Evidence for the use of peri- and post-operative antibiotic prophylaxis in autologous breast reconstruction: A systematic review.

BACKGROUND: Autologous breast reconstruction has become standard of care, but there is no consensus on prophylactic antibiotic regimens for this surgical procedure. This review aims to present evidence on the best prophylactic antibiotic protocol to lower the risk of surgical site infections in autologous breast reconstructions. METHODS: The search was performed in PubMed, EMBASE, Web of Science, and Cochrane Library on 25th of January 2022. Data on the number of surgical site infections, breast reconstruction type (pedicled or free flap) and reconstruction timing (immediate or delayed), as well as data on the type, dose, route of administration, timing, and duration of antibiotic treatment were extracted. All included articles were additionally assessed for potential risk of bias by using the revised RTI Item Bank tool. RESULTS: 12 studies were included in this review. No evidence is found that giving post-operative antibiotics for a prolonged period longer than 24 h after surgery is useful in lowering infection rates. This review could not distinguish between the best choice of antimicrobial agent. DISCUSSION: Although this is the first study that collected current evidence on this topic, the quality of evidence is limited due to a small number of available studies (N = 12) with small study populations. The included studies have high heterogeneity, no adjustment for confounding, and interchangeably used definitions. Future research is highly recommended with predefined definitions, and a sufficient number of included patients. CONCLUSION: Antibiotic prophylaxis up to a maximum of 24 h is useful in lowering infection rates in autologous breast reconstructions.

[Carbapenems: take it when needed but leave it if you can]. / Carbapenems: inzetten als het moet, vermijden als het kan.

Surveillance data and literature have shown a worldwide increase in infections with resistant bacteria, which has led to increased prescriptions of carbapenems, which in turn has led to increased carbapenem resistance. There is also an increasing use of carbapenems in the Netherlands, a county usually very conservative in antibiotic use. Carbapenem sparing strategies are essential in an attempt to prevent further rise of infections caused by carbapenem resistant bacteria. This article discusses carbapenem sparing strategies with old forgotten antibiotics and novel antibiotics from a Dutch perspective.

Fosfomycin Vs Ciprofloxacin as Oral Step-Down Treatment for Escherichia coli Febrile Urinary Tract Infections in Women: A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial.

BACKGROUND: We aimed to determine the noninferiority of fosfomycin compared to ciprofloxacin as an oral step-down treatment for Escherichia coli febrile urinary tract infections (fUTIs) in women. METHODS: This was a double-blind, randomized, controlled trial in 15 Dutch hospitals. Adult women who were receiving 2-5 days of empirical intravenous antimicrobials for E. coli fUTI were assigned to step-down treatment with once-daily 3g fosfomycin or twice-daily 0.5g ciprofloxacin for 10 days of total antibiotic treatment. For the primary end point, clinical cure at days 6-10 post-end of treatment (PET), a noninferiority margin of 10% was chosen. The trial was registered on Trialregister.nl (NTR6449). RESULTS: After enrollment of 97 patients between 2017 and 2020, the trial ended prematurely because of the coronavirus disease 2019 pandemic. The primary end point was met in 36 of 48 patients (75.0%) assigned to fosfomycin and 30 of 46 patients (65.2%) assigned to ciprofloxacin (risk difference [RD], 9.6%; 95% confidence interval [CI]: -8.8% to 28.0%). In patients assigned to fosfomycin and ciprofloxacin, microbiological cure at days 6-10 PET occurred in 29 of 37 (78.4%) and 33 of 35 (94.3%; RD, -16.2%; 95% CI: -32.7 to -0.0%). Any gastrointestinal adverse event was reported in 25 of 48 (52.1%) and 14 of 46 (30.4%) patients (RD, 20.8%; 95% CI: 1.6% to 40.0%), respectively. CONCLUSIONS: Fosfomycin is noninferior to ciprofloxacin as oral step-down treatment for fUTI caused by E. coli in women. Fosfomycin use is associated with more gastrointestinal events. CLINICAL TRIAL REGISTRATION: Trial NL6275 (NTR6449).

Oral fosfomycin versus ciprofloxacin in women with E.coli febrile urinary tract infection, a double-blind placebo-controlled randomized controlled non-inferiority trial (FORECAST).

