Treatment Of Anaerobic Infections Research Articles

Ornidazole Transfer into Colostrum and Assessment of Exposure Risk for Breastfeeding Infant: A Population Pharmacokinetic Analysis.

Ornidazole is frequently used for the prevention and treatment of anaerobic infections after caesarean section. There is still a lack of data on the excretion of ornidazole in breast milk. Therefore, the aim of this study was to investigate the transfer of ornidazole into colostrum and to assess the risk of infant exposure to the drug via breast milk. Population pharmacokinetic analysis was conducted using datasets of plasma and milk concentrations obtained from 77 breastfeeding women to examine the excretion kinetics of ornidazole. Various factors that may affect the excretion of ornidazole were investigated. The final model was then used to simulate ornidazole concentration-time profiles in both plasma and milk. The drug exposure in body fluids and the potential risk for breastfeeding were assessed based on the safety threshold. Plasma ornidazole concentration data could be described well by a one-compartment model, and concentrations in breast milk were linked to this model using an estimated milk-to-plasma concentration ratio (MPRcon). Significant variables that influenced drug exposure and MPRcon were identified as total bilirubin levels (TBIL) and postnatal sampling time, respectively. Simulations showed that women with abnormal liver function (TBIL > 17 μmol/L) had higher ornidazole levels in plasma and milk than those with normal liver function (TBIL < 17 μmol/L), but the exposures through colostrum of lactating women from both groups were below the safety threshold. This work provides a simple and feasible strategy for the prediction of drug exposure in breast milk and the assessment of breastfeeding safety.

Proteomic analysis of metronidazole resistance in the human facultative pathogen Bacteroides fragilis.

The anaerobic gut bacteria and opportunistic pathogen Bacteroides fragilis can cause life-threatening infections when leaving its niche and reaching body sites outside of the gut. The antimicrobial metronidazole is a mainstay in the treatment of anaerobic infections and also highly effective against Bacteroides spp. Although resistance rates have remained low in general, metronidazole resistance does occur in B. fragilis and can favor fatal disease outcomes. Most metronidazole-resistant Bacteroides isolates harbor nim genes, commonly believed to encode for nitroreductases which deactivate metronidazole. Recent research, however, suggests that the mode of resistance mediated by Nim proteins might be more complex than anticipated because they affect the cellular metabolism, e.g., by increasing the activity of pyruvate:ferredoxin oxidoreductase (PFOR). Moreover, although nim genes confer only low-level metronidazole resistance to Bacteroides, high-level resistance can be much easier induced in the laboratory in the presence of a nim gene than without. Due to these observations, we hypothesized that nim genes might induce changes in the B. fragilis proteome and performed comparative mass-spectrometric analyses with B. fragilis 638R, either with or without the nimA gene. Further, we compared protein expression profiles in both strains after induction of high-level metronidazole resistance. Interestingly, only few proteins were repeatedly found to be differentially expressed in strain 638R with the nimA gene, one of them being the flavodiiron protein FprA, an enzyme involved in oxygen scavenging. After induction of metronidazole resistance, a far higher number of proteins were found to be differentially expressed in 638R without nimA than in 638R with nimA. In the former, factors for the import of hemin were strongly downregulated, indicating impaired iron import, whereas in the latter, the observed changes were not only less numerous but also less specific. Both resistant strains, however, displayed a reduced capability of scavenging oxygen. Susceptibility to metronidazole could be widely restored in resistant 638R without nimA by supplementing growth media with ferrous iron sulfate, but not so in resistant 638R with the nimA gene. Finally, based on the results of this study, we present a novel hypothetic model of metronidazole resistance and NimA function.

