抗菌药物在腹腔感染中的合理应用

腹腔感染可分为社区获得性腹腔感染及医院获得性腹腔感染。腹腔感染的常见病原菌有肠杆菌科细菌、厌氧菌、链球菌、肠球菌、非发酵糖革兰阴性菌等。抗菌药物的使用是治疗腹腔感染的关键,抗菌药物的使用应结合腹腔感染的具体部位、严重程度、细菌与药物敏感状态的流行病学现状和抗菌药物的药效学和药代动力学特点等因素,选择合理的品种和正确的给药方法。     

Computed tomography-guided drainage of intra-abdominal infections

Image-guided percutaneous abscess drainage has become a standard method of treatment of most abdominal abscesses. In most cases, it should be considered the treatment of choice, but there are selected areas and circumstances that require specific approaches and methods. Typical abscesses within solid parenchyma organs or those in the peritoneal spaces can be reliably detected and efficiently drained. Abscesses that are multiple or long and circuitous require careful placement of catheters. Management of the drainage catheters includes irrigation with fluid to minimize accumulations of material that may impair egress of fluid. In selected cases, fibrinolytic agents have proved effective in shortening the drainage times and shortening hospital stays. Some controversial areas such as splenic abscesses, pancreatic abscesses, echinococcal abscesses, and fungal abscesses should only be attempted with careful selection and meticulous technique. Successful treatment is most likely with candid consultation among the various clinical services.     

Operative management of intra-abdominal infections.

Operation for intra-abdominal infection aims to prevent further contamination of the abdominal cavity, treat the underlying source of infection, and prevent residual or recurrent sepsis by cleaning the peritoneal cavity. Aggressive attempts at early diagnosis are warranted, even if laparotomy is occasionally required for diagnostic as well as therapeutic purposes. Conversely, the degree to which more aggressive methods of peritoneal debridement are helpful is the subject of great controversy that can be resolved only by prospective, randomized multicenter trials. Current standard treatment consists of closure, drainage, or excision of the source of contamination; intra-operative saline or antibiotic lavage of the peritoneal cavity; fascial closure; and secondary or delayed primary closure of the wound.     

New developments and concepts in antimicrobial therapy for intra-abdominal infections

Antimicrobial therapy plays an integral role in the management of intra-abdominal infections. Recent developments include increased prevalence of antimicrobial resistance (eg, Streptococcus pneumoniae and Enterococcus species) coupled with general decline in the antimicrobial susceptibility of anaerobes and gram-negative organisms, new antibiotics and dosing regimens, and better understanding of the role of various microbial pathogens and of prophylactic antimicrobial agents. Therapeutic approaches to intra-abdominal infections, such as the various forms of peritonitis, cholecystitis, cholangitis, and diverticulitis, are reviewed here. Specific recommendations for antimicrobial therapy in various clinical settings are provided, with special emphasis on recent trends and developments that reflect changes in understanding or therapy.     

Marine natural products and their potential applications as anti-infective agents

The oceans are a unique resource that provide a diverse array of natural products, primarily from invertebrates such as sponges, tunicates, bryozoans, and molluscs, and from marine bacteria and cyanobacteria. As infectious diseases evolve and develop resistance to existing pharmaceuticals, the marine environment provides novel leads against fungal, parasitic, bacterial, and viral diseases. Many marine natural products have successfully advanced to the late stages of clinical trials, including dolastatin 10, ecteinascidin-743, kahalalide F, and aplidine, and a growing number of candidates have been selected as promising leads for extended preclinical assessment. Although many marine-product clinical trials are for cancer chemotherapy, drug resistance, emerging infectious diseases, and the threat of bioterrorism have all contributed to the interest in assessing natural ocean products in the treatment of infectious organisms. In this review, we focus on the pharmacologically tested marine leads that have shown in-vivo efficacy or potent in-vitro activity against infectious and parasitic diseases.     

Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections

ABSTRACT Treatment of invasive fungal infections is increasingly complex. Amphotericin B deoxycholate has long been the mainstay of treatment. However, there has been increasing recognition of both the propensity for nephro-toxicity in haematology, transplant and intensive care patients as well as its adverse impact on morbidity and mortality. This has coincided with the availabilty of newer, and in certain settings, more effective antifungal agents. Although the newer agents clearly cause less nephrotoxicity than amphotericin B, drug interactions, hepatic effects and unique side-effects need to be considered. The spectrum of the newer triazoles and echinocandins varies, highlighting the importance of accurate identification of the causative organism where possible. Consensus Australian guidelines have been developed to assist clinicians with treatment choices by reviewing the current evidence for the efficacy, the toxicity and the cost of these agents.     

Ciprofloxacin vs. cefotaxime regimens for the treatment of intra-abdominal infections

Summary The efficacy of ciprofloxacin plus metronidazole was compared with that of cefotaxime plus gentamicin plus metronidazole in 79 patients with proven intra-abdominal infections. Patients were classified with the Peritonitis Index Altona-II (PIA-II) score for severity of disease, underlying conditions, prognosis and type of infection. Local peritonitis was diagnosed in 21 patients, generalized peritonitis in 25, intra-abdominal abscesses in 33; 35 patients had polymicrobial infections. Cure and improvement rates were: ciprofloxacin 77%, cefotaxime combination 56% (p<0.02). Failures were significantly associated with a low initial PIA-II score, the presence of generalized peritonitis or abscesses, persistence of pathogens and superinfection. Superinfection was observed in 49% of the cases under cefotaxime and in 30% under ciprofloxacin. Concentrations of ciprofloxacin in pus ranged 2.0–5.2 mg/l with simultaneous serum concentrations of 1.2–3.1 mg/l.

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Behandlung intraabdomineller Infektionen mit Ciprofloxacin im Vergleich zu einem Cefotaxim-haltigen Regime

Zusammenfassung Die Wirksamkeit der Kombination Ciprofloxacin-Metronidazol wurde mit der Kombination Cefotaxim plus Gentamicin plus Metronidazol bei 79 Patienten mit erwiesener intraabdomineller Infektion verglichen. Der Schweregrad der Erkrankung wurde nach dem Peritonitis-Index Altona-II (PIA-II)-Score klassifiziert, erfaßt wurden außerdem Grundkrankheiten, Prognose und Art der Infektion. Eine lokale Peritonitis lag bei 21 Patienten vor, eine generalisierte Peritonitis bei 25. In 33 Fällen fanden sich intraabdominelle Abszesse. In 35 Fällen handelte es sich um eine polymikrobielle Infektion. Die Rate an Heilungen und Besserungen betrug bei Patienten, die Ciprofloxacin erhalten hatten, 77%, bei Patienten, die mit der Cefotaxim-Kombination behandelt wurden, 56% (p<0,02). Eine signifikante Korrelation zu Therapieversagen bestand mit einem niedrigen initialen PIA-II-Score, dem Vorliegen einer generalisierten Peritonitis oder Abszessen, der Erregerpersistenz und einer Superinfektion. In 49% der mit Cefotaxim behandelten und bei 30% der mit Ciprofloxacin behandelten Fälle wurden Superinfektionen beobachtet. Die Konzentrationen von Ciprofloxacin im Eiter lagen in einem Bereich von 2,0–5,2 mg/l bei zeitgleichen Serumkonzentrationen von 1,2–3,1 mg/l.

     

Systematic review and meta-analysis of the use of serum procalcitonin levels to predict intra-abdominal infections after colorectal surgery

Purpose

There has been much recent interest in the use of procalcitonin (PCT) as a marker of intra-abdominal infection (IAI) following colorectal surgery. However, the literature remains divided on the value of PCT in this setting. This meta-analysis aims to evaluate the value of PCT in predicting IAI after colorectal surgery.

