Antibiotic treatment

抗生素治疗
  • 文章类型: Journal Article
    目的:探讨既往参与临床研究是否能提高急性非复杂性憩室炎(AUD)患者对治疗指南的依从性。
    方法:这项回顾性队列研究旨在对六家医院的AUD管理进行快照,其中3例参与了AVOD试验,比较了抗生素和非抗生素对AUD的治疗.从2019年3月至2020年6月纳入AUD患者,随访90天。主要结果是与AVOD和非AVOD医院相比,按抗生素治疗和住院或门诊管理分类的AUD治疗。编制了描述性统计数据,医院之间的差异用皮尔森卡方检验进行评估。
    结果:该队列包括449例AUD患者,其中63%为女性,中位年龄为63(IQR:52-73)岁。不同医院的患者特征具有可比性。84例(19%)患者服用抗生素,113例(25%)患者作为住院患者进行管理。AVOD和非AVOD医院之间的管理差异很大。AVOD医院接受抗生素治疗的患者平均比例为7%,而非AVOD医院为38%(p<0.001)。AVOD医院内管理的平均比例为18%,非AVOD医院为38%(p<0.001)。
    结论:大多数AUD患者根据当前指南进行治疗。然而,医院之间的管理不同,以前参与临床研究可能会增加对指南的了解和依从性.
    OBJECTIVE: To explore whether previous participation in clinical studies increases adherence to management guidelines in acute uncomplicated diverticulitis (AUD).
    METHODS: This retrospective cohort study was designed to give a SNAPSHOT of the management of AUD at six hospitals, three of which had participated in the AVOD trial comparing antibiotic versus non-antibiotic treatment of AUD. Patients with AUD were included from March 2019 through June 2020 and followed for 90 days. The primary outcome was treatment of AUD categorised by antibiotic treatment and inpatient or outpatient management compared between AVOD and non-AVOD hospitals. Descriptive statistics were compiled, and differences between hospitals were assessed with Pearson\'s chi-squared test.
    RESULTS: The cohort included 449 patients with AUD of which 63% were women and the median age was 63 (IQR: 52-73) years. Patient characteristics were comparable across the hospitals. Antibiotics were administered to 84 (19%) patients and 113 (25%) patients were managed as inpatients. Management varied significantly between AVOD and non-AVOD hospitals. The mean proportion of patients treated with antibiotics was 7% at AVOD hospitals compared to 38% at non-AVOD hospitals (p < 0.001). The mean proportion of in-hospital management was 18% at AVOD hospitals versus 38% at non-AVOD hospitals (p < 0.001).
    CONCLUSIONS: Most patients with AUD were managed according to current guidelines. However, the management varies between hospitals and previous participation in clinical studies may increase knowledge of and adherence to guidelines.
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  • 文章类型: Journal Article
    高通量测序研究表明,饮食或抗微生物治疗会影响动物肠道微生物群平衡。然而,与肠道微生物生态系统稳定性相关的特性,比如韧性,阻力,或功能冗余,必须更好地理解。为了阐明这些生态过程,我们将先进的统计方法与16SrRNA基因测序相结合,功能预测,和适应度分析,在受到抗生素(AB)卡那霉素(n=512)的三个周期性脉冲的德国蟑螂小孢子的肠道微生物群。我们首先确认AB并没有显著影响蟑螂的生物适应性,肠道微生物群的变化不是由昆虫生理改变引起的。首次在该物种中检查了性别变量,在肠道菌群多样性或组成方面没有发现统计学差异。对照和治疗人群的肠道微生物群动态比较表明,(1)AB治疗降低了多样性,并完全破坏了细菌之间的共现网络,显著改变肠道群落结构。(2)虽然AB也影响了遗传组成,功能冗余将解释对功能潜力的影响小于对分类组成的影响。(3)正如泰勒定律所预测的那样,AB通常对最丰富的类群的影响程度小于不太丰富的类群。(4)分类群对ABs的反应遵循不同的趋势,突出“抗性分类群”,“这对社区恢复至关重要。(5)三个AB脉冲后,肠道菌群恢复更快,这表明肠道微生物群适应重复治疗。
    High-throughput sequencing studies have shown that diet or antimicrobial treatments impact animal gut microbiota equilibrium. However, properties related to the gut microbial ecosystem stability, such as resilience, resistance, or functional redundancy, must be better understood. To shed light on these ecological processes, we combined advanced statistical methods with 16 S rRNA gene sequencing, functional prediction, and fitness analyses in the gut microbiota of the cockroach Blattella germanica subject to three periodic pulses of the antibiotic (AB) kanamycin (n=512). We first confirmed that AB did not significantly affect cockroaches\' biological fitness, and gut microbiota changes were not caused by insect physiology alterations. The sex variable was examined for the first time in this species, and no statistical differences in the gut microbiota diversity or composition were found. The comparison of the gut microbiota dynamics in control and treated populations revealed that (1) AB treatment decreases diversity and completely disrupts the co-occurrence networks between bacteria, significantly altering the gut community structure. (2) Although AB also affected the genetic composition, functional redundancy would explain a smaller effect on the functional potential than on the taxonomic composition. (3) As predicted by Taylor\'s law, AB generally affected the most abundant taxa to a lesser extent than the less abundant taxa. (4) Taxa follow different trends in response to ABs, highlighting \"resistant taxa,\" which could be critical for community restoration. (5) The gut microbiota recovered faster after the three AB pulses, suggesting that gut microbiota adapts to repeated treatments.
