Comparative analysis of a rapid diagnostic test and scoring tools for ESBL detection in Enterobacterales bloodstream infections for optimizing antimicrobial therapy.

IMPORTANCE: Our study addresses a significant issue in the medical and scientific community-the delayed administration of appropriate antimicrobial treatments due to the time-consuming process of phenotypic susceptibility data collection in gram-negative bloodstream infections. Our research indicates that a multiplex PCR rapid diagnostic test (RDT) significantly outperformed two clinical scoring tools in predicting ceftriaxone susceptibility. Multiplex PCR also led to reduced instances of undertreatment with ceftriaxone and minimized overtreatment with carbapenems. Furthermore, multiplex PCR demonstrated high sensitivity and specificity in predicting ceftriaxone susceptibility. The results of our study underscore the potential RDTs to reduce the time to appropriate antimicrobial therapy, leading to improved patient outcomes and reduced healthcare costs.

Case Report: Leptospirosis Complicated by Persistent, Bilateral Sensorineural Hearing Loss.

The clinical manifestations of leptospirosis range from mild to life-threatening and can impact on multiple organ systems. A wide array of neurological manifestations of leptospirosis have been reported, although the pathophysiology of neuroleptospirosis remains incompletely understood. We present a case of leptospirosis complicated by bilateral sensorineural deafness, with nodular meningitis demonstrated in the internal auditory meatus on magnetic resonance imaging. The patient was treated with doxycycline, ceftriaxone, systemic and topical steroids, and hyperbaric oxygen therapy, with modest, but incomplete, improvement.

Combinational Effect of Selected Medicinal Plants and Antibiotics Against Pathogenic Bacteria.

<b>Background and Objective:</b> The emergence of antibiotic resistance is a primary global health concern. As a result, there is an urgent need for new strategies to combat antibiotic-resistant bacteria. One of these essential strategies is the combination of medicinal plants and antibiotics as an alternative to using antibiotics alone which was the objective of this article. <b>Materials and Methods:</b> Nine plant materials were collected from different Egypt localities and then extracted by water. Water extracts were filtered and added with Mueller-Hinton agar during preparation. Nine test bacteria and 13 standard antibiotics were used in the disc diffusion sensitivity method. <b>Results:</b> The activity of Amikacin was increased when combined with most different plant extracts against <i>Escherichia coli</i> while antagonistic against <i>Pseudomonas aeruginosa</i>. Aztreonam, Ceftriaxone, Gentamicin and Nalidixic acid antibiotics showed antagonistic or indifferent effects when combined with most different plant extracts against <i>E. coli</i>, <i>Klebsiella pneumonia</i> and <i>P. aeruginosa</i>. The synergistic effect was achieved in Aztreonam when combined with all plant extracts, while Nalidixic acid showed antagonistic when combined with most plant extracts against <i>Proteus mirabilis</i>. The antagonistic effect was achieved in Aztreonam, Ceftriaxone and Nalidixic acid when combined with <i>Achillea fragrantissima</i>, <i>Artemisia monosperma</i> and <i>Leptadenia pyrotechnica</i>, also Aztreonam with <i>Lycium shawii</i> extract against <i>Salmonella typhimurium</i>. The <i>A. fragrantissima</i> and <i>A. monosperma</i> increase the activity of Novobiocin and Vancomycin against <i>Bacillus cereus</i> and Ampicillin and Cefazolin against <i>Staphylococcus aureus</i> but Novobiocin activity increased with most plant extracts against <i>S. aureus</i>. <b>Conclusion:</b> The combinations of antibiotics with the extracts of medicinal plants displayed varying degrees of effects, synergistic, antagonistic and indifferent according to antibiotic type, plant extract and test organism.

Tributyrin alleviates gut microbiota dysbiosis to repair intestinal damage in antibiotic-treated mice.

