Alterations in gut microbiota and inflammatory cytokines after administration of antibiotics in mice.

Antibiotics are widely used to treat bacterial infection and reduce the mortality rate, while antibiotic overuse can cause gut microbiota dysbiosis. The impact of antibiotics on gut microbiota is not fully understood. In our study, four commonly used antibiotics (ceftazidime, cefoperazone-sulbactam, imipenem-cilastatin, and moxifloxacin) were given subcutaneously to mice, and their impacts on the gut microbiota composition and serum cytokine levels were evaluated through 16S rRNA analysis and a multiplex immunoassay. Antibiotic treatment markedly reduced gut microbiota diversity and changed gut microbiota composition. Antibiotic treatment significantly increased and decreased the abundance of Firmicutes and Bacteroidota, respectively. The antibiotic treatments increased the abundance of opportunistic pathogens such as Enterococcus and decreased that of Lachnospiraceae and Muribaculaceae. For moxifloxacin, the significantly high abundance of Enterococcus and Klebsiella was observed after 14 and 21 days of treatment. However, a relatively low abundance of opportunistic pathogens was found after 14 days of imipenem-cilastatin treatment. Additionally, the serum levels of various pro-inflammatory cytokines, such as IL-1ß, IL-12 (p70), and IL-17, significantly increased after 21 days of antibiotic treatments. Overall, these results provide a guide for rational use of antibiotics in clinical settings: short-term use of moxifloxacin is recommended with regard to gut microbiota health, and the 14-day use of imipenem-cilastatin may have a less severe impact than other antibiotics.IMPORTANCEAntibiotic treatments are directly associated with changes in gut microbiota and are effective against both pathogens and beneficial bacteria. Gut microbiota dysbiosis induced by antibiotic treatment could increase the risk of some diseases. Therefore, an adequate understanding of gut microbiota changes after antibiotic use is crucial. In this study, we investigated the effects of continuous treatment with antibiotics on gut microbiota, serum cytokines, and intestinal inflammatory response. Our results suggest that short-term use of moxifloxacin is recommended, and the 14-day use of imipenem-cilastatin may have a less severe effect on gut microbiota health than cefoperazone-sulbactam. These results provide useful guidance on the rational use of antibiotics with regard to gut microbiota health.

In Vitro Activity of Various Sulbactam Compounds and Piperacillin/Tazobactam against Clinical Isolates of Different Gram-Negative Bacteria.

To provide direction for clinical application and pharmaceutical exploitation, the in vitro activity of sulbactam compounds and PIP/TAZ 8 : 1 against clinical isolates of Gram-negative bacteria (GNB, n = 976) was evaluated according to Clinical and Laboratory Standards Institute (CLSI) 2019. By minimal inhibitory concentrations (MICs), the resistance rate of all GNB to AMP/SBT 2 : 1 (56.9-100%) was significantly higher than other drugs, except the resistance rate of Acinetobacter baumannii (Aba, n = 204) to piperacillin/tazobactam (PIP/TAZ 8 : 1, 78.4%) which was close to it (76.5%). Additionally, the resistance rate of Aba to other compounds except AMP/SBT 2 : 1 differed greatly, but that of Klebsiella pneumonia (Kpn, n = 205) varied rarely. In addition, Escherichia coli (Eco, n = 204) and Kpn demonstrated low and high resistance rates, respectively. Compared with cefoperazone/sulbactam (CPZ/SBT 2 : 1), PIP/TAZ 8 : 1 had advantage in anti-Eco (RR = 0.5and OR = 2.17) and anti-Kpn activity (RR = 0.88and OR = 1.27), while its activity against Pseudomonas aeruginosa (Pae: n = 194, RR = 0.91, and OR = 1.12), Aba (RR = 1.31 and OR = 0.41), and other Enterobacteriaceae (other Ebc: n = 169, RR = 1.40, and OR = 0.62) was not better than CPZ/SBT 2 : 1. Although it had advantage against Eco (RR = 0.60 and OR = 1.78), Pae (RR = 0.67 and OR = 1.63), and Aba (RR = 0.70 and OR = 2.05), the inhibition effect of piperacillin/sulbactam (PIP/SBT 2 : 1) against Kpn (RR = 0.94 and OR = 1.12) and other Ebc was just similar with CPZ/SBT 2 : 1 (RR = 0.93 and OR = 1.10). Furthermore, the anti-Eco (RR = 0.70 and OR = 1.50), anti-Kpn (RR = 0.89 and OR = 1.24), and anti-Pae (RR = 0.74 and OR = 1.46) activities of ceftazidime/sulbactam (CAZ/SBT 1 : 1) had a weak advantage, while its activity against Aba (RR = 0.94 and OR = 1.15) and other Ebc (RR = 0.79 and OR = 1.36) was just close to CPZ/SBT 2 : 1. Moreover, the inhibitory effect of PIP/SBT 1 : 1 against all tested clinical species was more active than CPZ/SBT 2 : 1, while that of CAZ/SBT 2 : 1 against all species of bacteria analyzed was weaker than the controls.