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  • 文章类型: Journal Article
    背景:研究的目的是表征外周静脉治疗(IT)的程序,包括血管通路和相关并发症的特点以及药物消耗的定性和定量分析。
    方法:两年,回顾性,进行单中心观察性研究.将患者纳入研究的标准是入院时或在内科(IMD)住院期间使用外周静脉导管(PIVC)。
    结果:住院的主要原因是78%的患者因慢性疾病加重和22%的急性感染。83.6%的患者使用了IT。IT主要用于抗生素(5009.9定义的日剂量(DDD))。Further,22.6%的PIVC在24小时内停止运作,在感染患者中更常见。PIVC去除的主要原因是泄漏(n=880,26.6%)和闭塞(n=578,17.5%)。PIVC位置大多次优(n=2010,59.5%),这些位置与渗漏和闭塞有关(p=0.017).
    结论:在IMD中,大多数患者需要使用PIVC,抗生素在静脉注射药物中占主导地位。在插入后的最初24小时内,多达1/5的外周静脉导管丢失,他们中的大多数都放置得不够理想。正常工作的PIVC似乎对于抗菌治疗至关重要。
    BACKGROUND: The aim of the study was to characterize the procedure of peripheral intravenous therapy (IT), including the characteristics of vascular access and related complications and qualitative and quantitative analyses of drug consumption.
    METHODS: A two-year, retrospective, single-center observational study was conducted. The criterion for including a patient in the study was the use of peripheral intravenous catheters (PIVCs) upon admission or during the stay at the internal medicine department (IMD).
    RESULTS: The main reasons for hospitalization were exacerbations of chronic diseases for 78% of the patients and acute infections for 22%. IT was used in 83.6% of all the patients. IT was used primarily for antibiotics (5009.9 defined daily doses (DDD)). Further, 22.6% of the PIVCs stopped functioning within 24 h, more frequently in infectious patients. The main reasons for PIVC removal were leakage (n = 880, 26.6%) and occlusion (n = 578, 17.5%). The PIVC locations were mostly suboptimal (n = 2010, 59.5%), and such locations were related to leakage and occlusion (p = 0.017).
    CONCLUSIONS: In the IMD, most patients require the use of a PIVC, and antibiotics dominate the group of drugs administered intravenously. Up to 1/5 of peripheral intravenous catheters are lost within the first 24 h after their insertion, with most of them placed suboptimally. A properly functioning PIVC appears to be crucial for antimicrobial treatment.
