, and CHG on blood culture contamination rates. The study was carried out among adult patients for whom clinicians had ordered blood culture samples at three medical-surgical units in an American University hospital from May 2008 through September 2009. All blood culture samples were obtained by trained phlebotomists. Prior to the application of PI or IT, the skin was first scrubbed with an alcohol prep pad for 30 s. Then either PI or IT was applied in concentric circles away from the venepuncture site, to cover an area 4 - 5 cm in diameter. PI was allowed to dry for 60 s, and IT was allowed to dry for 30 s before venepuncture. In case of iodine allergy, skin antisepsis with alcohol only was used. The CHG was applied directly onto the skin without prior disinfection with an alcohol prep pad. CHG was applied in a back-and-forth motion over the venepuncture site to cover an area 4 - 5 cm in diameter. Then CHG was allowed to dry for 30 s before venepuncture. After skin disinfection, the venepuncture site was not palpated (again). After a 5-month period, the units switched to the another antiseptic agent with a 1-month washout period. Aerobic and anaerobic bottles were incubated at 37^oC for 5 days (or longer if requested) using BacTAlert system. Positive cultures were further subcultured and processed using standard laboratory techniques. Two infectious diseases physicians examined the positive cultures and classified them as either true positive or contaminated. A blood culture sample was considered contaminated if only in one of two blood culture sample exhibited growth of common skin organisms, including aerobic gram-positive rods, Lactobacillus spp. Propionibacterium acnes (currently Cutibacterium acnes), Micrococcus spp., Bacillus spp. (not B. anthracis or B. cereus), coagulase-negative Staphylococcus, Neisseria spp. (another than Neisseria meningitidis or Neisseria gonorrhoeae), or 𝜸-hemolytic streptococci (not Enterococcus spp.). A total of 12,904 blood culture samples were collected from 3,879 patients. Hundred eighteen blood draws were audited regarding adherence on aseptic technique. Information on concentration of the isopropyl alcohol pad and drying time prior to the use of PI and IT was not reported.

Suwanpimolkul (2008) carried out a randomized controlled trial to evaluate the effectiveness of CHG and PI on blood culture contamination rates. The study was conducted among adult patients who were suspected of having bacteremia admitted to medical wards, intensive care units, and emergency room at a hospital in Thailand from August to October 2006. Blood culture samples were drawn by students, residents, or nurses. Both skin antiseptic agents were applying twice according to the institutional protocol and allowed to dry for approximately 1 min after the application. The septa of the culture bottles were wiped with a PI-pad before inoculation. The needle switch approach was not used. The 5-ml sample was inoculated into an aerobic bottle of blood culture broth, and then incubated at 37^OC for 7 days. Positive cultures were further subcultured and processed using standard laboratory techniques. A blood culture sample was considered contaminated if: (a) only in one of two blood culture sample exhibited growth of the following common skin organisms without isolation of the same organism from ananother potentially infected site: a common skin flora including coagulase-negative Staphylococcus, Corynebacterium spp., Micrococcus spp., Bacillus spp., or Propionibacterium spp., and (b) a common skin flora was isolated in a patient with incompatible clinical features, no attributable risks, and improvement without specific treatment for that organism. A total of 2146 blood culture samples were collected from 1,730 patients. The study did not report whether personnel who collected the blood samples were trained in technique.

Calfee (2002) conducted a randomized, crossover trial to evaluate the effectiveness of PI, IPA, IT, or povidone-iodine in 70% ethyl alcohol (Persist) on blood culture contamination. The study was carried out among patients admitted the emergency room (ER) and on all inpatient care units, excluding the neonatal intensive care unit, at an American hospital for 1 year in 1999 and 2000. Blood culture samples were drawn by trained physicians, nurses, and phlebotomists. The four skin antiseptic agents were packaged in envelopes. Each envelope contained three swabsticks soaked in the respective antiseptic agent. The venepuncture site was disinfected by using the three swabsticks one after ananother, beginning in the center and continuing in an outward direction using circular strokes for an area 5 – 7 cm in diameter successively and allowed to dry for at least one min. Culture bottles (aerobic and anaerobic) were inoculated by using the same needle used to perform venepuncture. After a 3-month period, the units switched to the another antiseptic agent with a 2-week washout period. This alternating skin disinfection method was carried out until the study groups used all four antiseptic agents. Blood specimens were incubated for seven days unless the ordering physician requested longer incubation. Standard aerobic and anaerobic bottles were processed by the microbiology lab according to standard protocol using BacTAlert. Positive cultures were further subcultured and processed using standard laboratory techniques. The physician investigator reviewed the positive cultures and classified them as true positive or as contaminated. A culture was considered contaminated if a common skin organism was isolated from only one of two blood samples obtained from different sites, i.e., coagulase-negative Staphylococcus, Micrococcus spp., Bacillus spp., Propionibacterium acnes (currently Cutibacterium acnes), viridans streptococci, or Corynebacterium spp.. In total of 12,806 blood culture samples were collected during the study period. The study did not report on the number of patients from whom blood cultures were collected.