Antibiotic perturbation of the murine gut microbiome introduces inter-individual susceptibility to arsenic.

Arsenic is a Group 1 human carcinogen and at least 200 million people around the world are exposed to unsafe levels of arsenic, predominantly through contaminated drinking water. Arsenic has also been used for hundreds, if not thousands, of years as an intentional poison due to its odorless/tasteless properties and the general lack of technology required to identify it. Both acute and chronic arsenic-related health outcomes are highly variable among similarly exposed individuals even after controlling for important factors, like host genetics, making the mechanisms underlying this often-made epidemiologic observation difficult to experimentally address and not fully understood. Here, we describe an experimental model of arsenic exposure in C57BL/6 mice that recapitulates key aspects of inter-individuality in disease observed in humans. We show that co-administration of the antibiotic, cefoperazone, and high-level arsenic (100 ppm, inorganic sodium arsenate) results in incomplete mortality with a ratio of 60 % lethality to 40 % survival, and that survival, at least in part, depends not only on an intact microbiome but also a regulated response involved with water transport. This work provides an experimental framework for identifying critical pathways involved in generating inter-individual variability in disease outcome following arsenic exposure.

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93: A CARE case report.

RATIONALE: Steroid-resistant nephrotic syndrome (SRNS) is a special kidney disease. SRNS is characterized by steroid-resistant, clinical variability, and genetic heterogeneity. Patients with SRNS often may eventually need renal transplantation. PATIENT CONCERNS: A 10-month-old Chinese male infant presented with oliguria, renal dysfunction, hypertension, and anemia. DIAGNOSES: Combined with clinical manifestations, laboratory testing and sequencing results, the patient was diagnosed as SRNS. INTERVENTIONS: Combined intravenous methylprednisolone and cefoperazone sulbactam did not improve the patient's condition. Thus, SRNS associated with hereditary nephrotic syndrome was strongly suspected. Genetic testing for hereditary renal disease of the patient revealed 2 novel heterozygous mutations in the Nucleoporin 93 (NUP93) gene, which were predicted pathogenic and harmful by bioinformatic softwares of SIFT, PolyPhen_2 and REVEL. OUTCOMES: As general physical health deterioration and renal dysfunction, the patient died of a severe infection. LESSONS: The novel NUP93 heterozygous mutations identified in the current study broadened the genetic spectrum of SRNS and further deepened our insight into pathogenic mutations of NUP93 to improve disease diagnosis.

Glyphosate poisoning - a case report.

Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and the surfactant polyoxyethylene amine (POEA)- mediated cardiotoxicity. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. There is no antidote and aggressive supportive therapy is the mainstay of treatment for glyphosate poisoning. We present a 69-year-old female patient with suicidal consumption of around 500 ml of Glycel®. Initially, gastric lavage was done and intravenous fluids were given. Within two hours of presentation, the patient developed respiratory distress needing intubation, hypotension needing vasopressor support, and severe lactic acidosis. She also developed acute respiratory distress syndrome, hypokalemia, hypernatremia, and aspiration pneumonia. Our patient was critically ill with multiple poor prognostic factors, but with timely aggressive supportive management, the patient gradually recovered.

Metagenomic Alterations in Gut Microbiota Precede and Predict Onset of Colitis in the IL10 Gene-Deficient Murine Model.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are chronic inflammatory disorders where predictive biomarkers for the disease development and clinical course are sorely needed for development of prevention and early intervention strategies that can be implemented to improve clinical outcomes. Since gut microbiome alterations can reflect and/or contribute to impending host health changes, we examined whether gut microbiota metagenomic profiles would provide more robust measures for predicting disease outcomes in colitis-prone hosts. METHODS: Using the interleukin (IL) 10 gene-deficient (IL10 KO) murine model where early life dysbiosis from antibiotic (cefoperozone [CPZ]) treated dams vertically transferred to pups increases risk for colitis later in life, we investigated temporal metagenomic profiles in the gut microbiota of post-weaning offspring and determined their relationship to eventual clinical outcomes. RESULTS: Compared to controls, offspring acquiring maternal CPZ-induced dysbiosis exhibited a restructuring of intestinal microbial membership in both bacteriome and mycobiome that was associated with alterations in specific functional subsystems. Furthermore, among IL10 KO offspring from CPZ-treated dams, several functional subsystems, particularly nitrogen metabolism, diverged between mice that developed spontaneous colitis (CPZ-colitis) versus those that did not (CPZ-no-colitis) at a time point prior to eventual clinical outcome. CONCLUSIONS: Our findings provide support that functional metagenomic profiling of gut microbes has potential and promise meriting further study for development of tools to assess risk and manage human IBD.