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  • 文章类型: Journal Article
    这项回顾性研究旨在评估和比较2019年1月至2020年12月德国三级医院尿路感染(UTI)和血流感染(BSIs)管理的指南依从性和治疗成本。该研究分析了586份患者记录,65%诊断为UTI,35%诊断为BSI。98%的患者接受了抗生素治疗,但只有65%的人接受了微生物诊断。在86%的培养物患者中观察到细菌生长,大肠杆菌是主要的病原体。63%的病例采用静脉注射治疗,头孢曲松是主要的抗生素。发现指南的依从性很低,33%。多变量logistic回归分析显示,有泌尿生殖道危险因素(OR=1.589;p<0.001)和年龄增加(OR=1.01;p=0.007)的患者更有可能接受指南一致的UTI和BSI治疗。此外,糖尿病和肾功能障碍等复杂因素与更高的依从性相关,强调有针对性的抗生素管理干预措施的重要性。
    This retrospective study aimed to assess and compare guideline adherence and treatment costs in the management of urinary tract infections (UTIs) and bloodstream infections (BSIs) in German tertiary hospitals from January 2019 to December 2020. The study analyzed 586 patient records, with 65% diagnosed with UTIs and 35% with BSIs. Antibiotic treatment was given to 98% of patients, but only 65% received microbiological diagnostics. Bacterial growth was observed in 86% of patients with cultures taken, with Escherichia coli being the leading pathogen. The treatment was intravenous in 63% of cases, with Ceftriaxone as the leading antibiotic agent. The guideline adherence was found to be low, at 33%. Multivariable logistic regression analysis revealed that patients with urogenital risk factors (OR = 1.589; p < 0.001) and increasing age (OR = 1.01; p = 0.007) were significantly more likely to receive guideline-concordant treatment for UTIs and BSIs. Additionally, complicating factors such as diabetes and renal dysfunction were associated with higher adherence rates, underscoring the importance of targeted antibiotic stewardship interventions.
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  • 文章类型: Case Reports
    在接受万古霉素治疗的患者中,常规监测血清药物水平以确保治疗剂量并将毒性降至最低.在极少数情况下,万古霉素水平可能错误或持续升高,没有任何明显原因。在这个案例报告中,我们探索了一例罕见的万古霉素水平持续升高的病例,尽管停药数天.这是一例69岁的女性,因腿部蜂窝织炎败血症继发的精神状态改变而入院。抗生素治疗包括万古霉素。为了确保正确的剂量,在第四剂之前收集万古霉素谷水平,结果显示39ug/ml的高值。万古霉素剂量根据贝叶斯给药软件进行调整,和相同的仍然是超治疗水平。病人最终病情恶化,由于万古霉素水平持续高,抗生素治疗方案改为另一种抗生素.尽管肾功能正常,万古霉素水平仍然很高,在27ug/ml和32ug/ml之间,即使没有任何进一步的剂量。随后,万古霉素血清浓度通过另一种方法使用高效液相色谱法(HPLC)测定。血液培养物既生长了凝固酶阴性的金黄色葡萄球菌,又生长了木氧嗜酸性杆菌。万古霉素水平在停药一周后仍然很高。万古霉素经HPLC检测最终显示万古霉素在血液中检测不到,但是,不幸的是,结果是在患者已经过期的时候得出的。总之,如果万古霉素水平持续升高不能由肾功能或其他原因引起,临床医师应高度怀疑.在万古霉素水平持续升高并持续临床恶化的患者中,至关重要的是要考虑到分析干扰会导致万古霉素水平不准确升高。
    In patients receiving vancomycin therapy, serum drug levels are routinely monitored to ensure therapeutic dosing and minimize toxicity. In rare cases, vancomycin levels may be falsely or persistently elevated without any apparent cause. In this case report, we explore a rare case of persistently elevated vancomycin levels despite discontinuation of the drug for days.  This is a case of a 69-year-old female admitted for altered mental status secondary to sepsis from leg cellulitis. Antibiotic therapy included vancomycin. To ensure proper dosing, vancomycin trough levels were collected before the fourth dose, and the result showed a high value of 39 ug/ml. Vancomycin doses were adjusted as per the Bayesian dosing software, and the same remained to be in supratherapeutic levels. The patient eventually deteriorated, and due to persistently high vancomycin levels, the antibiotic regimen was switched to a different antibiotic. Despite normal renal functions, the vancomycin