This chapter looks at fever and rash, one of the common symptom complexes presenting in medical practice. Because of the wide range of diseases that can present with this complex, the patient presenting with fever and rash is also one of the most challenging. Rapid recognition and therapeutic intervention are essential in certain diseases presenting with fever and rash to minimize as much as possible the associated morbidity and mortality. The major conditions involved include meningococcemia, Rocky Mountain spotted fever, staphylococcal toxic shock syndrome, streptococcal toxic shock-like syndrome, bacteremia or endocarditis with septic emboli, and rapidly spreading cellulitis. All these conditions can present with fever and rash in a fulminant, rapidly progressive form requiring expedient therapeutic intervention, often on an empiric basis before confirmation of the diagnosis if the associated mortality rates are to be minimized.

Mycoplasma pneumoniae continues to be the most frequent cause of atypical pneumonia. Fortunately, the antibiotics listed in this article are generally very effective. Major skills are needed to detect M pneumoniae extrapulmonary diseases, which require a special heightened awareness and sensitivity. It is not known whether early therapy prevents dreaded complications.

Fever of unknown origin (FUO) refers to disorders that present with prolonged and perplexing fevers that are difficult to diagnose. This article presents a clinical overview of classic and current causes of FUOs, which may be due to infectious, rheumatic/inflammatory, neoplastic, or miscellaneous disorders. Comprehensive but nonfocused diagnostic testing is ineffective and should be avoided. The FUO workup should be directed by the key history, physical, and laboratory findings in clinical presentation. The clinical syndromic approach in the differential diagnosis of FUOs is emphasized, and the diagnostic importance and significance of fever patterns are discussed.

ABSTRACT Linezolid, an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens including multidrug-resistant staphylococci, enterococci, and pneumococci. Safety assessments were conducted for 2,046 linezolid-treated patients and 2,001 comparator drug-treated patients from seven controlled clinical trials comparing the activities of linezolid and comparator drugs against nosocomial and community-acquired pneumonia, skin and skin structure infections, and methicillin-resistant staphylococcal infections. Drug-related adverse events were primarily transient. The most frequent (≥2%) adverse events caused by linezolid and the comparator drugs were diarrhea (4.3 and 3.2%, respectively; P = 0.074), nausea (3.4 and 2.3%, respectively; P = 0.036), and headache (2.2 and 1.3%, respectively; P = 0.047). Treatment discontinuations due to drug-related events (2.4 and 1.9%, respectively), serious adverse events (11.4 and 10.6%, respectively), and deaths (4.8 and 4.9%, respectively) were similar. No clinically significant drug-related hematologic events were reported, and laboratory safety data were comparable. In the first 6 months of postmarketing surveillance, hematologic abnormalities were reported in 0.1% of linezolid-treated patients, but no irreversible blood dyscrasias were documented. The risk for transient, reversible hematologic effects from treatment with linezolid should be considered together with the clinical benefits associated with its use.

Hyposplenism, secondary to splenectomy or disease state, predisposes the host to overwhelming infection with certain bacteria, such as S. pneumoniae. Recognition of the hyposplenic state and preventive measures, including patient education and vaccination, appear to reduce the rate of this highly fatal infection. In addition to considering chemoprophylaxis, a clinician should promptly evaluate or empirically treat all febrile episodes in hyposplenic patients.

The use of antimicrobial agents (i.e., penicillins, cephalosporins, macrolides, aminoglycosides, tetracyclines, quinolones) have continued to grow at an astounding rate. Centers for Disease Control and Prevention estimates are of some 150 million prescriptions annually in the United States, amounting to some 50 millions pounds of antibiotics annually being used in the United States with some 15 to 17 million pounds being used in livestock and agriculture alone. These large numbers serve as indicators for caution and concern. Most oral antibiotics are prescribed for respiratory tract infections, more than half of which are probably viral, for which antimicrobials are not necessary. This overprescribing is noted at a time when increasing antimicrobial resistance is being recognized in hospital settings as well as in the community. The dilemma for the practitioner is to be able to use antibiotics efficaciously and prevent overusage and overprescribing.

