V. Damjanovic

How to classify infections in intensive care units-the carrier state, a criterion whose time has come?

Gram’s staining technique, discovered in 1883, is still the unchallenged criterion for the classification of micro-organisms causing infections in intensive care units (ICU). The recent European prevalence of study of infection in ICU (EPIC) revealed that the bacterial isolates were almost equally divided between Gram-negative and Gram-positive organisms.’ The definitions of the Centers for Disease Control and Prevention (CDC) issued in 1988 are generally accepted as the ‘gold’ standard for the classification of ICU-infections. A hospital-acquired infection is one for which there is no evidence that the infection was present or incubating at the time of hospital admission.* These CDC criteria were applied in the EPIC-study to distinguish three types of ICU infection. First, community-acquired-an infection occurring in the community and manifest on admission to the ICU; second, hospitalacquired-an infection manifest on admission to the ICU in a patient who was hospitalized in another hospital or ward; and third, ICU-acquired-an infection having originated in the ICU but not clinically manifest at the time of admission to the ICU.’ Although no specific time is given by the CDC to determine whether an infection is community, hospital, or ICUacquired, arbitrary 48 h, 72 h, 96 h, and even 120 h cut-off points are used by different groups to distinguish between the two.“’ An in-vitro staining method and a variable time cut-off are thus the traditional bases for microbiology in the ICI-J. However, these criteria may not be helpful for the patient requiring intensive care. For example, a South

Selective decontamination with nystatin for control of a Candida outbreak in a neonatal intensive care unit.

Selective decontamination of the digestive tract (SDD) with oral nystatin was evaluated as a measure to control an outbreak of Candida infection in a neonatal intensive care unit (NICU). Seventy-six out of 106 neonates who carried Candida spp. received the main study manoeuvre (the application of oral nystatin in the throat and stomach) during the 12-month open trial. One third of the neonates weighed < 1500 g whilst about half were being ventilated. The mean stay was 33.2 d (SD +/- 46.9). Two cases with candidaemia within a fortnight were associated with a yeast carriage rate in the NICU of about 50%; more than 80% of the isolates were Candida parapsilosis. During the implementation period there were four new neonates with fungaemia caused by C. parapsilosis. Once the carriage rate dropped below 5% (P < 0.001), no new cases of systemic infection with the outbreak strain were recognized in the following 8 months. It took 3.5 months to control the outbreak. The observation that all other clinical diagnostic samples were free from Candida suggests that translocation from throat or gut into the systemic circulation occurred. SDD with oral nystatin was effective in reducing the yeast carriage index (mean index 1.93, before SDD; 0.45, after SDD; P < 0.001). A significant reduction of carriage, both in rates and indices, is thought to have contributed to the control of this candida outbreak.

Microbial Gut Overgrowth Guarantees Increased Spontaneous Mutation Leading to Polyclonality and Antibiotic Resistance in the Critically Ill

Polyclonality is defined as the occurrence of different genotypes of a bacterial species. We are of the opinion that these different clones originate within the patient. When infections and outbreaks occur, the terms of polyclonal infections and polyclonal outbreaks have been used, respectively. The origin of polyclonality has never been reported, although some authors suggest the acquisition of different clones from different animate and inanimate sources. We think that the gut of the critically ill patient with microbial overgrowth is the ideal site for the de-novo development of new clones, following increased spontaneous mutation.