Use of Magnetic Nanoparticles to Isolate Anaerobic Bacteria

Objective: Anaerobic bacteria, which make up an important part of normal body flora, may lead to serious life-threatening infections. Since isolation and identification of anaerobic bacteria require time-consuming, sensitive, and difficult methods, they can only be performed in certain clinical laboratories. For this reason, diagnosis and treatment of anaerobic infections are delayed and drug resistance is observed due to empirical treatment. New methods that will enable the early identification of these bacteria will help reduce the duration of treatment and mortality rates due to anaerobic infections. Method: In this study, it is aimed to design magnetic nanoparticles attached to N-methyl-D-glucamine (Mag-NMDG) to catch anaerobic bacteria for rapid identification. Mag-NMDG nanoparticles were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), and vibrating sample magnetometer (VSM). Results: Mag-NMDG nanoparticles were applied to gram positive and gram negative anaerobic bacteria such as Actinomyces odontolyticus, Prevotella buccae, Veillonella parvula, Bifidobacterium dentium and Bacteroides fragilis isolated from culture media. The binding of bacteria to Mag-NMDG was determined by microscope images, McFarland values, and MALDI-TOF MS identification scores. Conclusion: As a result of this study, it was concluded that the Mag-NMDG nanoparticles could be used to isolate anaerobic bacteria directly from samples. Thus, it is foreseen that many time-consuming and troublesome steps in the isolation and identification stages can be eliminated.

Prevalence and susceptibility pattern of anaerobic bacteria isolated from wound swabs in Clinical Centre University of Sarajevo

Objectives: Anaerobic bacteria may cause numerous infections in different locations through human body. Those infections can be life-threatening with significant mortality. Wounds represent a suitable habitat for colonization of anaerobic bacteria. Their proliferation contributes to moist and warm environment, hypoxic and necrotic tissue.Methods:A retrospective study was conducted at the Clinical Centre University of Sarajevo from 2015-2017. The study involved wound swab samples, sampled from hospitalized patients. The anaerobic bacteria were isolated using standard procedures.Results: During the period from 01.01.2015. to 31.12.2017, 8386 samples were analyzed on anaerobic bacteria and 872 (10.4%) of specimen were positive. In 2015, 332 (15%) specimens were positive, while during 2016 and 2017, 244 (7,8%) and 296 (9.9%) respectively. Bacteroides spp. was the most common isolate during three year period: 2015-227 (55.5%); 2016-139 (48%); 2017-161 (42,5%). It was followed by Peptococcus spp.: 2015-70 (17.1%); 2016-40 (13.9%); 2017-66 (17.4%), Clostridium spp.: 2015 – 32 (7.8%); 2016-21 (7.3%); 2017- 35 (9.2%), Fusobacterium spp.: 2015 – 49 (11.9%); 2016-32 (11.1%); 2017- 45 (11.9%).VITEK 2 Compact has identified to the level of species 48 isolates which were in pure culture.The largest number of anaerobic bacteria were isolated from the samples received from the Abdominal surgery. The overview of antimicrobial sensitivity showed highest sensitivity to metronidazole (99,9%) and carbapenems (99,9%), respectively.Conclusions The most commonly isolated anaerobic bacteria was Bacteroides spp.Highest number of positive isolates was from abdominal surgery since intra-abdominal infections reflect the microflora of the resected organ. Metronidazole remains the antibiotic of choice in the treatment of anaerobic infections.

Metronidazole-induced Encephalopathy.

Metronidazole is commonly used in the treatment of anaerobic infections. While neuropathy is known to be associated with metronidazole, encephalopathy has been rarely reported. We herein present a case of metronidazole-induced encephalopathy presenting as frequent falls and slurred speech. Magnetic resonance imaging of the brain demonstrated T2/FLAIR hyperintensity in the dentate nuclei bilaterally. Soon after the discontinuation of metronidazole, dysarthria and dysmetria resolved. Metronidazole-induced encephalopathy should be considered in patients presenting with new neurologic symptoms after the initiation of metronidazole.