Mimoz (1999) conducted a randomized controlled trial to evaluate the effectiveness of PI and CHG on blood culture contamination rates. The study was carried out in three adult intensive care units at a French teaching hospital between 1 December 1997 and 24 April 1998. Blood culture samples were drawn by nurses. Both antiseptic agents were applied vigorously and allowed to dry for 15 to 30 s after application. The blood samples were simultaneously inoculated into aerobic and anaerobic vials of blood culture media. The cultures were incubated at 37^OC for five days, and standard methods and criteria were used to isolate organisms and their susceptibilities. Contaminant isolates were defined as isolates of several organisms obtained from one set of blood cultures and identical organism that was not obtained from ananother potentially infected site five days before or five days after blood culture collection. Several organisms considered as a contaminant were coagulase-negative Staphylococci, Propionibacterium acnes (currently Cutibacterium acnes), Streptococcus spp. (viridans group), Corynebacterium spp. (excluding group JK), Micrococcus spp., or Bacillus spp.. During the study, a total of 2041 blood culture samples were collected from 403 patients. The study did not report whether nurses who collected the blood samples were trained in technique.

Little (1999) conducted a randomized controlled trial to evaluate the effectiveness of PI and IT on blood culture contamination rates. The study was carried out in adult inpatients units at an American tertiary care teaching hospital between December 1, 1995, and July 31, 1991. Blood culture samples were drawn by trained experienced phlebotomists. Patients in whom the skin was disinfected with PI were first treated with IPA gauze pad for one min. Patients in whom the skin was disinfected with IT were first scrubbed with a 70% IPA applicator for 1 min before applying the iodine tincture. Both antiseptic agents were allowed to dry for 2 min prior to venepuncture. A needle change methodology was not utilized. Blood culture samples were processed using BACTEC 9240. Blood culture sets included one bottle each of aerobic/F and aerobic/F Plus (a resin-containing bottle) BACTEC soybean-casein digest media. All culture sets were incubated until growth was detected, or for a total of seven days. A positive culture was considered contaminated if it yielded growth of Corynebacterium spp., Propionibacterium spp., Clostridium spp., Micrococcus spp. or Bacillus spp., coagulase-negative Staphylococci, or Acinetobacter baumannii in one or both bottles without isolation of the same organism from ananother blood culture sample of ananother site culture. For comparison, also data were included on the total blood culture contamination rate (not just skin flora) using the criteria of MacGregror and Beaty. In the study, a total of 3,851 blood culture samples were collected from 1,503 patients. The concentration of the IPA gauze pad used prior to PI was not reported as well as information was lacking on difference in contamination rates between ER and ICU.

Results

Sub-question 1 Skin disinfection venous blood sampling

Not applicable

Sub-question 2 Skin disinfection injection

Local or systemic infection

Wong (2019) found no local or systemic infections among the participants both in the intervention group and control group. Each group consisted of 85 children. The participants in the intervention group received 142 vaccinations in total; 119 vaccinations administered intramuscularly and 23 vaccinations subcutaneously. Participants in the control group received 137 vaccinations in total; 118 administered intramuscularly and 19 vaccinations subcutaneously. There was a difference in loss to follow-up between both groups due to missing telephone survey or diary data, 14 and 18 patients, respectively. Reasons for this were not reported. Seven participants had one or two local skin reactions on Day 5 and were invited to return to the clinic. Only one patient returned to the pediatrician from which the diagnosis was injection site swelling. No aspiration of the injection site was done.

The two observational studies, (Khawaja, 2013; Koivisto, 1978) found no local or systemic infection among the participants both in the intervention and control group.

Sub-question 3 Skin antiseptic agents venous blood sampling and injection

Infection

No studies were found.