Tributyrin (TB) is a butyric acid precursor and has a key role in anti-inflammatory and intestinal barrier repair effects by slowly releasing butyric acid. However, its roles in gut microbiota disorder caused by antibiotics remain unclear. Herein, we established an intestinal microbiota disorder model using ceftriaxone sodium via gavage to investigate the effects of different TB doses for restoring gut microbiota and intestinal injury. First, we divided C57BL/6 male mice into two groups: control (NC, n = 8) and experimental (ABx, n = 24) groups, receiving gavage with 0.2 mL normal saline and 400 mg/mL ceftriaxone sodium solution for 7 d (twice a day and the intermediate interval was 6 h), respectively. Then, mice in the ABx group were randomly split into three groups: model (M, 0.2 mL normal saline), low TB group (TL, 0.3 g/kg BW), and high TB group (TH, 3 g/kg BW) for 11 d. We found that TB supplementation alleviated antibiotics-induced weight loss, diarrhea, and intestinal tissue damage. The 16S rRNA sequence analysis showed that TB intervention increased the α diversity of intestinal flora, increased potential short-chain fatty acids (SCFAs)-producing bacteria (such as Muribaculaceae and Bifidobacterium), and inhibited the relative abundance of potentially pathogenic bacteria (such as Bacteroidetes and Enterococcus) compared to the M group. TB supplementation reversed the reduction in SCFAs production in antibiotic-treated mice. Additionally, TB downregulated the levels of serum LPS and zonulin, TNF-α, IL-6, IL-1ß and NLRP3 inflammasome-related factors in intestinal tissue and upregulated tight junction proteins (such as ZO-1 and Occludin) and MUC2. Overall, the adjustment ability of low-dose TB to the above indexes was stronger than high-dose TB. In conclusion, TB can restore the dysbiosis of gut microbiota, increase SCFAs, suppress inflammation, and ameliorate antibiotic-induced intestinal damage, indicating that TB might be a potential gut microbiota modulator.

[Prevention of the development of catheter-associated urinary system infections in the early postoperative period].

BACKGROUND: Bladder catheterization is a common medical manipulation that is associated with the risk of complications, including catheter-associated urinary tract infection (CAUTI), which accounts for 80% of all nosocomial infections of the urological profile. AIM: To evaluate the combined use of the biologically active additive Uronext and ceftriaxone in the prevention of the development of CAUTI in the early postoperative period in 120 patients aged 20-80 years with a Foley indwelling catheter. MATERIALS AND METHODS: The patients were divided into 2 groups: in group I (n=60), D-mannose with cranberry extract and vitamin D3 as part of Uronext dietary supplement was administered orally in the form of sachets 48 hours before surgery and after surgery until urethral catheter was placed, as well as intravenous ceftriaxone 1000 mg 2 hours before surgery and in the postoperative period within 7 days. In group II (n=60), ceftriaxone monotherapy was prescribed in a similar way. RESULTS: According to the results of bacteriological examination of the removed urinary catheter on 3-7 days in Uronext group, bacterial growth was absent in 40 patients (66.67%, p<0.05), versus 23 cases (38.33%) in the control group. CONCLUSIONS: The data obtained confirm the efficiency of the use of the biologically active additive Uronext in combination with an antibacterial drug, which allows to recommend this scheme in patients with an indwelling urinary catheter for the prevention of the development of CAUTI.

Cost-minimization analysis of oral versus intravenous antibiotic treatment for Klebsiella pneumoniae liver abscess.

A cost-minimization analysis was conducted for Klebsiella pneumoniae liver abscess (KLA) patients enrolled in a randomized controlled trial which found oral ciprofloxacin to be non-inferior to intravenous (IV) ceftriaxone in terms of clinical outcomes. Healthcare service utilization and cost data were obtained from medical records and estimated from self-reported patient surveys in a non-inferiority trial of oral ciprofloxacin versus IV ceftriaxone administered to 152 hospitalized adults with KLA in Singapore between November 2013 and October 2017. Total costs were evaluated by category and payer, and compared between oral and IV antibiotic groups over the trial period of 12 weeks. Among the subset of 139 patients for whom cost data were collected, average total cost over 12 weeks was $16,378 (95% CI, $14,620-$18,136) for the oral ciprofloxacin group and $20,569 (95% CI, $18,296-$22,842) for the IV ceftriaxone group, largely driven by lower average outpatient costs, as the average number of outpatient visits was halved for the oral ciprofloxacin group. There were no other statistically significant differences, either in inpatient costs or in other informal healthcare costs. Oral ciprofloxacin is less costly than IV ceftriaxone in the treatment of Klebsiella liver abscess, largely driven by reduced outpatient service costs.Trial registration: ClinicalTrials.gov Identifier NCT01723150 (7/11/2012).

Next-generation sequencing in the diagnosis of neurobrucellosis: a case series of eight consecutive patients.

