Cefpodoxime proxetil in patients with endstage renal failure on hemodialysis

Summary The blood levels of cefpodoxime of 16 hemodialysis patients were monitored after a single oral of Cefpodoxime proxetil with a Cefpodixime-equivalent of 200 mg dose. Eight patients were on dialysis during the period of observation, while the other eight patients were observed during a non-dialysis period. During hemodialysis the cefpodoxime levels were determined before and after the capillary dialyzer. It became apparent that hemodialysis patients have considerably higher and longer-lasting concentrations than patients with normal kidney function. The area under the curve is about seven times greater. Cefpodoxime is thus apparently eliminated to a great extent renally. The concentration levels before capillary dialyzer are noticeably higher than those after capillary dialyzer, so that it can be assumed that cefpodoxime is being dialyzed: the area under the curve of the eight patients observed during hemodialysis was about 50% less than that of the patients observed while not on hemodialysis. Based on the pharmacokinetic data gathered, simulations of the course of concentration were made which took into consideration the clinical circumstances (normal period of dosage administration and dialysis). According to these simulations one can recommend a loading dose of 200 mg and thereafter a dose of 100 mg 12 h later followed by 100 mg every 24 h. This will result in an average concentration of 2 mg/l and never falling below 1.5 mg/l. With this schedule all bacteria considered to be sensitive can be reached. Cefpodoxime proxetil thereby ensures a simple and effective therapy of bacterial infections in hemodialysis patients.

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Cefpodoximproxetil bei Patienten mit terminaler Niereninsuffizienz unter Hämodialyse

Zusammenfassung Nach oraler Gabe von Cefpodoximproxetil (Cefpodoxinäquivalent=200 mg) wurden die Plasmaspiegel von Cefpodoxim bei 16 Hämodialyse-Patienten verfolgt. Acht Patienten wurden während des Untersuchungszeitraumes dialysiert; bei der zweiten Gruppe fiel die Untersuchung in das dialysefreie Intervall. Während der Hämodialyse wurden die Cefpodoximproxetil-Konzentrationen vor und hinter der Capillarniere bestimmt. Es zeigte sich, daß Hämodialyse-Patienten höhere und insbesondere wesentlich länger anhaltende Spiegel aufweisen als Normalpersonen. Die Fläche unter der Plasmaspiegelkurve (AUC) liegt etwa um den Faktor 7 höher. Offenbar wird Cefpodoximproxetil in hohem Maße renal eliminiert. Die Spiegel vor der Capillarniere liegen deutlich höher als die hinter der Capillarniere, so daß geschlossen werden kann, daß Cefpodoximproxetil dialysiert wird: Die AUC der acht Patienten unter Hämodialyse lag um zirka 50% unter der der Patienten außerhalb der Hämodialyse. Aufgrund der gewonnenen pharmakokinetischen Daten wurden Simulationen der Plasmaspiegel vorgenommen, die klinische Gegebenheiten (übliche Applikations- und Dialysezeiten) berücksichtigen. Aufgrund dieser Simulationen wird empfohlen, nach einer Initialdosis von 200 mg 12 h später 100 mg und dann alle 24 h 100 mg als Erhaltungsdosis zu geben. Es werden so Spiegel erreicht, die minimal um 1,5 mg/l und im Mittel um 2 mg/l liegen. Hiermit dürften alle als sensibel bezeichneten Keime erfaßt werden. Cefpodoximproxetil erlaubt somit eine einfache und effektive Therapie von bakteriellen Infektionen bei Hämodialyse-Patienten.

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This article contains substantial results of the dissertation ofM. Corcilius.

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Dedicated to Prof. Dr.F. Scheler on the occasion of his 65th birthday.     

