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.

A narrative review of the intermediate category of the antimicrobial susceptibility test: relation with dosing and possible impact on antimicrobial stewardship.

The interpretation of 'susceptible (S)' or 'resistant (R)' results of antimicrobial susceptibility testing is easily understood, but the interpretation of the 'intermediate (I)' category can be confusing. This review critically discusses how this categorization (clinical breakpoints) comes into being with the emphasis on the use of pharmacokinetics and pharmacodynamic data. It discusses the differences between the 'I' according to the CLSI and the EUCAST. This review also discusses the recent EUCAST change of the 'I' definition, and the impact of this change from laboratory and clinical points of view.

Epidemiology of Mycoplasma genitalium and Trichomonas vaginalis in the primary health care setting in the Netherlands.

The aim of this paper is to describe the prevalence of Mycoplasma genitalium and Trichomonas vaginalis in patients who visited general practitioners in the Netherlands. Additionally, we describe the prevalence of M. genitalium resistance to azithromycin and moxifloxacin. We used data from 7,411 consecutive female patients who were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, M. genitalium, and T. vaginalis and data from 5,732 consecutive male patients screened for C. trachomatis, N. gonorrhoeae, and M. genitalium. The prevalence of M. genitalium and T. vaginalis in female patients was 6.7% (95% CI: 6.2 to 7.4) and 1.9% (95%CI: 1.6 to 2.2%), respectively. M. genitalium prevalence in male patients was 3.7% (3.3 to 4.3). M. genitalium co-occurred with C. trachomatis in 1.4% (0.3 to 0.6%) of female and in 0.7% (0.5 to 0.9) of male patients. Macrolide resistance gene mutations and fluoroquinolone resistance gene mutations were detected in 73.8% and 9.9%, respectively. We concluded that M.genitalium is relatively infrequently found in a large general practitioner population in the Netherlands. It can co-occur with C. trachomatis, and is often resistant to azithromycin. Therefore, when treating sexually transmitted infections, these prevalence and resistance data should be taken into account.

Frequency of Positive Aspergillus Tests in COVID-19 Patients in Comparison to Other Patients with Pulmonary Infections Admitted to the Intensive Care Unit.

The aim of this study was to describe the frequency of positive Aspergillus tests in COVID-19 patients and investigate the association between COVID-19 and a positive Aspergillus test result. We compared the proportion of positive Aspergillus tests in COVID-19 patients admitted to the intensive care unit (ICU) for >24 h with two control groups: patients with community-acquired pneumonia with (i) a PCR-confirmed influenza infection (considered a positive control since the link between influenza and invasive aspergillosis has been established) and (ii) Streptococcus pneumoniae pneumonia (in whom positive Aspergillus tests are mostly considered as colonization). During the study period, 92 COVID-19 patients (mean [standard deviation] age, 62 [14] years; 76.1% males), 48 influenza patients (55 [14]; 56.2% males), and 65 pneumococcal pneumonia patients (58 [15], 63,1% males) were identified. Any positive Aspergillus test from any respiratory sample was found in 10.9% of the COVID-19 patients, 6.2% of the patients with pneumococcal pneumonia, and 22.9% of those infected with influenza. A positive culture or PCR or galactomannan test on bronchoalveolar lavage (BAL) fluid only was found in 5.4% of COVID-19 patients, which was lower than in patients with influenza (18.8%) and comparable to that in the pneumococcal pneumonia group (4.6%). Using logistic regression analysis, the odds ratio (OR) (95% confidence interval) for a positive Aspergillus test on BAL fluid for COVID-19 patients was 1.2 (0.3 to 5.1; P = 0.8) compared to the pneumococcal pneumonia group, while it was 0.2 (0.1 to 0.8; P = 0.02) compared to the influenza group. This difference remained significant when corrected for age and sex. In conclusion, in COVID-19 patients, the prevalence of a positive Aspergillus test was comparable to that in patients admitted for pneumococcal pneumonia but substantially lower than what we observed in patients with influenza.

Pre-processing tissue specimens with a tissue homogenizer: clinical and microbiological evaluation.