levels remained high, between 27 ug/ml and 32 ug/ml, even in the absence of any further doses. Subsequently, vancomycin serum concentration was determined by another method using high-performance liquid chromatography (HPLC). Blood cultures grew both coagulase-negative Staphylococcus aureus and Achromobacter xylosoxidans. Vancomycin levels remained high a week after discontinuation of the drug. Vancomycin by HPLC assay eventually showed that vancomycin was undetectable in the blood, but, unfortunately, the results came at a time when the patient had already expired. In conclusion, clinicians should maintain a high level of suspicion if persistently higher vancomycin levels cannot be accounted for by renal function or other causes. In patients with persistently high vancomycin levels who continue to clinically deteriorate, it is crucial to consider that assay interference can result in inaccurately elevated vancomycin levels.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Case Reports
    咽后脓肿(RPAs)在成年人群中很少见,并且很少见,没有煽动事件或合并症,例如最近的口腔手术,颈部感染,或者咽部外伤.最终的治疗方法是脓肿的切开和引流。临床研究人员最近质疑侵入性手术干预是否必要,并提出了抗生素在管理中起什么作用的问题。RPA的后遗症很严重,包括脓肿破裂,颈动脉的侵蚀,血栓性静脉炎,最严重的是,气道损害。我们提出了一个案例,其中RPA的非典型介绍引起了专家之间的分歧,以及所描述的病例是否代表脓肿或恶性肿瘤的争论导致了患者诊断和治疗的延迟。只有经过侵入性和紧急手术干预后,才能做出最终诊断。这个案例表明需要对新颈部肿块的管理进行更多的研究和官方指导,以加快诊断并防止破坏性后果。
    Retropharyngeal abscesses (RPAs) are rare in the adult population and rarer without an inciting event or comorbidity such as recent oral surgery, neck infection, or pharyngeal trauma. The definitive treatment is incision and drainage of the abscess. Clinical researchers have recently questioned whether invasive surgical intervention is necessary and posed the question of what role antibiotics play in management. Sequelae of RPAs are severe and include rupture of the abscess, erosion of the carotid artery, thrombophlebitis, and most seriously, airway compromise. We present a case where an atypical presentation of an RPA caused a disagreement among specialists, and the debate of whether the described case represented an abscess or malignancy caused a delay in diagnosis and treatment for the patient. Only after invasive and emergent surgical intervention was a final diagnosis able to be made. This case demonstrates the need for more research and official guidance on the management of new neck masses to hasten diagnosis and prevent devastating outcomes.
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  • 文章类型: Case Reports
    在囊性纤维化微生物学中,分离的细菌病原体的抗生素敏感性结果与临床结果之间通常不匹配,当患者使用相同的抗生素治疗时。这方面的推理在很大程度上仍然难以捉摸。抗生素对四种抗生素的敏感性(头孢他啶,美罗培南,在成年囊性纤维化患者的连续分离株(n=11)中确定了米诺环素和甲氧苄啶-磺胺甲恶唑),超过63个月。每种分离物显示其自己独特的抗性型。第一个分离株对所有四种抗生素都敏感,根据临床和实验室标准研究所的方法和解释标准。四个月时首次检测到耐药性,对头孢他啶和美罗宁具有抗性,对米诺环素和甲氧苄啶-磺胺甲恶唑具有中等抗性。Pan抗性在18个月时首次检测到(抗性IV型),具有三种抗性型(I,II和III)在该完全抗性型之前。在接下来的45个月中,该细菌继续显示出进一步的抗生素敏感性异质性,并描述了另外7种抗性型(抗性型V-XI)。该细菌在63个月期间的相对抗性指数显示抗生素抗性的发展与时间之间没有关系。采用多项分布的数学模型表明,大量的个体菌落采摘(>40/痰),将需要78%的信心捕获存在的所有11个抗性型。对大量菌落的需求与与抗生素敏感性相关的方法学问题相结合,在生物医学科学实践中产生了一个难题。在提供一个强大的检测,将捕获抗生素易感性的变化,务实且具有成本效益的提供病理服务,但具有帮助临床医生为患者选择合适的抗生素的可靠性。这项研究代表了生物医学科学的进步,因为它证明了伯克霍尔德氏菌对ciocepacia的抗生素敏感性测试的潜在变异性。呼吸科医生和儿科医生需要让生物医学科学家意识到这种变化,以便临床医生可以将报告的易感性结果的重要性置于上下文中,当为囊性纤维化患者选择合适的抗生素时。此外,需要考虑在实验室报告中提供额外的指导,以强调这种异质性,从而强调易感性结果和临床结局之间可能存在不一致.