Side effects

No studies were found.

Blood culture contamination

1. Comparison of alcoholic products versus non-alcohol products in studies using a 1-step method of skin disinfection
   Three studies compared alcoholic products with non-alcohol products using a 1-step method of skin disinfection. Mimoz (1999) found 34 (34/1022) contaminated blood cultures in the PI group compared to 14 (14/1019) in the CHG group. Suwanpimolkul (2008) found 34 (34/1068) contaminated blood cultures in the CHG group compared to 74 (74/1078) in the PI group. The pooled RR was 0.45 [95%CI: 0.32 – 0.63] in favor of the use of an alcoholic product. This is a clinically relevant difference.
   Calfee (2002) found 99 (99/3,378) contaminated blood cultures in the PI group compared to 81 (81/3,138) in the IT group, 78 (78/3,125) in the IPA group, and 75 (75/3,051) in the Persist group. The RR was 0.86 [95%CI: 0.68 – 1.08] in favor of the use of an alcoholic product. This is not a clinically relevant difference.
2. Comparison of alcoholic products in the first and second step of skin disinfection versus only alcoholic product in the first disinfection step (studies using a 2-steps method of skin disinfection)
   Two studies compared alcoholic products used in the first and second step of a 2-step method of skin disinfection versus only an alcoholic product in the first disinfection step. Washer (2013) found 25 (25/4,286) contaminated blood cultures in the IPA/PI group compared to 32 (32/4,230) in the IPA/IT group. The RR was 1.30 [95%CI: 0.77 – 2.18] in favor of the use of only an alcoholic product in the first disinfection step. This is a clinically relevant difference. Little (1999) found 74 (74/1947) contaminated blood cultures in the IPA/PI compared to 46 (46/1904) in the IPA/IT group. The RR was 0.64 [95%CI: 0.44 – 0.91] in favor of the use of alcoholic products used in the first and second disinfection step. This is a clinically relevant difference.
3. Comparison of chlorhexidine gluconate versus another alcoholic products in the second disinfection step (studies using a 2-steps method of skin disinfection; first step involving skin disinfection using an alcoholic product in both groups)
   Two studies compared CHG with another alcoholic products in the second disinfection step using a 2-steps method of skin disinfection. In both studies an alcoholic product was used in the first disinfection step. Martinez (2017) found a blood contamination rate of 0.9% (5/563) in patients where the skin of patients was first disinfected with IPA, followed by a 30 s drying time before being disinfected again with alcohol. Patients from whom the skin was first disinfected with IPA, followed by a 30 s drying time before being disinfected with CHG, the blood contamination rate was 1.7% (10/539). Story-Roller (2016) found a blood contamination rate of 3.93% (123/3130) where the skin of patients was first disinfected with IPA, followed by a 30 s drying time before being disinfected with IT. Patients from whom the skin was first disinfected with IPA, followed by a 30 s time before being disinfected with CHG, the blood contamination rate was 3.88% (115/2965). We calculated a pooled risk ratio (RR) for the two studies. The pooled RR was 1.19 [95%CI: 0.63 – 2.25] in favor of the use of another alcoholic product, with moderate heterogeneity (I² = 44%). This is not a clinically relevant difference.

Level of evidence of the literature

Sub-question 1 Skin disinfection venous blood sampling

Not applicable

Sub-question 2 Skin disinfection injection

It was not possible to grade the evidence of skin disinfection prior to intramuscular, subcutaneous, or intradermal injection on the occurrence of local or systemic infections. The absence of events in the studies could be attributed to the low number of included patients (power) or the follow-up duration (too short).

Sub-question 3 Skin antiseptic agents venous blood sampling and injection

Infection

The level of evidence could not be assessed for the outcome measure infection, because no studies were found.

Side effects

The level of evidence could not be assessed for the outcome measure side effects, because no studies were found.