BACKGROUND: Febrile Urinary Tract Infection (FUTI) is frequently treated initially with intravenous antibiotics, followed by oral antibiotics guided by clinical response and bacterial susceptibility patterns. Due to increasing infection rates with multiresistant Enterobacteriaceae, antibiotic options for stepdown treatment decline and patients more frequently require continued intravenous antibiotic treatment for FUTI. Fosfomycin is an antibiotic with high bactericidal activity against Escherichia coli and current resistance rates are low in most countries. Oral Fosfomycin-Trometamol 3000 mg (FT) reaches appropriate antibiotic concentrations in urine and blood and is considered safe. As such, it is a potential alternative for stepdown treatment. METHODS: The FORECAST study (Fosfomycin Randomized controlled trial for E.coli urinary tract infections as Alternative Stepdown Treatment) is a randomized, double-blind, double-dummy, non-inferiority trial in which 240 patients will be randomly allocated to a stepdown treatment with FT or ciprofloxacin (standard of care) for FUTI, caused by Escherichia coli with in vitro susceptibility to both antibiotics. The study population consists of consenting female patients (≥18 years) with community acquired E. coli FUTI. After intravenous antibiotic treatment during at least 48 (but less than 120) hours, and if eligibility criteria for iv-oral switch are met, patients receive either FT (3 g every 24 h) or ciprofloxacin (500 mg every 12 h) for a total antibiotic duration of 10 days. The primary endpoint is clinical cure (resolution of symptoms) 6-10 days post-treatment. Secondary endpoints are microbiological cure 6-10 days post-treatment, clinical cure, mortality, ICU admittance, relapse, reinfection, readmission, additional antibiotic use for UTI, early study discontinuation, adverse events, days of hospitalization and days of absenteeism within 30-35 days post-treatment. The sample size is based on achieving non-inferiority on the primary endpoint, applying a non-inferiority margin of 10%, a two-sided p-value of < 0.05 and a power of 80%. DISCUSSION: The study aims to demonstrate non-inferiority of oral fosfomycin, compared to oral ciprofloxacin, in the stepdown treatment of E. coli FUTI. TRIAL REGISTRATION: Registered at the Nederlands trial register (Dutch trial register) on 4-10-2017. TRIAL REGISTRATION NUMBER: NTR6449 . Secondary ID (national authority): NL60186.041.17.

Quantifying Hospital-Acquired Carriage of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Among Patients in Dutch Hospitals.

BACKGROUND Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are emerging worldwide. Contact precautions are recommended for known ESBL-E carriers to control the spread of ESBL-E within hospitals. OBJECTIVE This study quantified the acquisition of ESBL-E rectal carriage among patients in Dutch hospitals, given the application of contact precautions. METHODS Data were used from 2 cluster-randomized studies on isolation strategies for ESBL-E: (1) the SoM study, performed in 14 Dutch hospitals from 2011 through 2014 and (2) the R-GNOSIS study, for which data were limited to those collected in a Dutch hospital in 2014. Perianal cultures were obtained, either during ward-based prevalence surveys (SoM), or at admission and twice weekly thereafter (R-GNOSIS). In both studies, contact precautions were applied to all known ESBL-E carriers. Estimates for acquisition of ESBL-E were based on the results of admission and discharge cultures from patients hospitalized for more than 2 days (both studies) and a Markov chain Monte Carlo (MCMC) model, applied to all patients hospitalized (R-GNOSIS). RESULTS The absolute risk of acquisition of ESBL-E rectal carriage ranged from 2.4% to 2.9% with an ESBL-E acquisition rate of 2.8 to 3.8 acquisitions per 1,000 patient days. In addition, 28% of acquisitions were attributable to patient-dependent transmission, and the per-admission reproduction number was 0.06. CONCLUSIONS The low ESBL-E acquisition rate in this study demonstrates that it is possible to control the nosocomial transmission of ESBL in a low-endemic, non-ICU setting where Escherichia coli is the most prevalent ESBL-E and standard and contact precautions are applied for known ESBL-E carriers. TRIAL REGISTRATION Nederlands Trialregister, NTR2799, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2799; ISRCTN Registry, ISRCTN57648070, http://www.isrctn.com/ISRCTN57648070 Infect Control Hosp Epidemiol 2018;39:32-39.

Case report on a defective antibody response against pneumococcal serotype 9V in a patient with a single episode of pneumonia.

BACKGROUND: Patients with recurrent respiratory tract infections and an impaired response to pneumococcal polysaccharide vaccination are diagnosed with a specific antibody deficiency. In adult patients with pneumococcal pneumonia an impaired antibody response to the infecting pneumococcal serotype can sometimes be found. It is unknown whether these patients are unable to produce an adequate anti-polysaccharide antibody response to pneumococcal vaccination after recovery. CASE PRESENTATION: The authors describe a case of invasive pneumonia caused by Streptococcus pneumoniae serotype 9V in a previously healthy 35-year-old female. This patient did not produce serotype-specific antibodies against the infecting serotype during disease. After pneumococcal polysaccharide vaccination 3 months after recovery, she responded adequately to most other pneumococcal serotypes, but still had no response to the infecting serotype 9V. However, after 9 years (and prior to pneumococcal-conjugate vaccination) normal antibody levels against 9V were found. These antibody levels further increased after pneumococcal-conjugate vaccination. CONCLUSION: The authors believe that this case is the first description of a temporary deficient response to the infecting pneumococcal serotype in adults, while other reports with similar observations all involved children.