ABSTRACT This randomized, double-blind, multicenter trial compared the efficacy and safety of linezolid, an oxazolidinone, with those of oxacillin-dicloxacillin in patients with complicated skin and soft tissue infections. A total of 826 hospitalized adult patients were randomized to receive linezolid (600 mg intravenously [i.v.]) every 12 h or oxacillin (2 g i.v.) every 6 h; following sufficient clinical improvement, patients were switched to the respective oral agents (linezolid [600 mg orally] every 12 h or dicloxacillin [500 mg orally] every 6 hours). Primary efficacy variables were clinical cure rates in both the intent-to-treat (ITT) population and clinically evaluable (CE) patients and microbiological success rate in microbiologically evaluable (ME) patients. Safety and tolerability were evaluated in the ITT population. Demographics and baseline characteristics were similar across treatment groups in the 819 ITT patients. In the ITT population, the clinical cure rates were 69.8 and 64.9% in the linezolid and oxacillin-dicloxacillin groups, respectively (P = 0.141; 95% confidence interval −1.58 to 11.25). In 298 CE linezolid-treated patients, the clinical cure rate was 88.6%, compared with a cure rate of 85.8% in 302 CE patients who received oxacillin-dicloxacillin. In 143 ME linezolid-treated patients, the microbiological success rate was 88.1%, compared with a success rate of 86.1% in 151 ME patients who received oxacillin-dicloxacillin. Both agents were well tolerated; most adverse events were of mild-to-moderate intensity. No serious drug-related adverse events were reported in the linezolid group. These data support the use of linezolid for the treatment of adults with complicated skin and soft tissue infections.

A double-blind, placebo-controlled trial of efficacy and safety of thalidomide in AIDS-associated wasting was carried out. Ninety-nine of 103 male patients had at least one on-study measurement (intent-to-treat [ITT] cohort). Patients were randomized to thalidomide at 100 mg/day (T100) or 200 mg/day (T200), or placebo for 8 weeks. By ITT analysis, the mean change in body weight of the placebo, T100, and T200 treatment groups was 0.3 kg (0.4%), 2.0 kg (3.0%), and 0.9 kg (1.4%), respectively (p = 0.021 for T100 versus placebo; p = 0.53 for T200 versus placebo). Of the 64 patients who completed the 8 weeks of study treatment, significant weight gain was observed in both the T100 group (2.2 kg, [33%]; p = 0.008 versus placebo) and the T200 group (1.5 kg [2.5%]; p = 0.019 versus placebo). Approximately half the weight gain was fat-free mass (bioimpedance analysis). Patients in the T100 or T200 groups had no significant change in CD4+ cell counts, neutrophil counts, or TNF-alpha levels, compared with placebo. HIV viral load measured as log10 copies/ml decreased by a median of 0.07 in the placebo group, and increased by a median of 0.29 (T100 group) and 0.23 (T200 group) (p = 0.024 andp = 0.018 versus placebo, respectively). Thalidomide therapy was associated with mild to moderate rashes and fevers, but not peripheral neuropathy. Although the anabolic benefits of high-dose thalidomide are limited by drug intolerance, 8 weeks of low-dose thalidomide results in significant weight gain in patients with AIDS-associated wasting.

Most hematologic malignancies are rare during the childbearing years with the exception of Hodgkin's lymphoma. However, the continued spread of retroviruses, such as human immunodeficiency virus, in the heterosexual population may result in a substantial rise in viral-induced non-Hodgkin's lymphomas. Although pregnancy does not affect the natural course of these illnesses, adequate staging and therapy can be a difficult task. The obstetrician and the consultant hematologist/oncologist must weigh the benefit of immediate treatment while minimizing toxicity to the fetus.

Pneumocystis carinii pneumonia carries a high morbidity and mortality. Prophylaxis has proved to have a significant impact on survival and quality of life in patients infected with the HIV virus. The economic impact of prophylaxis is well recognized. Every effort should be directed at early institution of Pneumocystis carinii pneumonia prophylaxis. It is the standard of care to employ one of the acceptable means of prophylaxis discussed in this review.

We report the magnetic resonance imaging (MRI) findings in a unilocular multicystic adult granulosa cell tumor of the ovary. MRI, in conjunction with the clinical and laboratory findings, helped establish a preoperative diagnosis.