Significant correlation of matrix metalloproteinase and macrophage colony-stimulating factor serum concentrations in patients with head and neck cancer

Serum matrix metalloproteinases (MMPs) and the macrophage colony-stimulating factor (M-CSF) are of potential interest as serum tumor markers in various malignancies. There is still a lack of reliable tumor markers in patients with squamous cell carcinoma of the head and neck (SCCHN). Therefore, the tumor marker potential of MMPs and M-CSF was investigated in these malignancies. Serum of 59 patients suffering from SCCHN and of 59 healthy volunteers was obtained. The concentration of MMP-3, MMP-8, MMP-9, and M-CSF was determined by sandwich enzyme immunoassays. The MMP- 3, -8, -9, as well as the M-CSF serum concentrations were significantly elevated in the patient group, compared to the healthy controls (p<0.001, p<0.05, p<0.001, p=0.002). There was significant correlation between the M-CSF and the MMP-3 serum concentration (p<0.0001), and between the M-CSF and the MMP-8 serum concentration (p=0.005). A significant correlation with the tumor stage was found only for MMP-8. MMP and M-CSF serum concentrations are of potential interest as serum tumor markers in SCCHN.     

Mycetoma of the head and neck

Cranial mycetoma is not as rare as was believed. In the Sudan, the majority of cases are caused by S. somaliensis; no cases were found to be caused by Nocardia species. Cranial actinomycetoma proved to be potentially fatal and was the most difficult to treat. The best treatment results were achieved in cases of A. madurae infection.     

Stem cells in squamous head and neck cancer

The initiation and metastasis of head and neck squamous cell carcinomas (HNSCC) and other cancers have recently been related to the presence of cancer stem cells (CSC). CSC are cancer initiating, sustaining and are mostly quiescent. Specific markers that vary considerably depending on tumor type or tissue of origin characterize putative CSC. Compared to the bulk tumor mass, CSC are less sensitive to chemo- and radiotherapy and may also have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome of HNSCC which has two distinct etiologies: infection of epithelial stem cells by high-risk types of the human papillomavirus, or long-term tobacco and alcohol abuse. Recent knowledge on the role of CSC in HNSCC is reviewed and where necessary parallels to CSC of other origin are drawn to give a more comprehensive picture.     

Space infection of the head and neck

Deep neck infection may be lethal, especially when life-threatening complications occur. We conducted a retrospective analysis of 184 patients with deep neck infection who were treated at Kaohsiung Medical University Hospital during the past 6 years. Factors such as age, sex, hospitalization days, clinical presentations, involved spaces, imaging studies, microbiology, and treatment method were analyzed. There were 122 men and 62 women with a mean age of 41.7 years. The average hospitalization was 8.4 days. The involved spaces, determined by physical examination and radiologic findings, were the peritonsillar space (59 patients), parapharyngeal space (77 patients), submandibular space (55 patients), and retropharyngeal space (20 patients). Of the 49 patients for whom the origin of infection was identified, 29 were infected via the upper respiratory tract and 13 had infection of odontogenic origin. The most common isolated organism was Klebsiella pneumoniae. One hundred and thirty-seven patients (74.5%) underwent surgery, including repeated needle aspiration (87 patients) and surgical drainage (50 patients). The remaining 47 patients recovered uneventfully with antibiotic therapy alone. Eighteen patients developed life-threatening complications, such as descending mediastinitis, sepsis, airway obstruction, and jugular vein thrombosis. Two patients died of septic shock. The combination of accurate diagnosis, effective antibiotic therapy, airway maintenance, and intensive surgical debridement for those who fail to respond to conservative treatment will lead to a good prognosis.     

