Less Is More: When to Repeat Antimicrobial Susceptibility Testing.

This study investigated the frequency of change of the antimicrobial susceptibility pattern when the same isolate was found in the same patient in various situations. We used laboratory data collected over a period of 8 years (January 2014 to December 2021) at the clinical microbiology laboratory of a tertiary hospital for Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Staphylococcus aureus. Antimicrobial susceptibility tests (AST) were performed using Vitek 2 automated system. We determined essential agreement and categorical agreement, and introduced the new terms essential MIC increase and change from nonresistant to resistant to present changes in antimicrobial susceptibility over time. During the study period, 18,501 successive AST were included. The risk for S. aureus to be resistant to any antibiotic upon repeated culture was <10% during a follow-up of 30 days. For Enterobacterales, this risk was approximately 10% during a follow-up of 7 days. For P. aeruginosa, this risk was higher. The longer the follow-up period, the higher the risk that the bacteria would show phenotypic resistance. We also found that some drug-bug combinations were more likely to develop phenotypical resistance (i.e., E. coli/amoxicillin-clavulanic acid and E. coli/cefuroxime). A potential consequence of our finding is that if we regard a risk of resistance below 10% as acceptable, it may be feasible to omit follow-up AST within 7 days for the microorganisms investigated in this study. This approach saves money, time, and will reduce laboratory waste. Further studies are needed to determine whether these savings are in balance with the small possibility of treating patients with inadequate antibiotics.

The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy.

OBJECTIVES: Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy. METHODS: The guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak. RESULTS: Sixty recommendations were provided for suspected allergy to ß-lactam antibiotics (BLAs) and non-ß-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team. CONCLUSIONS: Accumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non-ß-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.

Limiting spread of VIM-positive Pseudomonas aeruginosa from colonized sink drains in a tertiary care hospital: A before-and-after study.

BACKGROUND: In healthcare environments, sinks are being increasingly recognized as reservoirs for multidrug-resistant Gram-negative bacteria. In our hospital, carbapenemase-producing, Verona Integron-encoded Metallo-beta-lactamase (VIM)-positive Pseudomonas aeruginosa (VIM-PA) was detected at low endemicity in patients, and environmental culturing revealed that sink drains were primary reservoirs. Therefore, an intervention was initiated in several wards to install sink drain plugs as physical barriers against splashing to prevent transmission of VIM-PA from drain reservoirs to the surrounding sink environment. AIM: To assess the efficacy of the intervention on limiting spread of VIM-PA. METHODS: Swabs were taken from inner sink environments (i.e. drains), and outer sink environments (i.e. wash basins, faucet aerators, and countertops) twice before and three times after the intervention. Siphon water and drain wells were also sampled before and at the moment of the intervention, respectively. All samples were screened for VIM-PA, and isolates were typed with multiple-locus variable-number tandem repeat analysis (MLVA). RESULTS: There was a significant reduction in VIM-PA positivity in both inner (P-value <0.001) and outer (P-value 0.001) sink environments after the intervention. However, VIM-PA recolonization was observed in the inner sink environments of patient rooms, and also in rooms exclusive to healthcare personnel, over time. Surfaces in the outer sink environment were rarely positive for VIM-PA after the intervention. MLVA revealed three genetic clusters, with one found in all wards and room types during the study period. CONCLUSIONS: Drain plugs are a simple and effective infection prevention and control measure to contain spread of VIM-PA from drain reservoirs.

Microcalorimetry: A Novel Application to Measure In Vitro Phage Susceptibility of Staphylococcus aureus in Human Serum.

