Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

Effectiveness and safety of cefotaxime combined with avibactam for treating multidrug-resistant E coli infections: A systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant Escherichia coli infections are a global health challenge, notably in North America, Europe, Asia, and Africa. This systematic review and meta-analysis evaluates the effectiveness and safety of cefotaxime combined with avibactam, aiming to mitigate these infections' impact and lessen their burden on healthcare systems worldwide. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and PICO frameworks, we conducted a comprehensive literature search across 4 primary databases on May 6, 2023. Studies evaluating the efficacy and safety of cefotaxime and avibactam were included. Key outcomes included treatment success, adverse effects, and microbiological eradication. Quality assessment utilized the Cochrane Collaboration Risk of Bias instrument. Heterogeneity was analyzed using chi-square statistics and the I2 index. Both fixed- and random-effects models were applied as appropriate. Publication bias was rigorously evaluated using Egger linear regression test and funnel plot analysis, ensuring the study's integrity and reliability. RESULTS: The clinical cure rate derived from 8 studies showed no significant difference between the treatment groups (odds ratio [OR] = 1.97, 95% CI: 0.69 to 1.36, P = .86). Analysis of the bacterial clearance rate from the 5 studies also indicated no significant difference (OR = 0.97, 95% CI: 0.42 to 2.25, P = .36). Notably, a reduced mortality rate favoring the experimental group was observed in 6 studies (OR = 0.64, 95% CI: 0.44 to 0.92, P = .012). Comprehensive sensitivity analyses and the assessment of publication bias strengthened the reliability of the results. CONCLUSIONS: Ceftazidime combined with avibactam significantly reduced mortality among patients with multidrug-resistant Escherichia coli infections, indicating its potential as a therapeutic option, especially for carbapenem-resistant Enterobacteriaceae. However, extensive large-scale clinical trials are required to validate these findings.

The effects of switching from ceftriaxone to cefotaxime on the occurrence of third-generation cephalosporin-resistant Enterobacterales: A stepped-wedge cluster randomized trial.

OBJECTIVES: To evaluate the effects of the replacement of ceftriaxone by cefotaxime on the incidence of third-generation cephalosporin-resistant Enterobacterales (3GC-RE). PATIENTS AND METHODS: We conducted a 24-month monocentric prospective, stepped-wedge cluster randomized controlled trial. During the control phase of the study, clinicians prescribed either ceftriaxone or cefotaxime. During the intervention phase, they systematically prescribed cefotaxime. RESULTS: The cefotaxime/ceftriaxone ratio was inversely correlated with the incidence of 3GC-RE. All in all, 3GC-RE incidence was 1.05 (27/25,692) acquired cases/1000 hospitalization days during the control phase and 0.54 (11/20,419) acquired cases/1000 hospitalization days during the intervention phase (incidence rate ratio [IRR] = 0.51 [0.22-1.07], p = 0.06). In multivariable analysis, intervention phase (versus control phase) (p = 0.007), cefotaxime/ceftriaxone ratio (p = 0.003) and imported 3GC-RE (p = 0.005) were associated with the incidence of acquired cases of 3GC-RE. CONCLUSIONS: We found that replacing ceftriaxone with cefotaxime reduced the occurrence of 3GC-RE isolates. More studies are needed to confirm these results.

Antibiotic treatment of neuro-meningeal infections.

In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to beta-lactams. Over recent years, the nationwide pediatric meningitis network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have not recorded any cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (C3G), even though in 2021, strains with a less favorable profile appeared to emerge. These recent data justify renewal of the 2016 recommendations and limitation of vancomycin to the secondary phase of treatment of pneumococcal meningitis when the MIC of the isolated strain against injectable C3Gs is >0.5 mg/L. The only major change proposed by the GPIP in this 2023 update of its recommendations is discontinuation of the recommendation of a combination of ciprofloxacin and cefotaxime in Escherichia coli meningitis in newborns and young infants. The nationwide observatory of meningitis in children is a valuable tool because of its completeness and its continuity over the past 15 years. The maintenance of epidemiological surveillance will allow us to adapt new therapeutic regimens to the evolution of pneumococcal susceptibility profiles and to future serotype-specific changes. Community-acquired cerebral abscesses are rare diseases, of which the management requires a rigorous approach: high-quality imaging, bacteriological sampling prior to antibiotic therapy whenever possible, and antibiotic treatment including metronidazole in addition to cefotaxime. Multidisciplinary collaboration, including infectious disease and neurosurgical advice, is always called for.