Selective decontamination of the digestive tract: selectivity is not required

Dear Editor, We read Benus and colleagues’ article entitled ‘Impact of digestive and oropharyngeal decontamination on the intestinal microbrota in ICU patients’ [1]. Benus tested the hypothesis that selective decontamination of the digestive tract (SDD) may achieve its claimed benefits by leaving the anaerobic intestinal microbiota unaffected, which indicates a misunderstanding of SDD [2]. SDD was designed based on the observation that critical illness changes flora. Critical illness promotes a shift from normal (S. pneumoniae in the throat and E. coli in the gut) towards abnormal carriage (aerobic Gram-negative bacilli and methicillin-resistant Staphylococcus aureus) and overgrowth of both. Parenteral cefotaxime controls overgrowth of ‘normal’ flora, whereas abnormal flora is controlled by enteral polymyxin/tobramycin. There are 60 randomised controlled trials (RCT) and 10 meta-analyses confirming that SDD reduces pneumonia (72%), septicaemia (37%) and mortality (29%) without resistance emerging. Benus’s article focuses on ‘selectivity’. Anaerobes rarely cause infections; instead, the indigenous anaerobic flora contributes to physiology and control of abnormal carriage, i.e. it promotes colonisation resistance (CR) [3]. Antimicrobials suppressing anaerobes are ‘non-selective’, those leaving them virtually intact are ‘selective’. Using fluorescent in situ hybridization, Benus demonstrates that SDD impacts the indigenous flora, particularly Faecalibacterium prausnitzii, an anaerobic Gram-negative bacillus significantly reduced by high faecal tobramycin levels. They hypothesize that F. prausnitzii plays a role in maintaining CR, therefore SDD cannot be beneficial by leaving colonic microbiota unaffected. Interestingly, the faecal samples studied by Benus were collected from ICU patients enrolled in a recent RCT showing efficacy and safety of SDD [1]. The only conclusion is that SDD is effective and safe although not selective, as described by Vollaard et al. [3]. Donskey [4] wrote that SDD has tremendous potential although it is not truly selective. Six healthy volunteers were challenged with cefotaxime-resistant Enterobacter cloacae after intravenous administration of cefotaxime [3]. All became carriers, five experienced overgrowth, and all cleared the strain during pre-treatment without cefotaxime. Parenteral cefotaxime was chosen for SDD [2] as it has been shown to control overgrowth of normal flora through its high salivary and biliary concentrations. These levels are also bactericidal against Clostridium species, Gram-positive bacilli amongst the indigenous anaerobes, and are thought to contribute to CR [5]. Benus assessed the impact of SDD on CR in 17 ICU patients and reports a significant reduction in F. prausnitzii, which is hypothesized to play a role in maintaining CR, in contrast to Wensinck who showed that CR is based on anaerobic Gram-positive Clostridium species. Hence, Benus concludes that SDD is not selective. Benus fails to acknowledge Vollaard’s and Donskey’s work, although both are relevant to the assertion that SDD is a contradiction in terms, i.e., effective decontamination or eradication of gut overgrowth whilst maintaining complete selectivity does not make sense. However, the originators of SDD have always been aware of this contradiction in terms [2] preferring effectivity over selectivity, if negative consequences of non-selectivity are neutralised by enteral antimicrobials (polymyxin/tobramycin/amphotericin B). In conclusion, SDD exerts benefits via antimicrobial concentrations effective against overgrowth of normal and abnormal flora rather than by sparing the CR flora. The clinical impact of F. prausnitzii reduction in the critically ill is unclear.

For control of colonisation with extended-spectrum β-lactamase-producing bacteria, SDD does work

Dear Editor, We read with interest the French report entitled ‘‘Clinical impact and risk factors for colonization with extended-spectrum b-lactamase-producing bacteria in the intensive care unit’’ [1] as we are aware that these researchers have previously reported on this topic. Brun-Buisson et al. [2] have an understanding of endemicity and outbreaks of carriage and infection due to extended-spectrum betalactamase-producing Enterobacteriaceae (ESBL-PE). In 1989, they described an outbreak of carriage and infection due to ESBL-producing Klebsiella pneumoniae. Carriage and infection rates were 20 and 10 %, respectively. Reinforcement of hygiene practices failed to control the outbreak until they introduced a form of selective decontamination of the digestive tract (SDD) using enteral antimicrobials aimed at the eradication of carriage of the outbreak strain. The enteral antimicrobial cocktail applied included polymyxin E, neomycin and nalidixic acid. The carriage and infection rates dropped to 3 and 0 %, respectively. In a later study by other authors enteral antimicrobials were shown to significantly reduce absolute carriage, a more appropriate term for colonisation pressure [3]. Colonisation pressure is qualitatively defined as the proportion of patients who carry the outbreak strain (percentage) in the ICU, whilst absolute carriage also takes into account the level of carriage of the outbreak strain in the ICU (qualitatively and quantitatively). It is puzzling to us why 23 years later, Brun-Buisson et al. overlooked the one intervention that does work for the control of endemicity and outbreaks of ESBL-PE [4] when writing in their recent report that ‘our data suggest that additional measures may be warranted to control the spread of the latter species’ [1]. Abecasis et al. [4] recommend the more up-to-date enteral combination of polymyxin E and tobramycin. This positive experience comes from a paediatric ICU with a different setting, patient population and epidemiology compared with the Parisian ICU. However, we believe that SDD is worth trying as the combination of polymyxin E and tobramycin covers both community and ICU-associated ESBL-PEs such as E. coli, E. cloacae and K. pneumoniae, the three different strains described by another French group [5]. Finally, improving carbapenem use is a major challenge for Parisian intensivists. In contrast, the 25-year experience with SDD has demonstrated that the addition of enteral antimicrobials (polymyxin/tobramycin) to parenteral antimicrobials such as cefotaxime and carbapenems has prolonged the antibiotic era of these useful systemic agents, as the essential component of SDD (i.e., the enteral antibiotics) controls gut overgrowth of E. coli, E. cloacae and K. pneumoniae, the major risk factor for de novo development of resistance. References