Infections involving antibiotic resistant Staphylococcus aureus (S. aureus) represent a major challenge to successful treatment. Further, although bacteriophages (phages) could be an alternative to antibiotics, there exists a lack of correlation in phage susceptibility results between conventional in vitro and in vivo assays. This discrepancy may hinder the potential implementation of bacteriophage therapy. In this study, the susceptibility of twelve S. aureus strains to three commercial phage cocktails and two single phages was assessed. These S. aureus strains (including ten clinical isolates, five of which were methicillin-resistant) were compared using four assays: the spot test, efficiency of plating (EOP), the optical density assay (all in culture media) and microcalorimetry in human serum. In the spot test, EOP and optical density assay, all cocktails and single phages lysed both methicillin susceptible and methicillin resistant S. aureus strains. However, there was an absence of phage-mediated lysis in high concentrations of human serum as measured using microcalorimetry. As this microcalorimetry-based assay more closely resembles in vivo conditions, we propose that microcalorimetry could be included as a useful addition to conventional assays, thereby facilitating more accurate predictions of the in vivo susceptibility of S. aureus to phages during phage selection for therapeutic purposes.

Characterization of Staphylococcus roterodami sp. nov., a new species within the Staphylococcus aureus complex isolated from a human foot infection.

This article introduces a new Staphylococcus species cultivated from a human foot wound infection in a Dutch traveller returning from the island of Bali, Indonesia: Staphylococcus roterodami sp. nov. Based on the genomic sequence, there is strong molecular evidence for assigning the strain to a novel species within the S. aureus complex. Differences in cellular fatty acid spectrum and biochemical tests underline these findings. Its ecological niche and pathogenicity require further study. The type strain is DSM111914T (JCM34415T).

Warm Weather and Surgical Site Infections: A Meta-analysis.

Seasonal variability, in terms of warm weather, has been demonstrated to be a significant risk factor for surgical site infections (SSIs). However, this remains an underexposed risk factor for SSIs, and many clinicians are not aware of this. Therefore, a systematic review and meta-analysis has been conducted to investigate and quantify this matter. METHODS: Articles were searched in Embase, Medline Ovid, Web of Science, Cochrane Central, and Google Scholar, and data were extracted from relevant studies. Meta-analysis used random effects models to estimate and compare the pooled odds ratios (OR) and corresponding confidence intervals (CIs) of surgery performed during the warmest period of the year and the colder period of the year. RESULTS: The systematic review included 20 studies (58,599,475 patients), of which 14 studies (58,441,420 patients) were included for meta-analysis. Various types of surgical procedures across different geographic regions were included. The warmest period of the year was associated with a statistically significant increase in the risk of SSIs (OR 1.39, 95%CI: [1.34-1.45], P < 0.0001). Selection of specific types of surgical procedures (eg, orthopedic or spinal surgery) significantly altered this increased risk. CONCLUSIONS: The current meta-analysis showed that warm weather seasons are associated with a statistically significant risk increasement of 39% in developing SSIs. This significant risk factor might aid clinicians in preoperative patient information, possible surgical planning adjustment for high risk patients, and potentially specific antibiotic treatments during the warmer weather seasons that could result in decrease of SSIs.

Aspergillus in Critically Ill COVID-19 Patients: A Scoping Review.

Several reports have been published on Aspergillus findings in COVID-19 patients leading to a proposition of new disease entity COVID-19-associated pulmonary aspergillosis. This scoping review is designed at clarifying the concepts on how the findings of Aspergillus spp. in COVID-19 patients were interpreted. We searched Medline to identify the studies on Aspergillus spp. findings in COVID-19 patients. Included were observational studies containing the following information: explicit mention of the total number of the study population, study period, reason for obtaining respiratory samples, case definition, and clinical outcomes. Excluded were case series, case reports and reviews. Identified were 123 publications, and 8 observational studies were included. From the included studies the following issues were identified. The proportion of immunocompromised patients considered as host factors varied from 0 to 17%. Most of the studies did not mention radiographic findings explicitly. Respiratory samples were mostly obtained to investigate clinical deterioration. Aspergillus culture, antigen or PCR testing on bronchoalveolar lavage (BAL) fluid were performed in between 23.3% and 66.3% of the study population. Two studies performed periodic samples of BAL. Galactomannan index (GI) positivity in BAL was between 10% and 28%. GI in blood was found in 0.9% to 6.7% of the available samples. The prevalence of COVID-19-associated pulmonary aspergillosis ranged from 2.7% to 27.7%. Studies compared the mortality between defined cases and non-cases, and all showed increased mortality in cases. No studies showed that antifungal treatment reduced mortality. Concluding, this review showed how studies defined the clinical entity COVID-19-associated pulmonary aspergillosis where positive Aspergillus test in the respiratory sample was the main driver for the diagnosis. There were many differences between studies in terms of test algorithm and Aspergillus test used that largely determined the prevalence. Whether antifungal therapy, either as prophylaxis, pre-emptive or targeted therapy will lead to better outcomes of COVID-19-associated pulmonary aspergillosis patients is still need to be answered.