Oculogyric Crisis Due to Metronidazole Toxic Encephalopathy

Oculogyric crisis is an acute dystonia involving ocular muscles characterized by sustained conjugate upward or lateral deviation of the eyes. Metronidazole is a commonly used antimicrobial agent in treatment of anaerobic infections. However, its long-term use can cause toxic encephalopathy particularly in patients with hepatic dysfunction. Here, we describe a case of oculogyric crisis as a presenting manifestation of metronidazole-induced encephalopathy. Key Words: Metronidazole, Encephalopathy, Dystonia

A review on metronidazole: an old warhorse in antimicrobial chemotherapy.

The 5-nitroimidazole drug metronidazole has remained the drug of choice in the treatment of anaerobic infections, parasitic as well as bacterial, ever since its development in 1959. In contrast to most other antimicrobials, it has a pleiotropic mode of action and reacts with a large number of molecules. Importantly, metronidazole, which is strictly speaking a prodrug, needs to be reduced at its nitro group in order to become toxic. Reduction of metronidazole, however, only takes place under very low concentrations of oxygen, explaining why metronidazole is exclusively toxic to microaerophilic and anaerobic microorganisms. In general, resistance rates amongst the pathogens treated with metronidazole have remained low until the present day. Nevertheless, metronidazole resistance does occur, and for the treatment of some pathogens, especially Helicobacter pylori, metronidazole has become almost useless in some parts of the world. This review will give an account on the current status of research on metronidazole's mode of action, metronidazole resistance in eukaryotes and prokaryotes, and on other 5-nitroimidazoles in use.

Spectrum and treatment of anaerobic infections.

Anaerobes are the most predominant components of the normal human skin and mucous membranes bacterial flora, and are a frequent cause of endogenous bacterial infections. Anaerobic infections can occur in all body locations: the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin, and soft tissues. Treatment of anaerobic infection is complicated by their slow growth in culture, by their polymicrobial nature and by their growing resistance to antimicrobials. Antimicrobial therapy is frequently the only form of therapy needed, whereas in others it is an important adjunct to drainage and surgery. Because anaerobes generally are isolated mixed with aerobes, the antimicrobial chosen should provide for adequate coverage of both. The most effective antimicrobials against anaerobes are: metronidazole, the carbapenems (imipenem, meropenem, doripenem, ertapenem), chloramphenicol, the combinations of a penicillin and a beta-lactamase inhibitors (ampicillin or ticarcillin plus clavulanate, amoxicillin plus sulbactam, piperacillin plus tazobactam), tigecycline, cefoxitin and clindamycin.

Antimicrobial treatment of anaerobic infections

Introduction: Anaerobes are the most predominant components of normal human skin and mucous membrane bacterial flora and are, therefore, a common cause of endogenous bacterial infections. Because of their fastidious nature, they are difficult to isolate from infectious sites and are often overlooked. Anaerobic infections can occur at all body sites, including the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin and soft tissues.Areas covered: This up-to-date review describes the antimicrobials available for the treatment of anaerobic infections and the advantages in using them according to the site of infection and expected antimicrobial susceptibility.Expert opinion: Treatment of anaerobic infection is complicated by the slow growth of these organisms, their polymicrobial nature and the growing resistance of anaerobes to antimicrobials. Antimicrobial therapy is often the only therapy required, or it is an important adjunct to a surgical approach. Because anaerobes generally are recovered mixed with aerobic organisms, the choice of appropriate antimicrobial should provide adequate coverage of both types of pathogen. The most effective antimicrobials against anaerobes are: metronidazole, the carbapenems, chloramphenicol, the combinations of a penicillin and a beta-lactamase inhibitor, and tigecycline.