Campylobacter upsaliensis isolated from a giant hepatic cyst.

Campylobacter upsaliensis is an enteropathogenic bacterium in animals, and is also rarely isolated from humans, where it can cause enteritis and bacteremia. This report describes the first case of isolation of C. upsaliensis from an infected giant hepatic cyst. This bacterium could not be cultured from abscess punctuate in a usual Campylobacter-selection medium (charcoal cefoperazone deoxycholate agar medium), because of high concentration of cefoperazone as a selection agent. It could not identified by matrix-assisted laser desorption ionization-time of flight mass spectrum. Rather, it was identified as C. upsaliensis by whole genome sequencing, including by multilocus sequence typing.

Effectiveness of Cefoperazone-sulbactam alone and Combined with Tigecycline in the Treatment of Multi-drug Resistant Acinetobacter Baumannii Pulmonary Infection.

The aim of this study was to compare the effectiveness of cefoperazone-sulbactam alone and combined with tigecycline in the treatment of multi-drug resistant acinetobacter baumannii pulmonary infection. It was an experimental study carried out from April 2016 to September 2018. One hundred and fourteen patients with multi-drug resistant acinetobacter baumannii pulmonary infection were randomly divided into group A and group B with 57 cases in each group. Group A was treated with cefoperazone-sulbactam sodium alone, and group B was treated with cefoperazone-sulbactam combined with tigecycline. After 14 days of treatment, serum levels of PCT, CRP, TNF-a and IL-6 in group B were lower than those in group A (all p <0.001); APACHE II scores of group B were lower than those of group A (p <0.001). Compared with cefoperazone-sulbactam sodium alone, cefoperazone-sulbactam combined with tigecycline can effectively reduce the inflammatory response of patients with multi-drug resistant acinetobacter baumannii pulmonary infection; and thus a better prognosis can be obtained.

The effect of cefoperazone sulbactam and piperacillin tazobactam on mortality in Gram-negative nosocomial infections.

Cefoperazone-sulbactam (CS) and piperacillin-tazobactam (TZP) are used in the treatment of Gram-negative nosocomial infections (NIs). We aimed to compare the effects of these two antibiotics on mortality and treatment success. Patients treated with CS or TZP empirically for at least three days with suspicion of NI were included in this retrospective study. In total, 308 (154 patients in both treatment arms) patients were analyzed. Treatment success rate in CS and TZP group respectively (50% vs 51.2%, p = 0.18), 28-day mortality rate (46.1% vs 42.8%, p = 0.56) and antibiotic-related side effects (50.6% vs 46.1%, p = 0.42) were similar except prolonged prothrombin time (19.4% vs 6.4%; p = 0.001). According to this study results, CS and TZP have equal effectivity and safety for the empirical treatment of Gram-negative NIs. CS may be an appropriate alternative to TZP for antibiotic cycling or mixing strategy to reduce antibiotic resistance.

Short communication: Evaluation of α-linolenic acid-based intramammary nanosuspension for treatment of subclinical mastitis.

The current study investigates the therapeutic efficacy of an α-linolenic acid (ALA, 18:3n-3)-based intramammary nanosuspension (ALA-NS) for treatment of subclinical mastitis. After confirmation of mastitis with the help of field-based testing, a total of 9 mixed-breed cows (23 udder quarter samples) were divided into 3 groups and treated with ALA-NS and cefoperazone intramammary suspension for 10 d. Subclinical mastitis on d 1 was confirmed through field-based tests such as pH, California Mastitis Test (CMT), Whiteside test (WST), and bromothymol blue test (BBT) scores. Treatment with ALA-NS (F1 and F2) exhibited significant effects on field-based parameters, along with curtailment of total microbial count [28 ± 3.16 (mean ± standard deviation) and 25 ± 4.24 cfu/50 µL] and somatic cell count (SCC; 3.9 and 2.8 log SCC cells/mL), respectively for ALA-NS F1 and F2, after 10-d treatment. The efficacy of ALA-NS was further affirmed using more stringent markers for inflammation (nuclear factor kappa-light-chain-enhancer of activated B cells, NFκB-p65), milk quality (sterol response element-binding protein-1c, SREBP-1c), and bacterial resistance (ubiquitin carboxyl-terminal hydrolase-1, UCHL-1) in milk samples. Treatment with ALA-NS (at 2 concentrations of ALA, F1 and F2) significantly decreased expression of NFκB-p65, SREBP-1c, and UCHL-1 after d 10 of treatment. Apparently, anti-inflammatory, antibacterial, peripheral analgesic properties of ALA could account for the therapeutic efficacy of the proposed regimen.