BACKGROUND: Tissues are valuable specimens in diagnostic microbiology because they are often obtained by invasive methods, and effort should thus be taken to maximize microbiological yield. The objective of this study was to evaluate the added value of using tissue pre-processing (tissue homogenizer instrument gentleMACS Dissociator) in detecting microorganisms responsible for infections. METHODS: We included 104 randomly collected tissue samples, 41 (39.4 %) bones and 63 (60.6 %) soft tissues, many of those (42/104 (40.4 %)) were of periprosthetic origins. We compared the agreement between pre-processing tissues using tissue homogenizer with routine microbiology diagnostic procedure, and we calculated the performance of these methods when clinical infections were used as reference standard. RESULTS: There was no significant difference between the two methods (McNemar test, p = 0.3). Among the positive culture using both methods (n = 62), 61 (98.4 %) showed at least one similar microorganism. Exactly similar microorganisms were found in 42/62 (67.7 %) of the samples. From the included tissues, 55/ 104 (52.9 %) were deemed as infected. We found that the sensitivity of homogenized tissue procedure was lower (83.6 %) than when tissue was processed using tissue homogenizer (89.1 %). Sub-analysis on periprosthetic tissues and soft or bone tissues showed comparable results. CONCLUSIONS: The added value of GentleMACS Dissociator tissue homogenizer is limited in comparison to routine tissue processing.

The accuracy of four commercial broth microdilution tests in the determination of the minimum inhibitory concentration of colistin.

Colistin is considered as one of the last-resort antibiotics and reliable antimicrobial susceptibility testing is therefore crucial. The reference standard for AST according to EUCAST and CLSI is broth microdilution (BMD). However, BMD is labor intensive to perform. Commercial antimicrobial susceptibility tests derived from BMD method are available. We investigated the performance of four different commercial tests: Sensititre™, SensiTest™ Colistin, Micronaut MIC Strip Colistin and UMIC Colistin using 70 clinical isolates (half of them was deemed by VITEK2 as resistant), including isolates from cystic fibrosis patients and mcr-1 bearing isolates. We used two reference standards: BMD and composite MIC as determined by all four tests. Sensititre™ had essential agreement (EA, defined as minimum inhibitory concentration within ± 1 dilution) of 87% and 89% compared to BMD and composite reference standard, respectively. For SensiTest™, the EA's were 93% and 90%. For UMIC, 87% and 90%, and for Micronaut, 83% and 84%. All four tests demonstrated categorical agreement (CA) above 90%. CA for SensiTest™ and Micronaut was both 96%, UMIC 94%, and Sensititre™ 93%. All tests were reproducible as tested in two quality control isolates. In conclusion, in clinical isolates from a large referral center, the four commercial tests for determination of colistin minimum inhibitory concentrations showed acceptable performance.

Is there any difference in quality of prescribing between antibacterials and antifungals? Results from the first global point prevalence study (Global PPS) of antimicrobial consumption and resistance from 53 countries.

Objectives: To compare the quality of antibacterial with antifungal prescribing in the world. Methods: Data from the global point prevalence study (Global PPS) were used. The Global PPS took place on any one day between February and June 2015 in 335 participating hospitals from 53 countries. It collected demographic data on patients treated with antimicrobials and data on prescription characteristics of the antimicrobials. For the present study, the quality of antibiotic prescription was compared with antifungal prescription using logistic regression analysis. The following indicators were compared: the presence of the reason for prescription and stop/review date in notes, and compliance with a local guideline. Results: There were 48565 antimicrobial prescriptions for 34731 patients [median age 63 years (range 0-106); 52.6% male] in the Global PPS. Among these antimicrobials, 43513 (89.6%) were antibacterials and 2062 were antifungals for systematic use, and these data were used in this study. Reasons for prescriptions [77.7% versus 71.8%, OR 1.4 (95% CI 1.2-1.5)] and stop/review dates [38.3% versus 31.9%, OR 1.3 (1.2-1.5)] were found more often in notes for antibacterials than for antifungals. Antibacterials were prescribed less often according to local guidelines than antifungals [57.0% versus 71.0%, OR 0.6 (0.5-0.6)]. Conclusions: There are differences in the quality of antibacterial and antifungal prescribing and we identified opportunities that can be used to improve the quality of antimicrobial prescribing.

A Multidisciplinary Infection Control Bundle to Reduce the Number of Spinal Cord Stimulator Infections.