Committee on guidelines for diagnosis and treatment of anaerobic infections

Committee on guidelines for diagnosis and treatment of anaerobic infections

Guidelines for diagnosis and treatment of anaerobic infections

Guidelines for diagnosis and treatment of anaerobic infections

Guidelines for diagnosis and treatment of anaerobic infections

Guidelines for diagnosis and treatment of anaerobic infections

Review of the in vitro activity and potential clinical efficacy of levofloxacin in the treatment of anaerobic infections

The activity of levofloxacin against aerobic bacteria has been well documented both in vitro and clinically, but its anaerobic activity has been infrequently studied. This new fluoroquinolone exhibits good in vitro activity (MIC S ⩽2.0 μg/mL) against many anaerobic pathogens associated with acute sinusitis, bite wounds, and other soft-tissue infections. It is less active against Bacteroides fragilis ( MIC 90 =2–4 μg/mL ) and has poor inhibitory activity against non- fragilis B. fragilis group species that are associated with gastrointestinal and genitourinary tract infections. Levofloxacin does not antagonize the in vitro activity of clindamycin and metronidazole and often provides additive or synergistic activity against anaerobic bacteria with these agents. In pharmacodynamic models, levofloxacin exhibits rapid bactericidal activity at 2–4 times the MIC of anaerobic bacteria. Prolonged killing is observed when the area-under-the concentration-time-curve to MIC ratio is greater than 40. In clinical efficacy trials, levofloxacin has been effective in the treatment of patients with gynecologic, skin and skin-structure, and bone infections involving anaerobic pathogens. Both micro-biologic and pharmacodynamic studies support further evaluations of levofloxacin in the treatment of selective mixed aerobic/anaerobic infections.

Comparative In Vitro Activity of PH-027 Versus Linezolid and Other Anti-Anaerobic Antimicrobials Against Clinical Isolates of Clostridium difficile and Other Anaerobic Bacteria

PH-027 is a new 5-triazole oxazolidinone synthesized in our laboratories, which shows strong activity against Gram-positive aerobic bacteria including clinical isolates. The objective of this study was to investigate the In Vitro activity of this compound in comparison with linezolid and other antibiotics against Gram-positive and Gram-negative anaerobes. The In Vitro activity of PH-027 in comparison with those of linezolid and other antimicrobial agents was evaluated against 201 clinical isolates of Gram-positive and Gram-negative anaerobic bacteria by agar dilution and Etest methods.PH-027 showed excellent activity, with minimum inhibitory concentrations (MIC) in the range of 0.12-4.0 μg/ml against all isolates; MIC90s being 4.0, 1.0, 2.0, 2.0 and 2.0 μg/ml against Clostridium difficile, Peptostreptococcus spp., Bacteroides fragilis, Prevotella bivia and Fusobacterium spp. respectively. In comparison, linezolid had MIC in the range of 0.5-4.0 μg/ml against all isolates, with MIC90s of 2.0, 4.0, 4.0, 4.0 and 2.0 μg/ml against the same set of bacteria respectively. PH-027 demonstrated excellent In Vitro activity that is superior to linezolid against Peptostreptococcus spp., B. fragilis and P. bivia. However, against C. difficile and Fusobacterium spp, PH-027 and linezolid showed comparable In Vitro activity. Against all anaerobes, metronidazole, PH-027 and, to a lesser extent, linezolid had the most potent activity. From the results of In Vitro susceptibility testing, both linezolid and PH-027 show promise in the treatment of anaerobic infections.

Metropol: a New Prolonged-Release Drug for the Treatment of Anaerobic Infections

Metropol: a New Prolonged-Release Drug for the Treatment of Anaerobic Infections

Clindamycin, Metronidazole, and Chloramphenicol

Clindamycin, metronidazole, and chloramphenicol are three antimicrobial agents useful in the treatment of anaerobic infections. Clindamycin is effective in the treatment of most infections involving anaerobes and gram-positive cocci, but emerging resistance has become a problem in some clinical settings. Metronidazole is effective in the treatment of infections involving gram-negative anaerobes, but it is unreliable in the treatment of gram-positive anaerobic infections and is ineffective in treating aerobic infections. Additionally, metronidazole is often the drug of choice in treating infections in which Bacteroides fragilis is a serious concern. Chloramphenicol is effective in the treatment of a wide variety of bacterial infections, including serious anaerobic infections, but is rarely used in Western countries because of concerns about toxicity, including aplastic anemia and gray baby syndrome.