Influence of some ß-lactam drugs on selected antioxidant enzyme and lipid peroxidation levels in different rat tissues.

Antioxidant enzymes play an important role in body defense and free radical removal. Cephalosporins are ß-lactam antibiotics. In this work, the effects of cefazolin, cefuroxime and cefoperazone which are cephalosporins on some selected antioxidant enzyme and levels of malondialdehyde (MDA) as lipid peroxidation product were investigated in kidney, liver, and brain tissues of albino female rats. Ninety-six albino rats were randomly divided into 16 groups of equal number (n = 6). 50 mg/kg cefazolin, 25 mg/kg cefuroxime, and 100 mg/kg cefoperazone were injected intraperitoneally to the groups (5th-8th and 9th-12th, and 13th-16th groups), respectively. The changes in glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GSH-Px) levels were studied in each time point group and a time-dependent manner (at the 1st, 3rd, 5th and 7th hour). In addition, MDA levels were examined in all the tissues. The drugs evaluated in this study had different effects on the same enzyme in different tissues depending on time. MDA levels especially in cefazolin and cefoperazone experiments were lower in all the tissues; however, MDA levels were higher in brain and kidney tissues in the cefuroxime groups in a time-dependent manner (p < 0.05). These results revealed the complex effects of the tested drugs on different tissues at different time points. Therefore, the dose and use of these drugs should be adjusted correctly.

Microbiota of MR1 deficient mice confer resistance against Clostridium difficile infection.

Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility.

Antibiotic-induced alterations in taurocholic acid levels promote gastrointestinal colonization of Candida albicans.

Candida albicans is a fungal pathogen that poses a significant public health risk due to high incidence and mortality rates among immunocompromised patients. Candida albicans infections begin with successful gastrointestinal (GI) colonization; however, the mechanisms behind this colonization remain to be elucidated. In this study, we investigated the role of taurocholic acid (TCA) on growth and GI colonization of C. albicans. Our results indicate that cefoperazone-treated mice susceptible to C. albicans infection had significantly increased levels of TCA in the gut contents. In addition, an increase in TCA levels directly correlates with higher C. albicans load in the fecal and gut contents of antibiotic-treated infected mice. Using in vitro assays, we also demonstrated that TCA enhances the growth of C. albicans and its ability to develop filamentous hyphae. Furthermore, TCA significantly increased the ability of C. albicans to attach to mammalian cells. These results demonstrate that antibiotic treatment alters TCA levels in the gut and potentially enhances GI colonization of C. albicans.

Multidrug-resistance Acinetobacter baumannii pneumonia in a rheumatoid arthritis patient receiving tumor necrosis factor inhibitor: A case report.

INTRODUCTION: Multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia with severe sepsis in a patient with rheumatoid arthritis (RA), who is predisposed after treatment with tumor necrosis factor inhibitor (TNFI), is a rare severe infection and can be successfully treated with prompt antibiotics. CASE PRESENTATION: A 75-year-old woman was diagnosed with RA >30 years previously. After inadequate treatment responses to conventional disease-modifying antirheumatic drugs (DMARDs), she developed progressive RA, including swollen joints in both hands, and had a high disease activity score of 4.96 when presenting at our rheumatology clinic. She had started taking the TNFI, golimumab (50 mg/month), 3 years before and developed a productive cough 4 weeks before this admission. One week after admission, she developed fever, dyspnea, hypoxemia, tachycardia, and increased serum C-reactive protein level. DIAGNOSIS: Chest plain film (CxR) and computed tomography of the chest showed hospital-acquired pneumonia; microbial examination of the sputum showed the presence of MDRAB. THERAPEUTICS: She was prescribed a full course of antibiotics with cefoperazone sulbactam. OUTCOMES: CxR showed complete remission of pneumonia. CONCLUSION: Biological DMARDs, such as TNFI, act as a double-edged sword: these drugs are used to treat autoimmune diseases, but they increase the risk of infection. The trend toward antibiotic resistance and persistent environmental survival of MDRAB is an emerging problem in countries with high rates of antibiotic abuse. TNFI may affect intestinal immunity by inducing dysbiosis, which affects T helper 17-mediated mucosal immunity and can contribute to A baumannii colonization and the development of MDRAB in frequently hospitalized patients.