BACKGROUND: Neurobrucellosis (NB) presents a challenge for rapid and specific diagnosis. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has showed power in detection of causative pathogens, even some infrequent and unexpected pathogens. In this study, we presented 8 cases of NB diagnosed by the NGS of CSF. METHODS: Between August 1, 2018 and September 30, 2020, NGS was used to detect causative pathogens in clinically suspected central nervous system (CNS) infections. Data on demographics, clinical features, and laboratory tests, imaging results and NGS results were collected and reviewed. RESULTS: Among the presented 8 patients, Brucella was rapidly detected using NGS of CSF within 1-4 days, despite those eight patients had variable medical history, disease course, clinical manifestations, laboratory tests and imaging findings. NGS showed the sequence reads corresponded to Brucella species were 8 to 448, with genomic coverage of 0.02 to 0.87%. The relative abundance was 0.13% to 82.40% and sequencing depth was 1.06 to 1.24. Consequently, patients were administered with 3 to 6 months of doxycycline, ceftriaxone and rifampicin, double or triple combination, supplemented with symptomatic therapy and were fully recovered except for case 1. CONCLUSION: NGS of CSF provides a powerful tool in detection of Brucella in a prompt and specific manner, and can be considered for first-line diagnostic use in practice.

Ceftriaxone and selenium mitigate seizures and neuronal injury in pentylenetetrazole-kindled rats: Oxidative stress and inflammatory pathway.

Epilepsy is one of the most serious worldwide neurological disorders that lead to the cognitive-psychosocial insults in recurrent seizures. About one third of the patients are drug-resistant, so innovative drugs are needed to manage seizures to improve the quality of life. Ceftriaxone is a cephalosporin antibiotic that increases the expression of glutamate transporters-1 and improves the neurobehavioral effects caused by increased glutamate level in the CNS. Selenium is well known antioxidant. The present study aimed to investigate ceftriaxone and selenium therapeutic effects against epilepsy in rats. Epilepsy was induced by PTZ given at a dose (50 mg/kg I.P) on alternative days for 13 days. Eighty rats were randomly divided into 8 groups: Group1-2; normal and vehicle control, Group 3; PTZ group, Group 4-8; kindled rats received selenium, ceftriaxone100, ceftriaxone200, selenium + ceftriaxone100 and selenium + ceftriaxone200 mg/kg/day respectively for a week. At the end of the study, behavioral tests were performed. Oxidative stress, inflammatory markers, neurotransmitters and GLT-1 were measured in brain tissue homogenate. Brain histopathological investigation was also done. PTZ-kindled rats exhibited increased Racine score, besides behavioral tests and histopathological changes, significant elevation in oxidative stress and inflammatory markers, with decrease in serotonin, dopamine, GABA levels and GLT-1 expressions. Selenium and Ceftriaxone alone or combined treatment decreased Racine score with remarkable improvement in behavioral and histopathological changes. The antioxidant enzymes, neurotransmitters and GLT-1 expressions were increased, along with reduced TNF-α, IL-1 levels. Current study showed that selenium + ceftriaxone100 group represents a possible approach to improve epilepsy particularly through inhibiting oxidative stress and inflammation.

Enhanced adsorption of ceftriaxone antibiotics from water by activated carbon derived from agriculture products waste.

The present work determines efficiency of domestic food waste like tea waste in removing pharmaceutical waste such as ceftriaxone (CEF) from synthetic wastewater. Carbonaceous material; Tea waste activated carbon (TAC) has been employed and it showed high removal capacity of 787.5 mg/g. TAC was characterized using; XPS, XRD, SEM, FT-IR, and BET as well as it approved that the adsorbent a has high surface area of .6 m2 /g. Various experimental parameters are evaluated for the removal efficiency of the synthesized adsorbent under the present study. During the adsorption study through batch experiments, it approved that the adsorption isotherm was fitted to Langmuir, while kinetically fitted to pseudo-second-order; the adsorption process was chemisorption process as the adsorption energy was 23.7 kJ mol-1 . From evaluation thermodynamic parameters the adsorption reaction was endothermic and spontaneous reaction. The different real samples spiked with CEF and studies the efficiency of TAC to remove it. On the other hand, investigated the regeneration efficiency of the TAC and exhibit high regeneration efficiency as it will be used after four cycles with good efficiency of about 84.2%.

Effectiveness of Cefixime for the Treatment of Neisseria gonorrhoeae Infection at 3 Anatomic Sites: A Systematic Review and Meta-Analysis.