Comparison of a Real-Time Multiplex PCR and Sequetyping Assay for Pneumococcal Serotyping.

BACKGROUND: Pneumococcal serotype identification is essential to monitor pneumococcal vaccine effectiveness and serotype replacement. Serotyping by conventional serological methods are costly, labour-intensive, and require significant technical expertise. We compared two different molecular methods to serotype pneumococci isolated from the nasopharynx of South African infants participating in a birth cohort study, the Drakenstein Child Health Study, in an area with high 13-valent pneumococcal conjugate vaccine (PCV13) coverage. METHODS: A real-time multiplex PCR (rmPCR) assay detecting 21 different serotypes/-groups and a sequetyping assay, based on the sequence of the wzh gene within the pneumococcal capsular locus, were compared. Forty pneumococcal control isolates, with serotypes determined by the Quellung reaction, were tested. In addition, 135 pneumococcal isolates obtained from the nasopharynx of healthy children were tested by both serotyping assays and confirmed by Quellung testing. Discordant results were further investigated by whole genome sequencing of four isolates. RESULTS: Of the 40 control isolates tested, 25 had a serotype covered by the rmPCR assay. These were all correctly serotyped/-grouped. Sequetyping PCR failed in 7/40 (18%) isolates. For the remaining isolates, sequetyping assigned the correct serotype/-group to 29/33 (88%) control isolates. Of the 132/135 (98%) nasopharyngeal pneumococcal isolates that could be typed, 69/132 (52%) and 112/132 (85%) were assigned the correct serotype/-group by rmPCR and sequetyping respectively. The serotypes of 63/132 (48%) isolates were not included in the rmPCR panel. All except three isolates (serotype 25A and 38) were theoretically amplified and differentiated into the correct serotype/-group with some strains giving ambigous results (serotype 13/20, 17F/33C, and 11A/D/1818F). Of the pneumococcal serotypes detected in this study, 69/91 (76%) were not included in the current PCV13. The most frequently identified serotypes were 11A, 13, 15B/15C, 16F and 10A. CONCLUSION: The rmPCR assay performed well for the 21 serotypes/-groups included in the assay. However, in our study setting, a large proportion of serotypes were not detected by rmPCR. The sequetyping assay performed well, but did misassign specific serotypes. It may be useful for regions where vaccine serotypes are less common, however confirmatory testing is advisable.

Detection and serotyping of pneumococci in community acquired pneumonia patients without culture using blood and urine samples.

BACKGROUND: Treatment of community acquired pneumonia (CAP) patients with antibiotics before laboratory-confirmed diagnosis leads to loss of knowledge on the causative bacterial pathogen. Therefore, an increasing number of pneumococcal infections is identified using non-culture based techniques. However, methods for serotyping directly on the clinical specimen remain scarce. Here we present three approaches for detection and serotyping of pneumococci using samples from patients with CAP. METHODS: The first approach is quantitative PCR (qPCR) analysis on blood samples (n = 211) followed by capsular sequence typing (CST) to identify the serotype. The second approach, a urinary antigen assay (n = 223), designated as inhibition multiplex immunoassay (IMIA), is based on Luminex technology targeting 14 serotypes. The third approach is a multiplex immunoassay (MIA) (n = 171) also based on Luminex technology which detects serologic antibody responses against 14 serotypes. The three alternative assays were performed on samples obtained from 309 adult hospitalized CAP patients in 2007-2010 and the results were compared with those obtained from conventional laboratory methods to detect pneumococcal CAP, i.e. blood cultures, sputum cultures and BinaxNOW urinary antigen tests. RESULTS: Using qPCR, MIA and IMIA, we were able to detect the pneumococcus in samples of 56% more patients compared to conventional methods. Furthermore, we were able to assign a serotype to the infecting pneumococcus from samples of 25% of all CAP patients, using any of the three serotyping methods (CST, IMIA and MIA). CONCLUSION: This study indicates the usefulness of additional molecular methods to conventional laboratory methods for the detection of pneumococcal pneumonia. Direct detection and subsequent serotyping on clinical samples will improve the accuracy of pneumococcal surveillance to monitor vaccine effectiveness.

Comparison of real-time PCR and Kato smear microscopy for the detection of hookworm infections in three consecutive faecal samples from schoolchildren in Ghana.