Cefotaxime in Enteric Fever: Therapeutic Reappraisal.

Enteric fever is one of the most common infectious diseases in the economically developing world and this bacterial infection is the common most cause of fever in travelers to these endemic areas. Even after the availability and deployment of preventive measures like vaccination against Salmonella typhi (S. typhi) and sanitation practices; effective treatment is paramount to reduce the associated morbidity and mortality. Cephalosporins are antimicrobials belonging to the ß-lactam class with established efficacy, pharmacokinetic, and safety profile by virtue of which, they belong to the group of antibiotics most commonly utilized in clinical practice. They have a broadspectrum of activity against various gram-positive and gram-negative bacteria. Like penicillin, they belong to the ß-lactam class of drugs. Amid such a scenario of rising antimicrobial resistance, a broad-spectrum antibiotic like cefotaxime is a real bliss. Distinctive properties of cefotaxime like broad-spectrum of activity, bactericidal action, stability against the common resistance-causing mechanisms, and good safety profile make it a reliable choice in the therapy landscape of enteric fever. It delivers desired efficacy in such difficult-to-treat scenarios at a manageable tolerability profile. Cefotaxime and ceftriaxone have a comparable spectrum of antimicrobial activity, but both differ in terms of pharmacokinetics. Considering the published literature, cefotaxime seems to be a dependable option for the management of typhoid owing to its effectiveness against S. typhi bundled with an acceptable tolerability profile.

Cefotaxime/sulbactam plus gentamicin as a potential carbapenem- and amikacin-sparing first-line combination for neonatal sepsis in high ESBL prevalence settings.

BACKGROUND: Infection with ESBL-producing Enterobacteriaceae infection is ubiquitous in some neonatal ICUs and increasing levels of antibiotic resistance are a cause for urgent concern. Delineation of bacterial and viral sepsis can be challenging, often leading to patients receiving empirical antibiotics without or whilst waiting for a definitive causal diagnosis. Empirical therapy is often dependent on broad-spectrum 'Watch' antibiotics, contributing to further resistance. METHODS: ESBL-producing Enterobacteriaceae clinical isolates found to have caused neonatal sepsis and meningitis underwent a detailed in vitro screening including susceptibility testing, chequerboard combination analysis and hollow-fibre infection model dynamic analyses using combinations of cefotaxime, ampicillin and gentamicin in combination with ß-lactamase inhibitors. RESULTS: Additivity or synergy was found for all antibiotic combinations against seven Escherichia coli and three Klebsiella pneumoniae clinical isolates. Cefotaxime or ampicillin plus sulbactam combined with gentamicin was able to consistently inhibit the growth of ESBL-producing isolates at typical neonatal doses, and the combination cleared the hollow-fibre infection model system of organisms resistant to each agent alone. The combination of cefotaxime/sulbactam and gentamicin was consistently bactericidal at clinically achievable concentrations (Cmax of 180, 60 and 20 mg/L for cefotaxime, sulbactam and gentamicin, respectively). CONCLUSIONS: The addition of sulbactam to cefotaxime or ampicillin to the typical first-line empirical therapy could obviate the need for carbapenems and amikacin in settings with high ESBL-infection prevalence.

Fucoxanthin Potentiates the Bactericidal Activity of Cefotaxime Against Staphylococcus aureus.