BACKGROUND: To treat Neisseria gonorrhoeae infection, the Centers for Disease Control and Prevention recommends a single oral dose of cefixime as an alternative to injectable ceftriaxone. METHODS: We conducted a systematic review and meta-analysis to describe the effectiveness of cefixime in treating N. gonorrhoeae infection at 3 different anatomic sites.We searched PubMed and Embase database to abstract treatment success rates and cefixime dosage/frequency for studies that reported the anatomical site of infection. We included reports published between January 1, 1980, and December 7, 2021. Twenty studies published between 1989 and 2015 were included in our meta-analysis. We calculated pooled treatment success percentages and 95% confidence intervals (CIs) using random-effects models. RESULTS: Of patients who received a 400-mg single dose of cefixime, 824 of 846 (97%; 95% CI, 96%-98%) patients with urogenital infection, 107 of 112 (97%; 95% CI, 84%-100%) patients with rectal infection, and 202 of 242 (89%; 95% CI, 76%-96%) patients with pharyngeal infection were cured. Of patients who received an 800-mg single dose of cefixime, 295 of 301 (98%; 95% CI, 96%-99%) patients with urogenital infection and 21 of 26 (81%; 95% CI, 61%-92%) patients with pharyngeal infection were cured. CONCLUSIONS: Our meta-analysis found that cefixime is highly effective at treating urogenital infections and less effective at treating pharyngeal infections. We recommend more investigation into the effectiveness of cefixime in treating rectal infections and studying multidose therapy for the cefixime treatment of pharyngeal infection.

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.

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.

Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins.

BACKGROUND: Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. OBJECTIVES: To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. MAIN RESULTS: We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low-certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low-certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low-certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low-certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low-certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low-certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of -0.52 days, 95% CI -0.91 to -0.12; 3 trials, 196 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low-certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low-certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low-certainty evidence) and time to defervescence (MD 2.73 days, 95% CI -0.37 to 5.84; 3 trials, 285 participants; very low-certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low-certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Based on very low- to low-certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones.  We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.

Right hip gonococcal septic arthritis treatment with successful transition to oral fluoroquinolone.

We present a case of gonococcal septic arthritis of the right hip diagnosed via synovial fluid cultures. Antimicrobial susceptibility testing of the synovial fluid demonstrated susceptibility to tetracycline, ciprofloxacin, cefixime and ceftriaxone. Our patient was initially treated with ceftriaxone and was successfully de-escalated to oral levofloxacin to complete the treatment. This case is interesting given the rarity of disseminated gonococcal infections in the 21st century and that most clinical isolates of Neisseria gonorrhoeae are increasingly resistant to fluoroquinolones.

Treatment options for neonatal infections in the post-cefotaxime era.

INTRODUCTION: Cefotaxime has been used for the management of neonatal infections since the 1990s for suspected meningitis and to mitigate gentamicin-associated renal injury. Its shortage in 2015 and subsequent removal from the U.S. pharmaceutical market forced providers to consider alternatives. Ceftriaxone, a cephalosporin with an identical antibacterial spectrum of activity to cefotaxime, is contraindicated in neonates due to its risk of biliary pseudolithiasis. Ceftazidime was recommended as an alternative by the American Academy of Pediatrics but is inequivalent. AREAS COVERED: This article addresses indications for cephalosporin use and considerations when selecting an alternative to cefotaxime. Differences among cefotaxime, ceftriaxone, ceftazidime, and cefepime are discussed and compared to the standard-of-care presumptive regimen, ampicillin, and gentamicin. The authors consider the data behind the neonatal contraindication to ceftriaxone and provide recommendations for their application to practice. EXPERT OPINION: The data against ceftriaxone use in neonates remain poor, particularly in the context of the cefotaxime shortage and lack of an equivalent alternative. Ceftriaxone could be considered in low-risk neonates without hyperbilirubinemia or exposure to calcium-containing fluids on a case-by-case basis. Ceftazidime monotherapy for presumptive management of neonatal infections is inappropriate; cefepime should be more frequently utilized in neonates who are poor candidates for ceftriaxone.

Resistance-Guided Therapy for Neisseria gonorrhoeae.