Acute septic arthritis of shoulder joint caused by Aeromonas veronii biotype sobria.

We present the case of a 91-year-old woman who presented with a 2­day history of progressive pain and immobility of the right shoulder joint after fever of unknown etiology. Aeromonas sobria was isolated from a culture of purulent synovial fluid. The clinical condition gradually improved with the application of appropriate antibiotics and no surgical intervention was necessary. This report indicates that acute septic arthritis may result from Aeromonas veronii biotype sobria infections in healthy people. This case is contrary to the previous reports due to the absence of obvious risk factors.

Cefepime vs. cefoperazone/sulbactam in combination with amikacin as empirical antibiotic therapy in febrile neutropenia.

PURPOSE: Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN. METHODS: One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2 g q8h for adults and 50 mg/kg q8h for children) or CS (2 g q8h for adults and 50 mg/kg q8h for children) plus amikacin (15 mg/kg once a day). Positive response was defined as afebrile within 72 h of starting antibiotics, persistent afebrile status more than 48 h and no requirement of second-line antibiotics and antifungal agents. RESULTS: Three hundred thirty-six episodes were assessable for efficacy (168 cefepime, 168 CS + A). The positive response to antibiotics was identical for cefepime (53%) and CS + A (53%). Positive response was similar in MDI (microbiologically documented infection), 50 vs. 35% (p = 0.248), CDI (clinically documented infection), 50 vs. 35% (p = 0.259), combination CDI + MDI, 25 vs. 15% (p = 0.400), FUO (fever of unknown origin), 68 vs. 72% (p = 0.577) respectively in the two groups. The successful discontinuation of antibiotics at 72 h in FUO was similar in both groups (60 vs. 59%, p = 0.544). Total drug-related adverse events were similar in both groups (8 vs. 6%) except renal dysfunction was high in CS + A (1 vs. 7 events). Mortality was the same between two groups (8 vs 7%). CONCLUSIONS: Cefepime monotherapy and CS + A had similar efficacy as first-line therapy for FN. Discontinuation of empirical antibiotics is safe and feasible approach in selected group of FUO patients.

Comparison of the treatment efficacy between tigecycline plus high-dose cefoperazone-sulbactam and tigecycline monotherapy against ventilator-associated pneumonia caused by extensively drug-resistant Acinetobacter baumannii.

OBJECTIVE: The present study examined the effect of high-dose cefoperazone-sulbactam combined with tigecycline against ventilator-associated pneumonia (VAP) caused by extensively drug-resistant Acinetobacter baumannii(XDR-AB). MATERIALS AND METHODS: 42 patients with VAP due to XDR-AB infection were randomized into two groups: the TIG group (received tigecycline injection) and the TIG+CFS group (received tigecycline and cefoperazone-sulbactam (1 : 1) injection). Pulsed field gel electrophoresis (PFGE) was used for genotyping the isolated XDR-AB. The microdilution method was used to test the minimum inhibitory concentration (MIC) of cefoperazone-sulbactam or tigecycline in vitro and the combined effect was determined with the checkerboard method. RESULTS: The total combined effectiveness rate (including all patients who demonstrated an improved condition) was significantly higher in the TIG+CFS group (85.7%) compared with the TIG group (47.6%) (p = 0.010). No significant differences were noted with regard to the adverse reactions between the two groups. The 42 isolated XDR-AB strains were classified into four types. The MIC of the two drugs in combination was significantly lower than that of each drug used alone (p < 0.05). CONCLUSION: High dose of cefoperazone-sulbactam can improve the antimicrobial activity of tigecycline against XDR-AB.
.

A case of liver abscess co-infected with Desulfovibrio desulfuricans and Escherichia coli and review of the literature.

A 73-year-old woman was admitted with consciousness disturbance following a fever. Abdominal computed tomography revealed a large liver abscess with which the presence of Desulfovibrio desulfuricans and Escherichia coli was confirmed by thorough blood and abscess content culture. Empiric meropenem treatment was switched to cefoperazone/sulbactam, followed by ampicillin/sulbactam based on susceptibility testing. Desulfovibrio desulfuricans is a common bacterium that rarely causes liver abscess and may be overlooked during co-infection due to overgrowth of the accompanying bacteria. Clinicians should bear Desulfovibrio desulfuricans in mind and select the appropriate antibiotics according to susceptibility testing when anaerobic bacteria are detected in a liver abscess.