The increasing prevalence of antimicrobial resistance (AMR) in Staphylococcus aureus against commonly used antibiotics is a major global health issue. To prevent the emergence of AMR and maintain the desired therapeutic effect, the use of drug combinations in the therapeutic management of infections can be contemplated. This approach allows for the administration of lower antibiotic dosages without compromising the desired therapeutic outcome. Despite the documented antimicrobial activity of fucoxanthin, a widely recognized marine carotenoid, there are a lack of previous reports exploring its potential to enhance the therapeutic effect of antibiotics. The current study aimed to investigate whether fucoxanthin can inhibit S. aureus including the strains resistant to methicillin and to investigate whether fucoxanthin can enhance the therapeutic effect of cefotaxime, a widely prescribed 3rd-generation cephalosporin ß-lactam antibiotic known to exhibit resistance in certain cases. Synergism or additive interactions were determined using checkerboard dilution and isobologram analysis, while bactericidal activity was carried out using the time-kill kinetic assay. It is important to highlight that a synergistic bactericidal effect was observed in all strains of S. aureus when fucoxanthin was combined with cefotaxime at a specific concentration ratio. These findings suggest that fucoxanthin holds promise in enhancing the therapeutic efficacy of cefotaxime.

High prevalence of ß-lactam and fluoroquinolone resistance in various phylotypes of Escherichia coli isolates from urinary tract infections in Jiroft city, Iran.

BACKGROUND: Urinary tract infection (UTI) is one of the most prevalent infectious diseases with worldwide health threatening. Antimicrobial resistant strains of Escherichia coli (E. coli) are a common cause of UTI which were identified as a treatment challenge. This study aimed to assay the prevalence of common ß-lactam resistance genes including blaTEM, blaSHV, blaCTX-M and blaCMY and phenotypic resistance to commonly used ß-lactam and fluoroquinolone antibiotics in UTIs. These factors were evaluated in various phylogenetic groups (phylotypes) of E. coli isolates. Real-time PCR was applied to detect ß-lactam resistance genes and conventional PCR was used to determine the phylotypes. Phenotypic resistance against ß-lactams (ceftazidime, cefotaxime, aztreonam and ceftriaxone) and fluoroquinolones (ciprofloxacin) were identified by the disc diffusion technique. The ability of extended spectrum ß-lactamases (ESBLs) production in E. coli isolates was detected using the combined disc diffusion method. RESULTS: The prevalence of resistance genes were 89.6% for blaTEM, 44.3% for blaCTX-M, 6.6% for blaSHV and 0.9% for blaCMY. The two high prevalent phylotypes were B2 (29.2%) and D (17.9%) followed by E (14.1%), F (9.4%), C (6.6%) and 10.3% of isolates were unknown in phylotyping. Disc diffusion results showed high prevalence of antibiotic resistance to cefotaxime (88.6%), aztreonam (83%), ceftireaxon (77.3%), ceftazidime (76.4%) and ciprofloxacin (55.6%). Totally, 52.8% of isolates were found as phenotypical ESBL-producers. CONCLUSIONS: This study's results confirmed an explosion of antibiotic resistance amongst E. coli isolates from UTI against ß-lactams and fluoroquinolones. Findings explain the necessity of deep changes in quantity and quality of drug resistance diagnosis and antibiotic therapy strategies. More studies are suggested to better and confident evaluations.

Deep cervical abscesses in children: efficacy of the cefotaxime-rifampicin combination.

The objective is to determine whether a medical treatment, the combination of cefotaxime and rifampicin, is effective in avoiding surgery for managing deep cervical abscesses in children and to determine prognostic factors in the efficacy of this medical treatment. This is a retrospective analysis of all patients under 18 presenting with para- or retro-pharyngeal abscess over the period 2010-2020 in two hospitals' pediatric otorhinolaryngology departments. One hundred six records were included. Multivariate analyses were performed to study the relationship between the prescription of the Cefotaxime-rifampicin protocol at the onset of the management and the use of surgery and to evaluate the prognostic factors of its efficacy. The 53 patients who received the cefotaxime-rifampicin protocol as first-line treatment (vs. 53 patients receiving a different protocol) required surgery less frequently: 7.5% versus 32.1%, validated by a Kaplan-Meier survival curve and a Cox model analysis adjusted for age and abscess size (Hazard Ratio = 0.21). This good outcome of the cefotaxime-rifampicin protocol was not demonstrated when it was instituted as a second-line treatment after the failure of a different protocol. An abscess larger than 32 mm at hospitalization was significantly associated with more frequent use of surgery in multivariate analysis adjusted for age and sex (Hazard Ratio = 8.5).    Conclusions: The cefotaxime-rifampicin protocol appears to be an effective first-line treatment in managing non-complicated deep cervical abscesses in children. What is Known: • Nowadays, medical treatment is preferred for managing deep neck abscesses in children. There has yet to be a consensus on the antibiotic therapy to be proposed. • Staphylococcus aureus and streptococci are the most frequent causative organisms. What is New: • The cefotaxime-rifampicin protocol introduced at first intention is effective, with only 7.5% of patients requiring drainage surgery. • The only risk factor for failure of the medical treatment is the initial size of the abscess.