Blood culture contamination

The level of evidence was assessed for the outcome measure blood culture contamination:

1. Comparison of alcoholic products versus non-alcohol products in studies using a 1-step method of skin disinfection
   The level of evidence regarding the outcome measure blood culture contamination started at high and was downgraded by two levels to low because of study limitations (-1; risk of bias: randomisation process unclear, no blinding of healthcare workers), imprecision (-1: confidence interval overlaps threshold for minimal clinically important difference).
2. Comparison of alcoholic products in the first and second step of skin disinfection versus only an alcoholic product in the first disinfection step (studies using a 2-steps method of skin disinfection)
   The level of evidence regarding the outcome measure blood culture contamination started at high and was downgraded by three levels to very low because of study limitations (-1; risk of bias: no blinding of healthcare workers, another problems mentioned in table risk of bias), inconsistency (-1, results are contradictory), imprecision (-1: confidence interval overlaps threshold for minimal clinically important difference).
3. Comparison of chlorhexidine gluconate versus another alcoholic products in the second disinfection step (studies using a 2-steps method of skin disinfection; first step involving skin disinfection using an alcoholic product in both groups)
   The level of evidence regarding the outcome measure blood culture contamination started at high and was downgraded by 3 levels to very low because of study limitations (-1; risk of bias: randomisation process unclear, no blinding of healthcare workers and outcome assessors, another problems), and imprecision (-2: confidence interval overlaps both thresholds for minimal clinically important difference).

Sub-question 1 Skin disinfection venous blood sampling

No conclusions could be drawn because of the absence of relevant studies.

Sub-question 2 Skin disinfection injection

It was not possible to grade the evidence of skin disinfection prior to intramuscular, subcutaneous, or intradermal injection on the occurrence of local or systemic infections. The absence of events in the studies could be attributed to the low number of included patients (power) or the follow-up duration (too short).

Sub-question 3 Skin antiseptic agents venous blood sampling and injection

Infection

Side effects

Blood culture contamination

1. Comparison of alcoholic products versus non-alcohol products in studies using a 1-step method of skin disinfection

2. Comparison of alcoholic products in the first and second step of skin disinfection versus only alcoholic product in the first disinfection step (studies using a 2-steps method of skin disinfection)

3. Comparison of chlorhexidine gluconate versus another alcoholic products in the second disinfection step (studies using a 2-steps method of skin disinfection; first step involving skin disinfection using an alcoholic product in both groups).

WHO Guidelines on Drawing Blood: Best Practices in Phlebotomy. Geneva: World Health Organization; 2010. PMID: 23741774.

Khawaja, R. A. and Sikanda, R. and Qureshi, R. and Jareno, R. J. M. Routine skin preparation with 70% isopropyl alcohol swab: Is it necessary before an injection? Quasi study. Journal of the Liaquat University of Medical and Health Sciences. 2013; 12 (2) :109-114.

Koivisto VA, Felig P. Is skin preparation necessary before insulin injection? Lancet. 1978 May 20;1(8073):1072-5. doi: 10.1016/s0140-6736(78)90916-9. PMID: 77369.

Wong H, Moss C, Moss SM, Shah V, Halperin SA, Ito S, Mithal P, Qu A, Taddio A. Effect of alcohol skin cleansing on vaccination-associated infections and local skin reactions: a randomized controlled trial. Hum Vaccin Immunother. 2019;15(4):995-1002. doi: 10.1080/21645515.2018.1553474. Epub 2019 Jan 16. PMID: 30513266; PMCID: PMC6605859.

Bekijk de Evidence-tabellen:

Evidence-tabellen

Sub-question 1 Skin disinfection venous blood sampling

Sub-question 2 Skin disinfection injection

Sub-question 3 Skin antiseptic agents venous blood sampling and injection

Systematic reviews and randomised controlled trials

Observational studies

Bekijk de Risk-of-bias-tabel:

Risk-of-bias-tabel

Werkwijze

AGREE

Deze richtlijnmodule is opgesteld volgens de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).