    Within cystic fibrosis microbiology, there is often mismatch between the antibiotic susceptibility result of an isolated bacterial pathogen and the clinical outcome, when the patient is treated with the same antibiotic. The reasoning for this remains largely elusive. Antibiotic susceptibility to four antibiotics (ceftazidime, meropenem, minocycline and trimethoprim-sulfamethoxazole) was determined in consecutive isolates (n = 11) from an adult cystic fibrosis patient, over a 63 month period. Each isolate displayed its own unique resistotype. The first isolate was sensitive to all four antibiotics, in accordance with Clinical and Laboratory Standards Institute methodology and interpretative criteria. Resistance was first detected at four months, showing resistance to ceftazidime and meropenen and intermediate resistance to minocycline and trimethoprim-sulfamethoxazole. Pan resistance was first detected at 18 months (resistotype IV), with three resistotypes (I, II and III) preceding this complete resistotype. The bacterium continued to display further antibiotic susceptibility heterogeneity for the next 45 months, with the description of an additional seven resistotypes (resistotypes V-XI). The Relative Resistance Index of this bacterium over the 63 month period showed no relationship between the development of antibiotic resistance and time. Adoption of mathematical modelling employing multinomial distribution demonstrated that large numbers of individual colony picks (>40/sputum), would be required to be 78% confident of capturing all 11 resistotypes present. Such a requirement for large numbers of colony picks combined with antibiotic susceptibility-related methodological problems creates a conundrum in biomedical science practice, in providing a robust assay that will capture antibiotic susceptibility variation, be pragmatic and cost-effective to deliver as a pathology service, but have the reliability to help clinicians select appropriate antibiotics for their patients. This study represents an advance in biomedical science as it demonstrates potential variability in antibiotic susceptibility testing with Burkholderia cenocepacia. Respiratory physicians and paediatricians need to be made aware of such variation by biomedical scientists at the bench, so that clinicians can contextualise the significance of the reported susceptibility result, when selecting appropriate antibiotics for their cystic fibrosis patient. Furthermore, consideration needs to be given in providing additional guidance on the laboratory report to highlight this heterogeneity to emphasise the potential for misalignment between susceptibility result and clinical outcome.
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  • 文章类型: Journal Article
    梅毒,一种普遍的性传播感染,构成严重风险,尤其是在怀孕期间。本研究旨在阐明广西梅毒流行趋势和影响,中国,专注于患病率,临床表现,以及孕妇和新生儿的治疗结果。目标包括了解受影响孕妇的人口特征,分析新生儿的临床表现,并评估治疗方案的有效性。
    遵守道德准则,2013年1月至2023年12月的一项回顾性队列研究纳入了54,048名接受梅毒螺旋体检测的孕妇.诊断涉及全面的方法,利用测试如甲苯胺红不加热血清测试(TRUST)和梅毒螺旋体颗粒凝集(TPPA)测定。通过长达十年的随访评估了婴儿的诊断和临床表现。治疗方案,包括苄星青霉素,已实施。使用SAS版本9.4进行统计分析。
    在54,048名孕妇中,0.10%为梅毒阳性,与住院率上升有关。新生儿表现出不同的临床表现,新生儿肺炎和黄疸很普遍。治疗方案,尤其是苄星青霉素,取得了显著的100%治愈成功率。该研究指出,母婴传播显着减少。母亲和婴儿的梅毒在不同的临床阶段被诊断出来,包括主要的,次要,潜在的,和第三。
    这项研究强调了梅毒对广西孕妇和新生儿的影响,中国。调查结果强调了采取强有力的预防措施的必要性,早期诊断,和有效的治疗策略。观察到的100%使用苄星青霉素的治愈成功率强调了严格治疗方案在减轻先天性梅毒的不良反应和减少其传播方面的重要性。
    UNASSIGNED: Syphilis, a prevalent sexually transmitted infection, poses severe risks, especially during pregnancy. This study aimed to elucidate the trends and impacts of syphilis in Guangxi, China, focusing on prevalence, clinical manifestations, and treatment outcomes in pregnant women and newborns. The objectives included understanding the demographic characteristics of affected pregnant women, analysing the clinical manifestations in newborns, and assessing the effectiveness of the treatment protocol.