Methods

Systemic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews to identify studies evaluating the diagnostic accuracy of PCT as a predictor for detecting IAI on postoperative days (POD) 3 to 5 following colorectal surgery. A meta-analysis was performed using random effect model and pooled predictive parameters as well as cut-off values for POD 3 to 5 were derived.

Results

Eight studies consisting 1629 patients were included. The pooled prevalence of IAI was 5.7% on POD 3, 9.7% on POD 4, and 6.3% on POD 5. The pooled AUC for POD 3 to 5 were 0.83 (95% CI 0.78–0.88), 0.79 (95% CI 0.64–0.93), and 0.94 (95% CI 0.91–0.97), respectively. The derived PCT cut-off values were 1.45 ng/ml on POD 3, 1.28 ng/ml on POD 4, and 1.26 ng/ml on POD 5. PCT had the highest diagnostic capability on POD 5 with diagnostic odds ratio of 32.9 (95% CI 15.01–69.88), sensitivity of 0.78 (95% CI 0.65–0.89), and specificity of 0.88 (95% CI 0.85–0.90).

Conclusions

PCT is a useful diagnostic predictor of IAI after colorectal surgery. It has the greatest diagnostic accuracy on POD 5 and can help guide safe discharge of patients after colorectal surgery.

     

Antimicrobial management of intra-abdominal infections: literature's guidelines

Antimicrobial management of severe intra-abdominal infections (IAIs) involves a delicate balance of optimizing empirical therapy, which has been shown to improve clinical outcomes, while simultaneously reducing unnecessary antimicrobial use. Two sets of guidelines for the management of intra-abdominal infections were recently published. In 2010, the Surgical Infection Society and the Infectious Diseases Society of America (SIS-IDSA) created guidelines for the diagnosis and management of complicated IAIs. The new SIS-IDSA guidelines replace those previously published in 2002 and 2003. The World Society of Emergency Surgery (WSES) guidelines represent additional contributions, made by specialists worldwide, to the debate regarding proper antimicrobial drug methodology. These guidelines represent the conclusions of the consensus conference held in Bologna, Italy, in July 2010 during the first congress of the WSES.     

鸟分枝杆菌复合群对16种抗感染药物药敏试验的分析

目的 通过比较3种新型喹诺酮类药物(西他沙星、加替沙星和莫西沙星)与其他13种抗感染药物对鸟分枝杆菌复合群(MAC)分离株的体外活性,初步探讨喹诺酮类药物用于治疗MAC疾病的可能性.方法 琼脂梯度稀释法测定上述16种抗感染药物对MAC分离株的最低抑菌浓度(MIC),比较其能抑制90%菌株生长的MIC(MIC90).结果 与胞内分枝杆菌相比,鸟分枝杆菌菌株的MIC范围分布更广,且MIC90多高于胞内分枝杆菌.4种大环内酯类药物中,克拉霉素对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,分别为32和16 mg/L;4种利福霉素类化合物中利福拉齐对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,分别为0.5和0.25 mg/L;5种喹诺酮类药物中西他沙星对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,均为4 mg/L,加替沙星和莫西沙星均为8 mg/L.2株克拉霉素敏感株(MIC=0.5 mg/L)对其他抗感染药物均接近或达到MIC范围的下限,3株克拉霉素不敏感株(MIC=64 mg/L)对除喹诺酮类以外的抗感染药物均接近MIC范围的上限.结论 利福拉齐、西他沙星、加替沙星和莫西沙星对MAC分离株具有较强的体外活性.     

New antimicrobial agents for Gram-positive infections

Increasing antimicrobial resistance in Gram-positive bacteria has presented a formidable treatment problem. The enterococci, although traditionally non-virulent pathogens, have been shown, when associated with vancomycin resistance, to have an attributable mortality of approximately 40%. The frightening specter of widespread vancomycin resistance in the more virulent Staphylococcus aureus would have a significantly greater impact. Since the late 1980s, advances have been made in the development of pharmacological weapons against multiply resistant Gram-positive bacterial infections. At least seven new antimicrobial classes that have activity against resistant Gram-positive organisms are in various stages of development. Most are semisynthetic derivatives of known antibiotics; however, importantly, a unique class of antimicrobial agent has also emerged.     