OBJECTIVE: To investigate the effect of a quality improvement project that resulted in an infection control bundle to reduce the number of spinal cord stimulator (SCS) infections. MATERIALS AND METHODS: The study was performed in a single center for neuromodulation from January 1, 2014, through May 31, 2016. In response to a high number of surgical site infections (SSIs) after SCS surgery, a multidisciplinary team analyzed the surgical process and developed an infection prevention bundle consisting of five items: 1) showering and decolonization for five days prior to surgery and showering in the hospital on the morning of surgery; 2) performing the SCS implantation as the first in the daily operating room (OR) program; 3) maintaining a minimal number of people in the OR; 4) providing home care nurses with a folder with SCS wound care instructions including pictures; 5) giving oral specific wound care instructions to patients. The number of infections was calculated for the baseline, implementation, and sustainability phases. RESULTS: A total of 410 SCS surgeries were performed during the study period. In the preintervention phase, 26/249 (10.4%) SCS surgeries were infected. During the implementation and sustainability phase, 2/59 (3.4%) and 1/102 (1.0%) SCS surgeries were infected, respectively. The reduction in the number of infections in pre and postintervention phase was statistically significant (p = 0.003). CONCLUSION: Multidisciplinary measures to reduce SSIs reduced the number of SCS associated infections in our study setting.

Polymicrobial vertebral osteomyelitis after oesophageal biopsy: a case report.

BACKGROUND: While most cases of polymicrobial vertebral osteomyelitis are secondary to hematogenous seeding, direct inoculation during spinal surgery and contiguous spread from adjacent soft tissue are also potential routes whereby pathogens may infect the spine. CASE PRESENTATION: A 74 year-old man presented with an exacerbation of back pain after a fall. His past medical history included hepatocellular and oesophageal carcinoma. Three months earlier he had undergone an endoscopic biopsy of the oesophagus for routine follow-up of his oesophagus carcinoma. He also underwent a vertebroplasty due to suspected pathologic fracture. On admission to hospital, magnetic resonance imaging revealed an infiltrative process at the level of the 5th and 6th thoracic vertebrae. Blood cultures were positive for both Streptococcus mitis and Gemella morbillorum. During his course of antibiotic therapy he developed an abscess at the level of 8th thoracic vertebrae and culture of this abscess grew Candida albicans. He was treated with antibiotics and antifungal drugs and recovered fully. CONCLUSION: Vertebral osteomyelitis may be caused by direct spread following an oesophageal procedure. Microbiological diagnosis is essential to target the specific pathogen, especially in cases of polymicrobial infection.

Case series of patients with Fusobacterium nucleatum bacteremia with emphasis on the presence of cancer.

Fusobacterium nucleatum is anaerobic oral microbiota that might be associated with cancer. We reported 22 consecutive cases of patients (mean age of 63.8 years (range 34-89), 59.1% male) with F. nucleatum bacteremia that were admitted to a university hospital over a 10-year period. In 17 (77.2%) of these patients, F. nucleatum was the sole possible pathogen. Seven of the 22 patients (31.8%) had active cancer: esophagus carcinoma (n = 3), hematologic malignancies (n = 1), gastrointestinal stromal tumor (n = 1), melanoma (n = 1), and breast cancer (n = 1). In six out of seven patients (85.7%), the F. nucleatum was found within six months of the diagnosis of cancer. Four of seven (57.1%), patients with cancer were on chemotherapy. Three of 22 patients (13.4%) died within 1 month of F. nucleatum bacteremia due to cancer. In conclusion, F. nucleatum bacteremia occurs rarely and when it is found, it is often in patients with cancer, especially those with a recent diagnosis.

Fusobacterium necrophorum and other Fusobacterium spp. isolated from head and neck infections: A 10-year epidemiology study in an academic hospital.

BACKGROUND: Fusobacterium spp. from clinical specimens are increasingly reported. We sought to describe the epidemiology, the microbiological, and the clinical characteristics of head and neck infections caused by Fusobacterium necrophorum and other Fusobacterium spp. MATERIALS AND METHODS: Retrospective cohort study between October 1st, 2004 and September 30(th), 2014 performed in an academic hospital. Electronic patient charts and the laboratory information system were reviewed for demographic and microbiological data. The number and percentages of specific diagnosis and treatment among patients with positive Fusobacterium spp. culture were calculated. The incidence was calculated based on the number of specimens investigated each year. RESULTS: Included were 230 cultures of 230 patients (median age of 28 years, 61.7% men). F. necrophorum was often found in young patients with high C-reactive protein (CRP) and high number of leukocytes in blood. Other Fusobacterium spp. were often found in middle aged patients with relatively high CRP and slightly increased leukocytes. Three major causes of the isolation of F. necrophorum and other Fusobacterium spp. were acute tonsillitis (n = 18, incidence of 0.2%), peritonsillar abscess (n = 39, 0.5%) and acute otitis (n = 45, 0.1%). While F. necrophorum was found in majority (37/57) of patients with acute tonsillitis or peritonsillar abscess, Fusobacterium spp. other than F. necrophorum were found in the majority (35/45) of patients with acute otitis. Isolated fusobacteria were susceptible to beta-lactam antibiotics, clindamycin and metronidazole. The outcomes of patients with Fusobacterium spp. were good. CONCLUSION: F. necrophorum and other Fusobacterium spp. are rare cause of head and neck infections. The infections are well treated by combination of antibiotics and surgery.