Antimicrobial-resistant Neisseria gonorrhoeae infections are a threat to public health. Novel strategies for combating such resistance include the development of molecular assays to facilitate real-time prediction of antimicrobial susceptibility. Resistance to ciprofloxacin is determined by the presence of a single mutation at codon 91 of the gyrase A gene; molecular assays to guide therapy are commercially available. Resistance to cefixime is conferred via 1 of 6 critical mutations in either the mosaic penA gene or specific loci in the nonmosaic region. Resistance to ceftriaxone is conferred through mutations in 1 of 4 genes: penA, ponA, penB, and mtr; however, the ability to predict reduced susceptibility based on those genes varies by geographic region. Here, we highlight the work done toward the development of 3 such assays for ciprofloxacin, cefixime, and ceftriaxone, discuss the status of our current understanding and ongoing challenges, and suggest future directions.

Randomized controlled trial of the relative efficacy of high-dose intravenous ceftriaxone and oral cefixime combined with doxycycline for the treatment of Chlamydia trachomatis and Neisseria gonorrhoeae co-infection.

OBJECTIVES: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the commonest bacterial causes of sexually transmitted infections in humans with high incidence of co-infection. Treatment with high doses of ceftriaxone (CRO) and cefixime (CFM) is strongly recommended due to the reduced drug susceptibility of NG. However, their safety and efficacy have not been confirmed. We compared the safety and efficacy of a single 1 g intravenous (IV) dose of ceftriaxone (CRO) plus doxycycline (DOX) versus a single 800 mg oral dose of cefixime (CFM) plus DOX for the treatment of NG-CT co-infection. METHODS: An open-label randomized controlled trial was conducted on 125 individuals aged > 18 years with untreated gonorrhea and chlamydia to compare a single 1 g intravenous dose of CRO + DOX and a single 800 mg oral dose of CFM + DOX. The primary outcome was the clearance of NG from all the initially infected sites. Secondary outcomes included symptom resolution, changes in the serum clearance levels, glomerular filtration rate, and antibiotic minimum inhibitory concentrations. RESULTS: Both regimens were highly effective in treating gonorrhea with success rates of 96.7% (95% confidence interval [CI] 88.8-99.1%) for CRO and 95.3% (95% CI 87.1-98.4%) for CFM. However, CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection (odds ratio 4.41, 95% CI 1.11-25.7). The safety profiles of the two regimens were similar. CONCLUSIONS: CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection. CFM + DOX may be indicated in patients with CRO allergy and in settings where CRO is unavailable. Trial registration ClinicalTrials.gov (NCT05216744) on 31/01/22.

Efficacy and safety of Tanreqing injection combined with antibiotics against Streptococcus pneumoniae pneumonia: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Tanreqing injection (TRQ) is a traditional Chinese medicine injection. The goal of this study was to assess the clinical efficacy and safety of TRQ injection in combination with azithromycin or ceftriaxone, as well as azithromycin or ceftriaxone alone, in treating Streptococcus pneumoniae pneumonia (SPP). METHODS: The randomized controlled trial (RCT) of TRQ injection combined with antibiotics versus antibiotics alone in the treatment of SPP was retrieved from Chinese and English databases (the control group was treated with antibiotics alone, while the experimental group received TRQ injection combined with antibiotics). The retrieval period was from the database's inception through February 2022. The data was extracted using the Cochrane Collaboration Network Quality Evaluation Standards, the methodological quality of the included literature was assessed, and the outcome indicators were calculated using RevMan5.4.1 software. RESULTS AND DISCUSSION: A total of 25 RCTs were collected, including 2057 patients. TRQ injection combined with antibiotics significantly improved clinical efficacy and reduced defervescence time, lung rale disappearance time, cough disappearance time, disappearance time of chest pain, and average hospitalization time when compared to control group, according to meta-analysis results (p < 0.05). WHAT IS NEW AND CONCLUSION: In the treatment of SPP, TRQ injection combination with antibiotics can significantly improve the total effect rate when compared to standard western medicine. Due to the low quality of the randomized controlled trials included in this investigation, more high-quality, multi-center, large-sample, prospective, randomized, double-blind clinical studies are needed to confirm the aforementioned conclusions.

Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022.

We describe a gonorrhoea case with ceftriaxone plus high-level azithromycin resistance. In April 2022, an Austrian heterosexual male was diagnosed with gonorrhoea after sexual intercourse with a female sex worker in Cambodia. Recommended treatment with ceftriaxone (1 g) plus azithromycin (1.5 g) possibly failed. Worryingly, this is the second strain in an Asian Neisseria gonorrhoeae genomic sublineage including high-level azithromycin-resistant strains that developed ceftriaxone resistance by acquisition of mosaic penA-60.001. Enhanced resistance surveillance and actions are imperative to prevent spread.