Mycobacterial infections of the head and neck

Mycobacteria are important causes of head and neck infections. Mycobacterial lymphadenitis may be caused by both Mycobacterium tuberculosis and a variety of nontuberculous myocbacteria. Changes in the epidemiology of tuberculosis have caused a shift of the peak age range of tuberculous lymphadenitis from childhood to ages 20 to 40 years. Short-course chemotherapy is highly effective. Mycobacterium avium has become the most common cause of nontuberculous lymphadenitis, but new mycobacterial species are increasingly recognized. Treatment consists primarily of complete surgical excision, although roles for antimycobacterial chemotherapy are being identified. Transient flares of mycobacterial lymphadenitis, which occur during initiation of antituberculous therapy and in HIV-infected patients after initiation of antiretroviral therapy, may respond to short courses of corticosteroids. Tuberculous otitis media has become uncommon. Otitis media due to nontuberculous mycobacterial infection is increasingly seen in patients with pre-existing ear disease and after surgical and otic interventions. Tuberculosis of the eye has also become uncommon but may occur via hematogenous dissemination or direct innoculation. Nontuberculous mycobacteria, most commonly Mycobacterium chelonae and Mycobacterium fortuitum, may cause keratitis, usually after some form of corneal trauma.     

Common head and neck manifestations of AIDS

Head and neck manifestations of acquired immunodeficiency syndrome (AIDS) can involve the skin, ear, upper aerodigestive tract, and neck. Several head and neck manifestations of AIDS may be the only initial sign of this disease process and therefore primary-care physicians and otolaryngologists must be able to recognize and understand the management of these lesions. Cystic enlargement of the parotid gland and Kaposi's sarcoma are increasingly being encountered in the head and neck exam of HIV-infected patients. An example of each of these disease processes is presented with full discussion about the various treatment methods.     

Anatomic basis of head and neck infections

The head is the portal for all infections acquired by ingestion and inhalation. The oropharynx, with its fine microbiologic niches around the teeth, serves as a source for endogenous pyogenic infections of the head and neck. The anatomic connections of the head with the mediastinum through extensions of the deep cervical fascia, and the intracranial venous sinuses connected through emissary veins to the facial veins, make infections of this region the most dreaded. Perhaps no other set of lymph nodes in the human body is challenged as frequently by microbiologic insults as the cervical lymph nodes.     

Laser therapy for head and neck tumors

Conclusion Lasers are important tools used in treating various tumors and other conditions of the upper aerodigestive tract. The choice of laser is dependent upon wavelength (having characteristic tissue effects) and the delivery system that permits best access to the target (Table 1). Hazards of laser use can be minimized by proper training and attention to technical details.     

Microbiologic investigations for head and neck infections

A variety of methods, including direct examination of stained smears, antigen detection, routine and special cultures, and histopathologic evaluation are available for investigation of head and neck infections. Newer rapid molecular techniques with increased sensitivity and specificity are becoming available at many centers. Evaluation of specific causes in head and neck infections is complicated by the tendency for polymicrobial infections, difficulty in obtaining adequate specimens, and the presence of a diverse endogenous microflora at various mucosal sites that also can include true pathogens. These aspects of laboratory investigation for head and neck infections are reviewed in this article.     

Imaging studies for head and neck infections

Imaging the head and neck presents a unique challenge because of the dense concentration of complex anatomy and the importance of lesion localization in formulating the differential diagnosis and prognosis. Critical imaging features such as the ability to define fascial borders of soft tissue neck compartments, the demonstration of intricate anatomy such as the temporal bones and paranasal sinuses, and the noninvasive assessment of vascular integrity have improved greatly in recent years in parallel with the rapid technologic advances in multidetector CT and MRI. After comparing the available imaging techniques, this article explores the imaging findings by anatomic region.     

Dysphagia following head and neck cancer surgery

Surgical resection of head and neck cancer results in predictable patterns of dysphagia and aspiration due to disruption of the anatomic structures of swallowing. Common procedures undertaken in the treatment of head and neck cancer include tracheostomy, glossectomy, mandibulectomy, surgery on the palate, total and partial laryngectomy, reconstruction of the pharynx and cervical esophagus, and surgery of the skull base. An overview is presented of normal swallowing physiology, as well as swallowing perturbations that are frequently encountered in postoperative head and neck cancer patients.     

Diagnostic approaches to head and neck infections

This article covers both the microbiologic techniques for diagnosis of head and neck infections and imaging techniques for localization of those infections. These approaches are used in a detailed discussion of specific infections of the head and neck regions.