A descriptive study on the surgery and the microbiology of Gustilo type III fractures in an university hospital in Switzerland.

OBJECTIVE: To describe the epidemiology, the surgical treatment, the microbiology, the antibiotic prophylaxis and the outcome of patients with the most severe type of open fractures. METHODS: Retrospective chart reviews of patients with Gustilo type III open fracture admitted to an university hospital in Switzerland between January 2007 and December 2011. The patient's and fracture's characteristics, surgery, antibiotic prophylaxis, and microbiology findings at the initial and at the revision surgery were described. RESULTS: Thirty patients were included (83% male, mean age 41 years). More than half of the patients had polytrauma. In all patients, debridement and stabilization surgery (70% using external fixation) were performed at admission. Soft tissue reconstruction was performed in 87% and in 23% immediate bone graft was performed. Antibiotic prophylaxis were given in all patients for a median duration of 9 days (60% received amoxicillin/clavulanic acid). Positive bacterial culture was found in 53% of the patients at initial surgery and in 88% at revision surgery. At initial and revision surgery, 47% and 88% of the pathogens were amoxicillin/clavulanic acid-resistant. Treatment outcome was favorable in 24 of 30 patients (80%) and in six cases (20%) an amputation had to be performed. None of the patients had chronic bone infection. CONCLUSIONS: Positive cultures were found often in open fractures. Amoxicillin/clavulanic acid which is often mentioned in many guidelines as prophylaxis in open fractures does not cover the most common isolated organisms. The combination of surgery and antibiotic prophylaxis leads to good outcome in Gustilo type III fracture.

Evaluation of a chromogenic biplate medium (ChromID MRSA/ChromID S. aureus) for the simultaneous detection of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in preoperative screening samples from the anterior nares.

We evaluated the performance of the ChromID MRSA/ChromID S. aureus biplate for the simultaneous detection of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in preoperative screening samples. The sensitivity and specificity were 94.2% and 93.6%, respectively, for the S. aureus compartment and 92.9% and 99.7% for the MRSA compartment after 48 h incubation.

How to verify and validate a Clinical Microbiology test before it can be used in routine diagnostics, a practical guide.

BACKGROUND: Before a new test can be routinely used in your laboratory, its reliability must be established in the laboratory where it will be used. International standards demand validation and verification procedures for new tests. The International Organization for Standardization (ISO) 15189 was recently updated, and the European Commission's In Vitro Diagnostic Regulation (IVDR) came into effect. These events will likely increase the need for validation and verification procedures. OBJECTIVES: This paper aims to provide practical guidance in validating or verifying microbiology tests, including antimicrobial susceptibility tests in a clinical microbiology laboratory. SOURCES: It summarizes and interprets standards, such as ISO 15189: 20222 and regulations, such as IVDR 2017/745. CONTENT: The reasons for choosing a new test and the outline of the validation and verification plan are discussed. Further, the following topics are touched upon: the choice of reference standard, number of samples, testing procedures, how to solve the discrepancies between results from new test and reference standard, and acceptance criteria. Arguments for selecting certain parameters (such as reference standard and samples size) and examples are given. IMPLICATIONS: With the expected increase in validation and verification procedures due to implementation of IVDR, this paper may aid in planning and executing these procedures.

Clinical outcomes of rifampicin combination therapy in implant-associated infections due to staphylococci and streptococci: A systematic review and meta-analysis.