Failure of intravenous antibiotic therapy of multiple temporal brain abscesses due to Propionibacterium acnes requiring temporal lobectomy

Propionibacterium acnes is a common skin colonizer. Its involvement in brain abscesses is generally described as a complication of neurosurgical intervention. Propionibacterium acnes is susceptible to antibiotics used as treatment of anaerobic infections, except for the 5-nitroimidazoles. Surgical excision or drainage of a simple abscess combined with a long course of antibiotics is considered the treatment of choice. A case of a patient with multiple brain abscesses located in the right temporal lobe that occurred after the manipulation of an abscess of the right upper maxillary is reported. The patient did not improve despite a prolonged course of high-dose intravenous penicillin plus thiamphenicol and cure was finally obtained after the excision of the right temporal lobe. Culture of the purulent material and the shell of the abscesses yielded P. acnes which was sensitive to all the antibiotics administered to the patient up to the intervention. The temporal lobectomy was followed by a 6-month course of ofloxacin. One year after the intervention, the patient remained apyretic without any other abscess on cranial computed tomography scan.

Possible role for the new fluoroquinolones (levofloxacin, grepafloxacin, trovafloxacin, clinafloxacin, sparfloxacin, and DU-6859a) in the treatment of anaerobic infections: review of current information on efficacy and safety.

The currently available fluoroquinolones have modest activity against anaerobes. Newer fluoroquinolones with increased in vitro activity against anaerobes are under development and include levofloxacin, clinafloxacin, sparfloxacin, trovafloxacin, grepafloxacin, and DU-6859a. Side effects of the quinolones have varied according to the specific compounds and include central nervous system stimulation, gastrointestinal disturbances, vasculitis, and photosensitization. Monitoring for toxicity is incompletely reliable in identifying all potential serious side effects such as the "temafloxacin syndrome." Other fluoroquinolones may produce this syndrome rarely or not at all. In this paper, I review limited published studies on the use of these agents for skin and skin-structure infections and gynecologic infections. Studies in progress are noted, and when available, in vitro data on the efficacy of these agents against bacterial isolates from specific sources are reviewed and evaluated in terms of potential clinical utility.

Nonsurgical treatment of patients with periodontal disease

Objectives To determine whether the short-term use of systemic antimicrobials (metronidazole or doxycycline) and locally delivered antimicrobials (metronidazole, chlorhexidine) in patients with advanced forms of perodontal disease could prevent the normally necessary access surgery. Study designs Ninety-four patients were randomly assigned with the use of a double-blind protocol. Results There was a 93% reduction in the need for periodontal surgery about individual teeth and an 81% reduction in the need for tooth extractions. Only 93 teeth of an initial total of 783 teeth actually needed surgery or extractions. Eighty-one percent of the patients entered into the maintenance phase of treatment without needing surgical treatments. Conclusions These findings indicate that a treatment paradigm based on the diagnosis and treatment of anaerobic infections is likely to be successful in those patients for whom access surgery is recommended.

Antibiotic treatment of anaerobic infections.

The discovery of effective antimicrobial drugs has substantially improved the therapeutic outlook for patients with anaerobic infections. In addition, the pathophysiology of anaerobic infections has been elucidated by comparative antibiotic trials and the use of antibiotic probes in experimental animal models. Facultative bacteria, such as Escherichia coli, are responsible for acute peritonitis and sepsis associated with bowel perforation. Anaerobes, particularly Bacteroides fragilis, play the seminal role in subsequent abscess formation. Treatment of only the facultative bacteria, without adequate antibiotic coverage for anaerobic bacteria, leads to clinical failures with complications of abscess formation. Such therapeutic misadventures have been witnessed in the treatment of mixed infections with cephalosporins and penicillins that lack significant activity against anaerobes. Similarly, use of metronidazole or clindamycin as a single agent is associated with failures caused by infection with facultative bacteria. Mixed infections involve complex interactions between facultative bacteria and strict anaerobes, many of which possess intrinsic pathogenicity. The best therapeutic results are realized with antimicrobial drugs that are active against both types of microorganisms.