    UNASSIGNED: Conducted in adherence to ethical guidelines, a retrospective cohort study from January 2013 to December 2023 included 54,048 pregnant women tested for T. pallidum. Diagnosis involved a comprehensive approach, utilizing tests like the Toluidine Red Unheated Serum Test (TRUST) and the Treponema pallidum Particle Agglutination (TPPA) assay. Infant diagnosis and clinical manifestations were evaluated through a decade-long follow-up. Treatment protocols, including Benzathine penicillin, were implemented. Statistical analyses were conducted using SAS version 9.4.
    UNASSIGNED: Among 54,048 pregnant women, 0.10% were syphilis positive, correlating with a rise in hospitalizations. Newborns exhibited varied clinical manifestations, with neonatal pneumonia and jaundice being prevalent. The treatment protocol, especially with Benzathine penicillin, achieved a remarkable 100% cure success rate. The study noted a significant reduction in mother-to-child transmission. Syphilis in mothers and babies was diagnosed at different clinical stages, including primary, secondary, latent, and tertiary.
    UNASSIGNED: This study underscores the escalating impact of syphilis on pregnant women and newborns in Guangxi, China. The findings highlight the necessity for robust preventive measures, early diagnosis, and effective treatment strategies. The observed 100% cure success rate with Benzathine penicillin emphasizes the importance of strict treatment protocols in mitigating the adverse effects of congenital syphilis and reducing its transmission.
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  • 文章类型: Journal Article
    Pyometra是一种细菌性子宫感染,经常影响完整的老年母犬。选择的治疗方法是卵巢子宫切除术,常与围手术期抗菌治疗相关。这项回顾性调查的目的是评估不同给药时间的抗生素选择(手术前,在手术/住院期间,和手术后)针对并发症和结果,考虑到细菌的敏感性。51只母犬的医疗记录转诊到都灵大学兽医教学医院(2021年1月至2023年11月),并接受卵巢子宫切除术和子宫渗出物的细菌学检查(细菌培养和药敏试验),进行了分析。所有动物都有积极的结果,没有手术部位感染,在腹膜炎或败血症的情况下,住院时间更长;平均服用抗生素7天。比较分离的细菌对之前施用的抗微生物剂的敏感性,手术期间和之后,在42%中观察到完全疗效,46%和50%的病例,分别。此外,5/16例腹膜炎病例采用体外无效抗菌药物治疗,30%的母狗从未接受过完全有效的抗生素,根据药敏试验采用最小抑制浓度法(MIC)。头孢唑林是大肠杆菌的最佳选择,最常见的细菌。我们的研究证实卵巢子宫切除术和抗生素给药后子宫积脓具有良好的预后。在不复杂的病例中,监测临床演变而不根据细菌敏感性改变抗生素可能是正确的选择。在没有术后抗菌治疗或病程较短的情况下评估结果将是另一个值得研究的主题,目的是明智地减少抗生素的使用。
    Pyometra is a bacterial uterine infection that frequently affects intact older bitches. The treatment of choice is ovariohysterectomy, often associated with perioperative antimicrobial therapy. The aim of this retrospective investigation was to evaluate the antibiotic choice at different administration times (pre-surgery, at surgery/during hospitalization, and post-surgery) against complications and outcomes, considering the susceptibility profile of bacteria. The medical records of 51 bitches referred to the Veterinary Teaching Hospital of the University of Turin (January 2021-November 2023) and subjected to ovariohysterectomy and bacteriological examination (bacterial culture and susceptibility tests) of the uterine exudate, were analysed. All animals had a positive outcome without surgical site infections, with a longer hospitalization time in case of peritonitis or sepsis; antimicrobials were administered for an average of 7 days. Comparing the susceptibility of the isolated bacteria towards the antimicrobials administered before, during and after surgery, complete efficacy was observed in 42 %, 46 % and 50 % of cases, respectively. In addition, 5/16 peritonitis cases were treated with an in vitro ineffective antimicrobial, and 30 % of the bitches never received a fully effective antibiotic, according to susceptibility tests using the minimum inhibitory concentration method (MIC). Cephazolin resulted the best option for Escherichia coli, the most frequently isolated bacterium. Our study confirms that pyometra has a good prognosis following ovariohysterectomy and antibiotic administration. Monitoring the clinical evolution without changing the antibiotic according to bacterial susceptibility could represent the right choice in uncomplicated cases. Evaluation of outcomes without postoperative antibacterial treatment or with a shorter course would be another topic worth investigating, with the aim to judiciously reduce the use of antibiotics.
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