Antimicrobial resistance profiles of Campylobacter jejuni and Salmonella spp. isolated from enteritis patients in Japan.

Understanding the antimicrobial resistance of Campylobacter jejuni and Salmonella spp. isolated from patients with enteritis will aid in therapeutic decision-making. This study aimed to characterize C. jejuni and Salmonella spp. isolates from patients with enteritis. For C. jejuni, the resistance rates against ampicillin, tetracycline, and ciprofloxacin were 17.2%, 23.8%, and 46.4%, respectively. All the C. jejuni isolates were susceptible to erythromycin, which is recommended as a first-choice antimicrobial if Campylobacter enteritis is strongly suspected. C. jejuni was classified into 64 sequence types (STs), and the five major STs were ST22, ST354, ST21, ST918, and ST50. The ciprofloxacin-resistance rate of ST22 was 85.7%. For Salmonella, the resistance rates against ampicillin, cefotaxime, streptomycin, kanamycin, tetracycline, and nalidixic acid were 14.7%, 2.0%, 57.8%, 10.8%, 16.7%, and 11.8%, respectively. All the Salmonella spp. isolates were susceptible to ciprofloxacin. Therefore, fluoroquinolones are the recommended antimicrobials against Salmonella enteritis. S. Thompson, S. Enteritidis, and S. Schwarzengrund were the three most prevalent serotypes. The two cefotaxime-resistant isolates were serotyped as S. Typhimurium and were found to harbor blaCMY-2. The results of this study would help select antimicrobials for treating patients with Campylobacter and Salmonella enteritis.

Combination of Cefotaxime and Cisplatin Specifically and Selectively Enhances Anticancer Efficacy in Nasopharyngeal Carcinoma.

BACKGROUND: HMOX1 has a dual role in cancers, especially involving chemoresistance. We demonstrate that cephalosporin antibiotics exert strong anticancer activity in nasopharyngeal carcinoma mainly via drastic upregulation of HMOX1. OBJECTIVES: Cephalosporin antibiotics are commonly used for the treatment or prophylaxis of bacterial infectious diseases in cancer patients. It is unknown whether they lead to chemoresistance in cancer patients, especially in nasopharyngeal carcinoma patients, who are being treated or required prophylaxis for an infectious syndrome with cephalosporin antibiotics. METHODS: MTT and clonogenic colony formation assays assessed the viability and proliferation of cultured cancer cells. Flow cytometry was used to detect apoptosis. Tumor growth was assessed using a xenograft model. Microarray and RT-qPCR expression analyses investigated differential gene expression. RESULTS: Cefotaxime enhanced anticancer efficacy of cisplatin in nasopharyngeal carcinoma without enhancing the toxic side effects both in vitro and in vivo. However, cefotaxime significantly reduced the cytotoxicity of cisplatin in other cancer cell lines. Cefotaxime and cisplatin co-regulated 5 differential genes in CNE2 cells in a direction supporting the enhancement of anticancer efficacy, of which, THBS1 and LAPTM5 were further upregulated, STAG1, NCOA5, and PPP3CB were further downregulated. Out of the 18 apoptotic pathways significantly enriched in the combination group, THBS1 and HMOX1 overlapped in 14 and 12 pathways, respectively. Extrinsic apoptotic signaling pathway (GO: 2001236) was the only apoptotic pathway commonly enriched in cefotaxime group, cisplatin group and combination group, and THBS1 and HMOX1 were the overlapped genes of this pathway. THBS1 also overlapped in P53 signaling pathway and ECM-receptor interaction signaling pathway enriched by KEGG. CONCLUSION: Cephalosporin antibiotics are chemosensitizers of conventional chemotherapeutic drugs in the chemotherapy of nasopharyngeal carcinoma, but they may lead to chemoresistance by cytoprotection in other cancers. Cefotaxime and cisplatin co-regulate THBS1, LAPTM5, STAG1, NCOA5 and PPP3CB suggesting their involvement in the enhancement of anticancer efficacy in nasopharyngeal carcinoma. Targeting of P53 signaling pathway and ECM-receptor interaction signaling pathway was correlated to the enhancement. With additional benefit for treatment or prophylaxis of an infectious syndrome, cephalosporin antibiotics can benefit the therapy of nasopharyngeal carcinoma either as anticancer agents or as chemosensitizers of chemotherapeutic drugs in combination chemotherapy.