An outbreak of ST307 extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in a rehabilitation center: An unusual source and route of transmission.

OBJECTIVE: Nosocomial outbreaks due to multidrug-resistant microorganisms in rehabilitation centers have rarely been reported. We report an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBL-K. pneumoniae) on a single ward in a rehabilitation center in Rotterdam, The Netherlands. DESIGN: Outbreak description. SETTING: A 40-bed ward of a rehabilitation center in the Netherlands. METHODS: In October 2016, 2 patients were found to be colonized by genetically indistinguishable ESBL-K. pneumoniae isolates. Therefore, an outbreak management team was installed, by whom a contact tracing plan was made. In addition to general outbreak measures, specific measures were formulated to allow continuation of the rehabilitation process. Also, environmental cultures were taken. Multiple-locus variable-number tandem-repeat analysis and amplification fragment-length polymorphism were used to determine strain relatedness. Selected isolates were subjected to whole-genome multilocus sequence typing. RESULTS: The outbreak lasted 8 weeks. In total, 14 patients were colonized with an ESBL-K. pneumoniae, of whom 11 patients had an isolate belonging to sequence type 307. Overall, 163 environmental cultures were taken. Several sites of a household washing machine were repeatedly found to be contaminated with the outbreak strain. This machine was used to wash lifting slings and patient clothing contaminated with feces. The outbreak was contained after taking the machine temporarily out of service and implementing a reinforced and adapted protocol on the use of this machine. CONCLUSION: We conclude that in this outbreak, the route of transmission of the outbreak strain via the household washing machine played a major role.

Long-term Mortality After Rapid Screening and Decolonization of Staphylococcus Aureus Carriers: Observational Follow-up Study of a Randomized, Placebo-controlled Trial.

OBJECTIVE: To identify patients who benefit most from Staphylococcus aureus screening and decolonization treatment upon admission. BACKGROUND: S. aureus carriers are at increased risk of developing surgical-site infections with S. aureus. Previously, we demonstrated in a randomized, placebo-controlled trial (RCT) that these infections can largely be prevented by detection of carriage and decolonization treatment upon admission. In this study, we analyzed 1- and 3-year mortality rates in both treatment arms of the RCT to identify patient groups that should be targeted when implementing the screen-and-treat strategy. METHODS: Three years after enrolment in the RCT, mortality dates of all surgical patients were checked. One- and 3-year mortality rates were calculated for all patients and for various subgroups. RESULTS: After 3 years, 44 of 431 (10.2%) and 43 of 362 (11.9%) patients had died in the mupirocin/chlorhexidine and placebo groups, respectively. No significant differences in mortality rates were observed between the treatment groups or the subgroups according to type of surgery. In the subgroup of patients with clean procedures (382 cardiothoracic, 167 orthopedic, 61 vascular, and 56 other), mupirocin/chlorhexidine reduced 1-year mortality: 11 of 365 (3.0%) died in the mupirocin/chlorhexidine versus 21 of 301 (7.0%) in the placebo group [hazard ratio = 0.38 (95% CI: 0.18-0.81)]. CONCLUSIONS: Detection and decolonization of S. aureus carriage not only prevents S. aureus surgical-site infections but also reduces 1-year mortality in surgical patients undergoing clean procedures. Such patients with a high risk of developing S. aureus infections should therefore be the primary target when implementing the screen-and-treat strategy in clinical practice.

Reduced costs for Staphylococcus aureus carriers treated prophylactically with mupirocin and chlorhexidine in cardiothoracic and orthopaedic surgery.