Knelpuntenanalyse en uitgangsvragen

Tijdens de voorbereidende fase inventariseerde de werkgroep de knelpunten in de zorg voor patiënten waarbij de huid wordt gedesinfecteerd voorafgaand aan een ingreep, punctie/biopsie en injectie. De werkgroep beoordeelde de aanbeveling(en) uit de eerdere WIP-richtlijnen Desinfectie huid en slijmvliezen en Puncties op noodzaak tot revisie. Tevens zijn er knelpunten aangedragen door IGJ, KNMP, NAPA Nederlandse Associatie Physician Assistants (Nederlandse Associatie Physician Assistants ), NOG Nederlands Oogheelkundig Gezelschap (Nederlands Oogheelkundig Gezelschap ), NVAB Nederlandse Vereniging voor Arbeids- en Bedrijfsgeneeskunde (Nederlandse Vereniging voor Arbeids- en Bedrijfsgeneeskunde ), NVALT Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose ), NVvC, NVDV Nederlandse Vereniging voor Dermatologie en Venereologie&nbsp; (Nederlandse Vereniging voor Dermatologie en Venereologie&nbsp; ), NVIC, NVK, NVKC, NVKF Nederlandse Vereniging voor Klinische Fysica (Nederlandse Vereniging voor Klinische Fysica ), NVKG, NVMM Nederlandse Vereniging voor Medische Microbiologie (Nederlandse Vereniging voor Medische Microbiologie ), NVPC, NVU, NVvA Nederlandse Vereniging voor Arbeidshygiëne (Nederlandse Vereniging voor Arbeidshygiëne ), NVR, NVvR Nederlandse Vereniging voor Radiologie (Nederlandse Vereniging voor Radiologie ), NVZ, NVZA Nederlandse Vereniging van Ziekenhuisapothekers (Nederlandse Vereniging van Ziekenhuisapothekers ), SNV, VCCN, VDSMH Vereniging Deskundigen Steriele Medische Hulpmiddelen (Vereniging Deskundigen Steriele Medische Hulpmiddelen ), Verenso Vereniging van specialisten ouderengeneeskunde (Vereniging van specialisten ouderengeneeskunde ) en VHIG Vereniging voor Hygiëne en Infectiepreventie in de Gezondheidszorg (Vereniging voor Hygiëne en Infectiepreventie in de Gezondheidszorg ) via een schriftelijke knelpunteninventarisatie. Een verslag hiervan is opgenomen onder aanverwante producten.

Op basis van de uitkomsten van de knelpuntenanalyse zijn door de werkgroep concept-uitgangsvragen opgesteld en definitief vastgesteld.

Uitkomstmaten

Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde de werkgroep welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. De werkgroep waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Ook definieerde de werkgroep tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.

Methode literatuursamenvatting

Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder Zoeken en selecteren onder Onderbouwing. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. Review Manager 5.4 werd gebruikt voor de statistische analyses. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.

Beoordelen van de kracht van het wetenschappelijke bewijs

De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE Grading Recommendations Assessment, Development and Evaluation (Grading Recommendations Assessment, Development and Evaluation )-methode. GRADE staat voor Grading Recommendations Assessment, Development and Evaluation (zie www.gradeworkinggroup.org). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding).

GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).

Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in richtlijnen volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet een-op-een vergelijkbaar met het minimaal klinisch relevant verschil (minimal clinically important difference (MCID Minimal Clinically Important Difference (Minimal Clinically Important Difference ))). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming over de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).

Overwegingen (van bewijs naar aanbeveling)

Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje Overwegingen en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision-framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision-framework is een integraal onderdeel van de GRADE-methodiek.

Formuleren van aanbevelingen

De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. De kracht van het wetenschappelijk bewijs en het gewicht dat door de werkgroep wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Volgens de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. De werkgroep heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.

In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE-gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.

Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers

Organisatie van zorg

In de knelpuntenanalyse en bij de ontwikkeling van de richtlijnmodule is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, menskracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in de module Organisatie van zorg.

Commentaar- en autorisatiefase

De conceptrichtlijnmodule werd aan de betrokken (wetenschappelijke) verenigingen en (patiënten) organisaties voorgelegd ter commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijnmodule aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijnmodule werd aan de deelnemende (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd voor autorisatie en door hen geautoriseerd dan wel geaccordeerd.

Inbreng patiëntenperspectief

Er werd aandacht besteed aan het patiëntenperspectief door uitnodigen van Patiëntfederatie Nederland (PFNL Patiëntfederatie Nederland (Patiëntfederatie Nederland )) voor de schriftelijke knelpuntenanalyse. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptrichtlijn is ook voor commentaar voorgelegd aan PFNL en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.

Wkkgz Wet kwaliteit, klachten en geschillen zorg (Wet kwaliteit, klachten en geschillen zorg ) & Kwalitatieve raming van mogelijke substantiële financiële gevolgen

Bij de richtlijn is in overeenstemming met de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling zijn richtlijnmodules op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).

Uit de kwalitatieve raming blijkt dat er waarschijnlijk geen substantiële financiële gevolgen zijn, zie onderstaande tabel.

Literatuur

Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for  strong recommendations: an analytical survey. BMJ Open. 2017 Nov 16;7(11):e018593. doi: 10.1136/bmjopen-2017-018593. PubMed PMID: 29150475; PubMed Central PMCID: PMC5701989.

Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016 Jun 28;353:i2016. doi: 10.1136/bmj.i2016. PubMed PMID: 27353417.

Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089. doi: 10.1136/bmj.i2089. PubMed PMID: 27365494.

Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in healthcare. CMAJ. 2010 Dec 14;182(18):E839-42. doi: 10.1503/cmaj.090449. Epub 2010 Jul 5. Review. PubMed PMID: 20603348; PubMed Central PMCID: PMC3001530.

Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13. doi: 10.1016/j.jclinepi.2017.05.006. Epub 2017 May 18. PubMed PMID: 28529184; PubMed Central PMCID: PMC6542664.

Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwaliteit.

Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.

Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013.

Tijdens de ontwikkeling van de richtlijn Desinfectie huid en slijmvliezen plus puncties is systematisch gezocht naar onderzoeksbevindingen die nuttig konden zijn voor het beantwoorden van de uitgangsvragen. Een deel (of een onderdeel) van de hiervoor opgestelde zoekvragen is met het resultaat van deze zoekacties te beantwoorden, een deel echter niet. Door gebruik te maken van de evidence-based methodiek (EBRO Evidence Based Richtlijn Ontwikkeling (Evidence Based Richtlijn Ontwikkeling )) is duidelijk geworden dat er nog kennislacunes bestaan. De werkgroep is van mening dat (vervolg)onderzoek wenselijk is om in de toekomst een duidelijker antwoord te kunnen geven op vragen uit de praktijk. Om deze reden heeft de werkgroep per module aangegeven waar wetenschappelijke kennis beperkt is en dus op welke vlakken nader onderzoek gewenst is.

Module 1 Huiddesinfectie

Module 1.1 Huiddesinfectie ingrepen algemeen

Geen systematische search uitgevoerd.

Module 1.2 Bloedafname en injectie

Het is onduidelijk wat de plaats is van huiddesinfectie voorafgaand aan bloedafname ten behoeve van diagnostiek en keuringen op het voorkómen van een (lokale/systemische) infectie bij de patiënt?
Het is onduidelijk wat de plaats is van huiddesinfectie voorafgaand aan een intramusculaire, subcutane of intradermale injectie op het voorkómen van een infectie bij de patiënt?
Het is onduidelijk welk huiddesinfectiemiddel de voorkeur heeft om voorafgaand aan een bloedafname en/of een injectie (intramusculair, subcutaan, intradermaal) te gebruiken, om een infectie bij de patiënt te voorkómen en in geval van bloedafname het risico op contaminatie van het bloedmonster te reduceren? Echter de werkgroep is van mening dat de praktijk hierdoor niet gehinderd wordt en voert deze daarom niet als kennislacune op.

Module 1.3 Hoofd-halsgebied en oog

Er is onvoldoende bewijs over de optimale concentratie van povidonjodium voor desinfectie van het oogoppervlak.

Module 1.4 Prematuren/neonaten

Tot op heden is de vraag welk huiddesinfectiemiddel effectief en het meest veilig is in gebruik bij prematuren en neonaten niet uitgebreid onderzocht.

Module 2. Algemene voorzorgsmaatregelen Punctie/biopsie/injectie

Module 2.1 Punctie/biopsie/injectie

Bij nieuwe ontwikkelingen/interventies in de gezondheidszorg, waaronder puncties, zal op basis van best practices een keuze gemaakt worden over de te treffen infectiepreventiemaatregelen in overleg met de behandelaar. De werkgroep is van mening dat (vervolg)onderzoek wenselijk is om in de toekomst een duidelijker antwoord te kunnen geven op de noodzaak voor welke maatregelen uit het oogpunt van infectiepreventie nodig zijn en in het kader van de Greendeal niet onnodig getroffen worden.

Module 2.2 Intra-articulaire injectie

Wat is het effect van infectiepreventiemaatregelen op het ontstaan van zorggerelateerde infecties na een intra-articulaire injectie of punctie?

Overig/toekomstige knelpunten

Er is tot nu toe onvoldoende bekend over de aspecten voor duurzaamheid in relatie tot de voorkeur voor een bepaald desinfectiemiddel.

Bekijk  de pdf met het overzicht van de ontvangen reacties voor een schriftelijke knelpuntenanalyse voor deze richtlijn.

Rapportage knelpunteninventarisatie