Response-Guided Therapy With Cefotaxime, Ceftriaxone, or Ciprofloxacin for Spontaneous Bacterial Peritonitis: A Randomized Trial: A Validation Study of 2021 AASLD Practice Guidance for SBP.

INTRODUCTION: For the treatment of spontaneous bacterial peritonitis (SBP), cefotaxime, ceftriaxone, and ciprofloxacin were used as first-line agents. However, considering the increasing rate of antibiotic resistance, it is unclear which of these drugs can be initially recommended. This study aimed to compare the current efficacy of the 3 antibiotics, namely cefotaxime, ceftriaxone, and ciprofloxacin, for the treatment of SBP in patients with cirrhosis with ascites, when guided by therapeutic responses. METHODS: This study was a multicenter, prospective, randomized controlled trial. The inclusion criteria were 16- to 75-year-old patients with liver cirrhosis with ascites, having polymorphonuclear cell count of >250/mm 3 . We performed a follow-up paracentesis at 48 hours to decide continuing or changing the assigned antibiotics and then assessed the resolution rates at 120 and 168 hours of treatment. RESULTS: A total of 261 patients with cirrhosis who developed SBP were enrolled. Most of the patients were diagnosed as those with SBP within 48 hours of admission. The resolution rates at 120 hours, which is the primary endpoint, were 67.8%, 77.0%, and 73.6% in the cefotaxime, ceftriaxone, and ciprofloxacin groups, respectively ( P = 0.388), by intension-to-treat analysis. The 1-month mortality was similar among the groups ( P = 0.770). The model for end-stage liver disease score and the SBP resolution were significant factors for survival. CONCLUSION: The efficacy of empirical antibiotics, such as cefotaxime, ceftriaxone, and ciprofloxacin, against SBP was not significantly different. In addition, these antibiotics administered based on response-guided therapy were still efficacious as initial treatment for SBP, especially in those with community-acquired infections.

Serotype distribution of Streptococcus pneumoniae and pneumococcal vaccine coverage in adults in Turkey between 2015 and 2018.

OBJECTIVE: To evaluate the serotype distribution and antibiotic resistance in pneumococcal infections in adults and to provide a perspective regarding serotype coverage of both current and future pneumococcal vaccines. PATIENTS AND METHODS: This passive surveillance study was conducted with the Streptococcus pneumoniae strains isolated from the specimens of patients with pneumonia (materials isolated from bronchoalveolar lavage), bacteraemia, meningitis, pleuritis and peritonitis between 2015 and 2018. Serogrouping and serotyping were performed by latex particle agglutination and by conventional Quellung reaction using commercial type-specific antisera, respectively. The strains were analysed for penicillin, cefotaxime, erythromycin and moxifloxacin susceptibilities by E-test. RESULTS: In the whole study group (410 samples from adults aged ≥18 years), the most frequent serotypes were 3 (14.1%), 19 F (12%) and 1 (9.3%). The vaccine coverage for PCV13, PCV15, PCV20 and PPV23 was 63.9%, 66.6%, 74.1% and 75.9%, respectively, in all isolates. Penicillin non-susceptibility in invasive pneumococcal disease (IPD) was 70.8% and 57.1% in the patients aged <65 and ≥65 years, respectively. About 21.1% and 4.3% of the patients with and without IPD had cefotaxime resistance. Non-susceptibility to erythromycin and moxifloxacin was 38.2% and 1.2%, respectively. CONCLUSIONS: The results revealed that novel PCV vaccines may provide improved coverage as compared with the currently available vaccine, PCV13. The significant antibiotic resistance rates imply the need to extend the serotype coverage of the vaccines. Continuing the surveillance in pneumococcal diseases is critical to explore the serotype distribution and incidence changes of IPD cases in the population and to inform policy makers to make necessary improvements in the national immunization programmes.Key messagesThis multicentre study demonstrated the most recent serotype distribution and antibiotic resistance in adult population in Turkey.Shifting from PCV13 to novel conjugated vaccines will significantly increase the coverage.Continuing the surveillance in pneumococcal diseases is critical to explore the serotype distribution changes and the incidence of cases with invasive pneumococcal disease in the population.