Origin of epidemic clones of acinetobacter in the critically ill.

contaminated by microbes from a clinician’s coat by direct contact or by airborne spread serving as a new source for contamination. Transmission of micro-organisms from white uniforms has been considered as a source of transfer from nurses’ gowns to patients and bed sheets. In this report, the transfer of bacteria from uniform fabrics to another surface is poorly influenced by the humidity of the fabric, although there were statistical differences between recoveries of different bacteria after transfer from a wet or a dry fabric surface. The most likely reason is the very low survival of bacteria on the fabric during the first minute. Desiccation plays a major role in survival of bacteria and transfer from surfaces. Despite the low numbers of surviving cells, transmission of the tested pathogens remains possible. Whether this will actually lead to infection is unknown, since the minimum infective dose of the micro-organisms tested in the present study is influenced by many factors, such as route and site of inoculum, and immunity of the host.

Selective digestive decontamination and Enterococcus faecalis overgrowth and infection: a robust relation is yet unproven.

To the Editor We read with interest the article by Muruz abalLecumberri et al. (1). The authors described the presence and dissemination in the intensive care unit (ICU) of a specific Enterococcus faecalis clone, ST6 (CC2). They concluded that this event could be related to the use of selective digestive decontamination (SDD), which included oropharyngeal and intestinal gentamicin, polymyxin E and amphotericin B associated with a 3-day course of parenteral ceftriaxone. We believe that their statement is not robust due to limitations in the study design. The study included 200 patients, and in 46 of them E. faecalis was isolated. Only 24 E. faecalis isolates, which were collected mainly from bronchial samples, were the basis of the study. However, the authors did not mention the time at which the samples were obtained. The isolation of E. faecalis in patients on their ICU admission, either from the community or from other hospitals/wards, may have nothing to do with the subsequent use of SDD during ICU treatment. The presence of E. faecalis ST6 (CC2) clones showing gentamicin resistance has been reported in high percentages in the community in Spain (2), as well as in other countries (3). Therefore, intestinal carriage or infection due to this microorganism can be imported in the ICU from the community. The study was not designed to test the hypothesis that SDD may cause overgrowth and infection due to E. faecalis clones. However, the authors reported, only in the discussion section, a rise in enterococcal colonization and infection after SDD, and an increase in E. faecalis isolates, from 10.6% of all isolates before SDD to 27.9% during SDD. The authors associated this increase to the SDD components, namely parenteral ceftriaxone and topical gentamicin. This statement is not robust as there may be several other reasons justifying this observation. First, the increase in percentages of isolates of enterococci may be simply due to their isolation in surveillance cultures of rectal swabs, a manoeuvre uncommon in patients not receiving SDD. Second, the authors did not report any data on the concurrent use of parenteral antibiotics, in particular those associated with enterococcal overgrowth and/or infection (4–6). Third, the change in local epidemiology of E. faecalis is crucial. This, again, emphasizes the importance of the distinction between imported and acquired enterococcal strains in the ICU. Therefore, the ideal study should be randomized, comparing SDD with placebo or standard care, and should also focus on oropharyngeal and gut carriage rather than on only diagnostic samples of lower airways, urine and blood. Interestingly, the literature on the impact of SDD on resistant enterococci is predominantly restricted to the emergence of vancomycin-resistant enterococci (VRE). A recent meta-analysis showed that in the only 5 SDD studies reporting these data and including 4851 patients, there was a 37% nonsignificant reduction of VRE in SDD patients compared with controls (odds ratio 0.63, 95% confidence interval 0.39–1.02) (7). In conclusion, although the authors affirm that the presence of ST6 (CC2) clone ‘could be related to the use of SDD’, indicating some uncertainty from their point of view, they should acknowledge that a solid link between SDD and colonization/infection by ST6 (CC2) E. faecalis clone cannot be demonstrated in their study.

Outbreaks of Infection in the ICU: What’s up at the Beginning of the Twenty-First Century?

Surveillance cultures are the only cultures that allow the distinction between secondary endogenous and exogenous infections. These types of infection are the two known to cause outbreaks. Secondary endogenous infections can be controlled by enterally administered antimicrobials and should be integrated into the routine infection control measures. Exogenous infections can be controlled by topically applied antimicrobials and hygiene.