OBJECTIVES: Adjunctive rifampicin for implant-associated infections is controversial. This study investigated the clinical outcomes of rifampicin combination therapy compared with monotherapy in treating prosthetic joint infection (PJI) or prosthetic valve endocarditis (PVE) due to staphylococci and streptococci. METHODS: A systematic search was performed from inception to 13 June 2022 in Embase, MEDLINE, Cochrane and Web of Science to investigate the clinical outcomes of rifampicin combination therapy compared with monotherapy in treating staphylococcal and streptococcal PJI or PVE. Randomised controlled trials (RCTs) and observational studies were included in the systematic review and meta-analysis. RESULTS: Fourteen studies were included. A moderate quality of evidence was found in favour of rifampicin in patients with staphylococcal PJI who underwent a debridement, antibiotics and implant retention (DAIR) procedure [odds ratio = 2.49, 95% confidence interval (CI) 1.93-3.23]. Including the two RCTs only, adding rifampicin to the antibiotic regimen after DAIR was also in favour of rifampicin, but this was not statistically significant (risk ratio = 1.27, 95% CI 0.79-2.04; n = 126). Pooling data for patients with staphylococcal PJI who underwent a two-stage procedure showed that adding rifampicin was not associated with therapeutic success. Limited evidence was found for the use of rifampicin for PVE caused by staphylococci. CONCLUSIONS: Adding rifampicin in the treatment of staphylococcal PJI treated by DAIR clearly increased the likelihood for therapeutic success. The clinical benefit of adjunctive rifampicin in the treatment of other staphylococci and streptococci implant-associated infections is still unclear.

Evaluating the Clinical Relevance of Routine Sonication for Periprosthetic Hip or Knee Joint Infection Diagnosis.

Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty. PJI screening and conventional cultures may be inconclusive. Sonication fluid culturing stands out as a valuable adjunct technique for PJI diagnosis. This study aims to determine the clinical relevance of routine sonication for all (a)septic revisions. All patients who underwent (partial) hip or knee revision arthroplasty between 2012 and 2021 were retrospectively reviewed. We formed three groups based on the European Bone and Joint Society PJI criteria: infection confirmed, likely, and unlikely. We analyzed clinical, laboratory, and radiological screening. Sensitivity and specificity were calculated for synovial fluid (preoperative), tissue, and sonication fluid cultures. We determined the clinical relevance of sonication as the percentage of patients for whom sonication confirmed PJI; 429 patients who underwent (partial) revision of hip or knee arthroplasty were included. Sensitivity and specificity were 69% and 99% for synovial fluid cultures, 76% and 92% for tissue cultures, and 80% and 89% for sonication fluid cultures, respectively. Sonication fluid cultures improved tissue culture sensitivity and specificity to 83% and 99%, respectively. In 11% of PJIs, sonication fluid cultures were decisive for diagnosis. This is applicable to acute and chronic infections. Sonication fluid cultures enhanced the sensitivity and specificity of PJI diagnostics. In 11% of PJI cases, causative pathogens were confirmed by sonication fluid culture results. Sonication fluid culture should be performed in all revision arthroplasties.

High bacterial load in negative pressure wound therapy (NPWT) foams used in the treatment of chronic wounds.

No earlier study has investigated the microbiology of negative pressure wound therapy (NPWT) foam using a standardized manner. The purpose of this study is to investigate the bacterial load and microbiological dynamics in NPWT foam removed from chronic wounds (>3 months). To determine the bacterial load, a standardized size of the removed NPWT foam was sonicated. The resulting sonication fluid was cultured, and the colony-forming units (CFU) of each species were enumerated. Sixty-eight foams from 17 patients (mean age 63 years, 71% males) were investigated. In 65 (97%) foams, ≥ 1 and in 37 (54%) ≥ 2 bacterial types were found. The bacterial load remained high during NPWT treatment, ranging from 10(4) to 10(6) CFU/ml. In three patients (27%), additional type of bacteria was found in subsequent foam cultures. The mean bacterial count ± standard deviation was higher in polyvinyl alcohol foam (6.1 ± 0.5 CFU/ml) than in polyurethane (5.5 ± 0.8 CFU/ml) (p = 0.02). The mean of log of sum of CFU/ml in foam from 125 mmHg (5.5 ± 0.8) was lower than in foam from 100 mmHg pressure (5.9 ± 0.5) (p = 0.01). Concluding, bacterial load remains high in NPWT foam, and routine changing does not reduce the load.

Valid Evidence for Diagnosis and Treatment of Infections in the Intensive Care Unit: Beyond Randomized Control Trial Study Design (Trial Emulation and Machine Learning).

Infection in critically ill patients is an important problem [...].