Invasive pneumococcal infections in France: Changes from 2009 to 2021 in antibiotic resistance and serotype distribution of Streptococcus pneumoniae based on data from the French Regional Pneumococcal Observatories network.

OBJECTIVE: The 23 French Regional Pneumococcal Observatories (ORPs) analyzed antibiotic resistance and serotypes of Streptococcus pneumoniae strains isolated from invasive infections in France over a 12-year period. METHODS: Between 2009 and 2021, the ORPs analyzed 19,319 strains, including 1,965 in children and 17,354 in adults. Strains were assessed for their resistance to penicillin G, amoxicillin and cefotaxime. Serotypes were identified in collaboration with the National Reference Centre. RESULTS: During this period, the number of strains collected yearly decreased significantly. The decrease was particularly pronounced up until 2013, especially in children (-61.0%). However, penicillin non-susceptible strains (PNSPs) increased in children (24.7% in 2009 vs 45.0% in 2021, p < 0.0001) and in adults (27.1% in 2009 vs 31.3% in 2021, p < 0.05), as well as resistance (I + R) to amoxicillin (children: 12.5% in 2009 vs 19.4% in 2021, p < 0.05; adults: 13.4% in 2009 vs 14.5% in 2021, NS) and resistance (I + R) to cefotaxime (children: 8.0% in 2009 vs 13.1% in 2021, p < 0.05; adults: 7.1% in 2009 vs 11.9% in 2021, p < 0.0001). All in all, the proportion of strains belonging to serotypes present in the PCV13 vaccine has fallen sharply, from 64.8% in 2009 to 23.6 % in 2021. At the same time, serotypes such as 8, 10A, 11A, 15B/C and 9N, not included in PCV13, were increasing. CONCLUSION: During the study period, data collected by the network highlighted an increase of invasive PNSPs in children and non-vaccine serotypes. Surveillance of resistance and serotypes remains instrumental, particularly to monitor the evolution of vaccine efficacy.

Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis: Treatment in the Real World and in Guidelines.

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L. We treated 363 episodes of pneumococcal meningitis during the study period. Of these, 24 had no viable strain, leaving 339 episodes with a known MIC for inclusion. Penicillin-susceptible strains accounted for 246 episodes (73%), penicillin-resistant strains for 93 (27%), CTX susceptible for 58, and CTX resistant for 35. Nine patients failed or relapsed and 69 died (20%), of whom 22% were among susceptible cases and 17% were among resistant cases. During the dexamethasone period, mortality was equal (12%) in both susceptible and resistant cases. High-dose CTX (300 mg/Kg/day) helped to treat failed or relapsed cases and protected against failure when used as empirical therapy (P = 0.02), even in CTX-resistant cases. High-dose CTX is a good empirical therapy option for pneumococcal meningitis in the presence of a high prevalence of penicillin and cephalosporin resistance, effectively treating pneumococcal strains with MICs up to 2 mg/L for either penicillin or CTX.

Microbiota Assessment of Pediatric Simple and Complex Acute Appendicitis.