BACKGROUND: The classic technique used to detect hookworm infections in population-based surveys is microscopic examination of Kato thick smears of multiple faecal samples per person as variation in soil-transmitted helminth egg output is common. METHODS: As an alternative to this time-consuming and logistically difficult procedure, a PCR-based method to detect hookworm infections was evaluated. Faecal samples collected from 65 Ghanaian school children during February-June 2006 were examined using both techniques. RESULTS: Thirty-one children with a hookworm infection were detected by Kato examination of three faecal samples compared with 30 children detected by PCR of a single faecal sample and 39 detected by PCR of three faecal samples. CONCLUSION: PCR provides a sensitive alternative to the conventional microscopic detection of hookworm infections.

Invasive pneumococcal disease and 7-valent pneumococcal conjugate vaccine, the Netherlands.

In the Netherlands, the national immunization program includes 7-valent pneumococcal conjugate vaccine (PCV7) for all newborns born after April 1, 2006. We compared the incidence of invasive pneumococcal disease (IPD) and patient and disease characteristics before PCV7 introduction (June 2004-June 2006) with those after PCV7 introduction (June 2008-June 2010). Culture-confirmed IPD cases were identified by 9 sentinel laboratories covering ≈25% of the Dutch population. Significant declines in overall IPD incidence were observed in children <2 (60%) and in persons >65 (13%) years of age. A trend toward gradual increases in non-PCV7 serotype IPD infections was observed in all age groups; the largest increases were among persons 50-64 (37%) and >65 (25%) years of age. In adults, the proportion of immunocompromised persons increased among IPD patients. Overall, deaths from IPD decreased from 16% to 12% because of a lower case-fatality rate for persons with non-PCV7 serotype IPD.

Dexamethasone treatment has no effect on the formation of pneumococcal antibodies during community-acquired pneumonia.

In this study, the effect of dexamethasone on the formation of pneumococcal antibodies during community-acquired pneumonia (CAP) was investigated. No differences between CAP patients receiving dexamethasone as additional therapy and patients receiving a placebo were found with respect to immune response rates and mean baseline and convalescent-phase antibody concentrations.

Longitudinal analysis of pneumococcal antibodies during community-acquired pneumonia reveals a much higher involvement of Streptococcus pneumoniae than estimated by conventional methods alone.

In up to half of all cases of community-acquired pneumonia (CAP), no pathogen can be identified with conventional diagnostic methods. The most common identified causative agent is Streptococcus pneumoniae. In this study, pneumococcal antibody responses during CAP were analyzed to estimate the contribution of the pneumococcus to all cases of CAP for epidemiological purposes. Pneumococcal antibodies against 14 different serotypes were measured in serum of hospitalized CAP patients. Patients participated in one of two consecutive clinical trials in a general 600-bed teaching hospital in the Netherlands (between October 2004 and June 2009). A significant pneumococcal immune response was defined as at least a 2-fold increase in antibody concentrations against a single serotype between an early (day 1) and a late (day 30) serum sample of each patient with an end concentration above 0.35 µg/ml. A total of 349 adult CAP patients participated in two consecutive clinical trials. For 200 patients, sufficient serum samples were available to determine antibody responses: 62 pneumococcal pneumonia patients, 57 nonpneumococcal pneumonia patients, and 81 patients with an unidentified causative agent. A significant immune response was detected in 45% (28/62 patients) of pneumococcal pneumonia patients, in 5% (3/57) of nonpneumococcal pneumonia patients, and in 28% (23/81) of patients with an unidentified causative agent. The estimated contribution of pneumococci in patients with an unidentified causative agent was calculated to be 57% (95% confidence interval, 36 to 86%). A substantial fraction of pneumococcal pneumonia patients do not elicit a serotype-specific immune response.

[Eosinophilia and a solid tumour: ovarian sarcoma]. / Eosinofilie bij een solide tumor: ovariumsarcoom.

A 50-year-old woman developed blood eosinophilia during admission to hospital in connection with abdominal symptoms. Eosinophilia is associated with a broad variety of diseases. The major causes of eosinophilia, i.e. an allergic reaction, a parasitic infection and a haematological malignancy, were ruled out. An ultrasound of the abdomen showed a large tumour in the lower abdomen which, because of the patient's history, was attributed to a uterine myoma. Later, this tumour proved to be a mesenchymal malignancy, and surgery was performed to remove it. Histopathology confirmed a high grade sarcoma which had its origin in the right ovary. It is known that eosinophilia can be a paraneoplastic sign of several carcinomas, but it has only infrequently been described in sarcomas. The pathophysiology of tumour-associated eosinophilia is unknown.