Meropenem monotherapy versus cefotaxime plus metronidazole combination treatment for serious intra-abdominal infections

Summary In an open, randomised, multicentre trial, the efficacy and tolerability of empirical meropenem monotherapy (1 g intravenously every 8 hours) and cefotaxime (2 g every 8 hours) plus metronidazole (0.5 g intravenously every 8 hours) for 5 to 10 days was compared in 94 patients with serious intra-abdominal infection who required surgery. Eighty-three patients had an evaluable clinical response. Significantly more patients in the meropenem group had a satisfactory clinical response at the end of treatment (41/43 [95.3%] vs 30/40 [75.0%]; p=0.008). The bacteriological response was also higher in the meropenem group (31/33 vs 26/32). In the bacteriologically evaluable population, a satisfactory clinical response was observed in 31/33 of those who received meropenem compared to 24/32 of the cefotaxime/metronidazole recipients (p=0.03). Empirical meropenem monotherapy should prove a useful alternative to the currently standard combination treatment for serious intraabdominal infections.

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Meropenem Monotherapie im Vergleich zu Cefotaxim plus Metronidazol in der Therapie schwerer intraabdomineller Infektionen

Zusammenfassung In einer offenen, randomisierten Multicenter-Studie wurden die Wirksamkeit und Verträglichkeit einer initialen Monotherapie mit Meropenem (MEM, 1 g 3 × tägl. i.v.) mit der etablierten Kombinationstherapie Cefotaxim (CTX) plus Metronidazol (MTR) (2 g CTX+0.5 g MTR 3×tägl. i.v.) verglichen. 94 Patienten mit operationspflichtigen schweren intraabdominellen Infektionen wurden einbezogen. Davon waren 83 Patienten bezüglich klinischem Ansprechen auswertbar. Die klinische Wirksamkeit war in der MEM-Gruppe signifikant höher (41/43 Pat.=95.3% vs 30/40 Pat.=75%; p=0.008). Das bakteriologische Ansprechen war in der MEM-Gruppe ebenfalls höher im Vergleich zur Kombinationsgruppe (31/33 vs 26/32), der Unterschied war jedoch statistisch nicht signifikant. In der bakteriologisch auswertbaren Population war das klinische Ansprechen in der MEM-Gruppe signifikant höher als im Vergleichskollektiv (31/33 vs 24/32; p=0.03). MEM erscheint somit für die initiale empirische Monotherapie bei schweren intraabdominellen Infektionen geeignet.

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On behalf of the German Peritonitis Study Group: Dr.Griesenbeck, Prof. Dr.Wendling, Prof. Dr.Männl, Prof. Dr.Rückert, Germany.     

Utility of fibrinolytic agents for draining intrapleural infections

Multiple studies have shown that the intrapleural instillation of fibrinolytic agents provides an effective and safe mode of treatment for complicated parapneumonic effusions and empyemas that decrease the need for surgical interventions. Although most investigators use streptokinase and urokinase, the technique of instillation is not standardized. The usual dose of streptokinase is 250,000 IU, but doses range from 50,000 to 220,000 IU for urokinase. Reported success rates range from 38% to 100%, but outcomes depend on the stage of progression of the parapneumonic effusion when fibrinolytics are employed. Fibrinolytics are more effective in complicated parapneumonic effusions than in established empyemas. Although complications of fibrinolytic therapy rarely occur, they result most often from allergic reactions to streptokinase. Urokinase is safer but more expensive. More randomized, comparative, controlled studies are needed to further define the most effective mode of fibrinolytic therapy for subgroups of patients with pleural infection.