Background and Objectives. The aim of this study is to determine the prevailing microbiota in samples from pediatric patients with acute appendicitis, as well as evaluate the antibacterial sensitivity of the isolated microorganisms, comparing the data obtained with the clinic's antibacterial therapy guidelines. Materials and Methods. The study group consisted of 93 patients between the ages of 7 and 18. All patients underwent a laparoscopic or conventional appendectomy. The children were hospitalized with signs and symptoms suggestive of acute appendicitis. Microbiological cultures from the appendix and abdominal cavity were collected intraoperatively. Results. E. coli was identified in most cases irrespective of the clinical presentation of acute appendicitis. Most strains were susceptible to ampicillin and amoxicillin/clavulanic acid. Five strains of E. coli produced extended spectrum beta-lactamase (ESBL). Pseudomonas aeruginosa (P. aeruginosa) was the second most commonly isolated causative agent. Furthermore, it was common in cases of acute complex appendicitis. Most strains of P. aeruginosa were resistant to amoxicillin/clavulanic acid, ertapenem, ampicillin and cefotaxime, yet were susceptible to ceftazidime. Regardless of the clinical presentation, the samples yielded mixed isolates. Conclusion. E. coli is the main causative agent of acute appendicitis in the pediatric population displaying susceptibility to various antibiotics. P. aeruginosa was more prevalent in cases of acute complex appendicitis. P. aeruginosa isolates were susceptible to ceftazidime; however, they were resistant to cefotaxime, which should, therefore, be removed from guidelines for empirical antibacterial treatment of acute appendicitis due to phenotypic resistance of P. aeruginosa. We recommend antibiotics with distinct implementation to avoid antibiotic resistance.

Synergy of a virulent phage (φAB182) with antibiotics leading to successful elimination of biofilms formed by MDR Acinetobacter baumannii.

Emergence of multiple drug resistant (MDR) strains of Acinetobacter baumannii and a withering drug discovery pipeline necessitates the search for effective alternatives to replace or synergize with currently used antibiotics. In this report, we have described the synergy assessment of a virulent Acinetobacter baumannii phage φAB182 with a wide range of antibiotics. Myophage φAB182 was isolated from sewage against MDR A. baumannii and exhibited maximum stability at 25 °C and pH 7. It also had a short latent period of 9 min with a large burst size of 287. The phylogenetic analysis of its major capsid protein gene indicated an 84.15% similarity to the lytic A. baumannii phage Acj9. In the presence of antibiotics, phage φAB182 showed the highest synergy (p < 0.0001) with colistin, followed by polymixin B, ceftazidime and cefotaxime and this synergistic effect was further validated by time kill kinetics. The combined action of phage φAB182 with colistin, polymixin B, ceftazidime and cefotaxime was also synergistic for the eradication of biofilms formed by A. baumannii as measured by MBECcombination/MBECantibiotic values (<0.25). We thus propose bacteriophage φAB182 as a potential antibacterial candidate in combination therapy. The findings from this study strongly support the use of phage antibiotic synergy for the successful treatment of biofilm forming MDR A. baumannii infections.

Resistance to fosfomycin is increasing and is significantly associated with extended-spectrum ß-lactamase-production in urinary isolates of Escherichia coli.

Fosfomycin has become a therapeutic option in urinary tract infections. Our objective was to evaluate the in vitro activity of fosfomycin against Escherichia coli isolated from urine samples in 2013, 2018 and 2021. We also determined a putative association between fosfomycin resistance and extended-spectrum ß-lactamases (ESBL) production. Fosfomycin activity was evaluated against 7367, 8128 and 5072 Escherichia coli urinary isolates in 2013, 2018 and 2021, respectively. We compare the prevalence of fosfomycin-resistant strains among the ESBL- and non-ESBL-producing isolates. MICs of fosfomycin, cefotaxime, and cefotaxime-clavulanate were determined by a microdilution method. 302 ESBL-producers were selected to determine MICs of fosfomycin by agar dilution and genes encoding ESBLs were detected by PCR. Among the total of ESBL-producing strains, 14.3%, 20.8% and 20% were resistant to fosfomycin in 2013, 2018 and 2021, respectively, whereas fosfomycin resistance in non-ESBL producers was 3.5%, 4.05% and 5.53% for each year (P ≤ 0.001). In the 302 selected ESBL-producing isolates, CTX-M was the main ESBL (228 isolates), being 50.7% CTX-M-15. Resistance to fosfomycin among these ESBL-producing strains was associated (P = 0.049) with isolates that produced the CTX-M type. Our data show that fosfomycin resistance is increasing in Escherichia coli urinary isolates and it is related to ESBL-production. A follow-up of fosfomycin resistance is required.