BACKGROUND: A multi centre double-blind randomised-controlled trial (M-RCT), carried out in the Netherlands in 2005-2007, showed that hospitalised patients with S. aureus nasal carriage who were treated prophylactically with mupirocin nasal ointment and chlorhexidine gluconate medicated soap (MUP-CHX), had a significantly lower risk of health-care associated S. aureus infections than patients receiving placebo (3.4% vs. 7.7%, RR 0.42, 95% CI 0.23-0.75). The objective of the present study was to determine whether treatment of patients undergoing elective cardiothoracic or orthopaedic surgery with MUP-CHX (screen-and-treat strategy) affected the costs of patient care. METHODS: We compared hospital costs of patients undergoing cardiothoracic or orthopaedic surgery (n=415) in one of the participating centres of the M-RCT. Data from the 'Planning and Control' department were used to calculate total hospital costs of the patients. Total costs were calculated including nursing days, costs of surgery, costs for laboratory and radiological tests, functional assessments and other costs. Costs for personnel, materials and overhead were also included. Mean costs in the two treatment arms were compared using the t-test for equality of means (two-tailed). Subgroup analysis was performed for cardiothoracic and orthopaedic patients. RESULTS: An investigator-blinded analysis revealed that costs of care in the treatment arm (MUP-CHX, n=210) were on average €1911 lower per patient than costs of care in the placebo arm (n=205) (€8602 vs. €10513, p=0.01). Subgroup analysis showed that MUP-CHX treated cardiothoracic patients cost €2841 less (n=280, €9628 vs €12469, p=0.006) and orthopaedic patients €955 less than non-treated patients (n=135, €6097 vs €7052, p=0.05). CONCLUSIONS: In conclusion, in patients undergoing cardiothoracic or orthopaedic surgery, screening for S. aureus nasal carriage and treating carriers with MUP-CHX results in a substantial reduction of hospital costs.

Rapid detection of methicillin-resistant Staphylococcus aureus in screening samples by relative quantification between the mecA gene and the SA442 gene.

Rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) is important to identify patients colonized with this pathogen and implement infection control precautions. We aimed to improve the combined use of the mecA gene polymerase chain reaction (PCR) and the SA442 PCR to detect MRSA in clinical screening samples. In a true MRSA the mecA copy number will be equal to the SA442 copy number, whereas in samples with a methicillin-sensitive Staphylococcus aureus (MSSA) combined with a methicillin-resistant coagulase-negative Staphylococcus (MRCNS) the copy numbers will usually differ. Here we introduce a PCR system, relative quantification PCR (RQ-PCR), which takes this difference into account. RQ-PCR identifies true MRSA in clinical samples with a specificity that is comparable to the SCCmec-based PCRs.

Distinctive patterns in the human antibody response to Staphylococcus aureus bacteremia in carriers and non-carriers.

Staphylococcus aureus is both a prominent cause of nosocomial infections with significant morbidity and mortality and a commensal with nasal carriage in around 30% of the population. The rapid spread of multi-resistant strains necessitates novel therapeutic strategies, a challenging task because the species S. aureus and the host response against it are highly variable. In a prospective study among 2023 surgical and non-surgical patients, 12 patients developed S. aureus bacteremia. They were analysed in detail using a personalized approach. For each patient, the extracellular proteins of the infecting S. aureus strain were identified and the developing antibody response was assessed on 2-D immunoblots. S. aureus carriers showed clear evidence of strain-specific pre-immunization. In all immune-competent bacteremia patients, antibody binding increased strongly, in most cases already at diagnosis. In endogenous infections, the pattern of antibody binding was similar to the pre-infection pattern. In exogenous infections, in contrast, the pre-infection pattern was radically altered with the acquisition of new specificities. These were characteristic for individual patients. Nevertheless, a common signature of 11 conserved S. aureus proteins, recognized in at least half of the bacteremic patients, was identified. All patients mounted a dynamic antibody response to a subset of these proteins.

Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.

BACKGROUND: Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism. Decolonization of nasal and extranasal sites on hospital admission may reduce this risk. METHODS: In a randomized, double-blind, placebo-controlled, multicenter trial, we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection. RESULTS: From October 2005 through June 2007, a total of 6771 patients were screened on admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group (P=0.005). CONCLUSIONS: The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788.)