The opportunistic infections (01) and malignancies that characterize the acquired immune deficiency syndrome (AIDS) am now well-known and have been reflected in the Centers for Disease Control (CDC) AIDS surveillance definition since 1985. They reflect a state of cellular immune deficiency brought about by the HIVinduced depletion of helper T-lymphocytes. Development and widespread use of screening tests for antibodies to HIV has facilitated study of the natural history of HIV infection and allowed identification of conditions associated with HIV infection other than 01 or malignancy. Organ dysfunction due to HIV itself was first widely recognized in the nervous system with peripheral neuropathy and dementia. More recently, HIV infection in the absence of other 01 has been linked with dysfunction of other organs. These will be discussed below along with some of the recently recognized infectious problems occurring in patients infected with HIV.

Ticarcillin, a broad-spectrum penicillin [l], is susceptible in inactivation by a number of beta-lactamases. Clavulanic acid, a naturally occurring beta-lactamase inhibitor, has been shown to prevent the enzymatic degradation of beta-lactam antibiotics by a number of bacterial species [2]. In vitro studies have shown that in combination, ticarcillin and clavulanic acid may be synergistic in activity [3,4]. In the current study, we evaluated the clinical efficacy and safety of this combination in hospitalized patients with skin and skin structure infections. PATIENTS AND METHODS Patient Population. This research protocol was approved by the Human Studies Committee at both Hahnemann University Hospital and St. Michael’s Medical Center. The 79 patients in this study were adults hospitalized at either of the just mentioned medical centers, and informed consent was obtained by the investigators from each patient who entered the study. Each patient had either an acute or chronic skin or skin structure infection caused by an organism or organisms known or suspected to be susceptible to the combination of ticarcillin plus clavulanic acid. Patients excluded from the study included: pregnant or lactating women; recipients of an antimicrobial agent within the previous 72 hours to which the pathogen was susceptible; subjects with a known hypersensitivity to penicillin; and patients with known moderate to severe renal or hepatic dysfunction. Laboratory Studies. The following laboratory determinations were made before, during, and after treatment with ticarcillin plus clavulanic acid: complete hemogram, prothrombin time, quantitative platelet count, direct Coombs’ test, alkaline phosphatase, bilirubin, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, lactic dehydrogenase, serum concentrations of sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, serum creatinine, blood glucose, and urinalysis. Blood, purulent exudates from wounds, pus from abscesses, and excised tissue were obtained before, during, and after antibiotic therapy for aero

Patients who had prior anti-tuberculosis medications for pulmonary tuberculosis and who return to the hospital with culture-positive tuberculosis have been considered to be at risk of harboring resistant bacilli (secondary resistance or acquired resistance). The present recommendation for therapy of these patients is to resume earlier anti-tuberculosis medications and to add two new agents until the drug susceptibilities of the bacilli are known. This study reviewed 112 cases of readmissions for active tuberculosis and evaluated the risk of acquired drug resistance in this group. Patients with 6 months or less of prior therapy rarely harbored resistant organisms. Patients with 6–12 months of prior therapy had an 88% possibility of harboring resistant bacilli, but only a 30% risk of harboring multiple-drug resistant bacilli. Patients with 12 months or more of prior therapy had a 66% risk of harboring multiple-drug resistant, difficult-to-treat bacilli. This data would indicate that only those patients who have had prior therapy for 7 months or more require aggressive initial readmission therapy with 4 or more anti-tuberculosis agents. Hopefully this finding will not only help clinicians to identify readmission tuberculosis patients who are at increased risk of harboring resistant organisms but will also help them to be more selective in prescribing aggressive, potentially toxic, multiple-drug regimens.

The successful surgical treatment of multiple brain abscesses by means of needle aspiration is reported. There is a need for aggressive surgical and antibiotic treatment, using local anesthesia and needle aspiration, when fully developed abscesses are present. The computerized tomographic scan and related surgical techniques allow for a precise localization of an abscess and its evacuation even if it is located in so-called vital areas of the brain.

To the Editor.—St Michael's Medical Center was one of the first medical training schools to offer an individualized program to part-time interns and residents. Part-time residencies have been offered to practicing physicians, married women, researchers, and physicians with large debts. Because of the growing cost of medical education and the depletion of funds to pay house officers by third-party payers, we have had a great interest in the part-time program lately. This program has been particularly appealing to those with large financial responsibilities who are seeking highly specialized fellowships or miniresidencies in special skills. It has also attracted physicians who wish to transfer from one specialty to another. In all, seven house officers have participated in St Michael's program: five men and two women physicians. The programs were arranged to meet their individual needs. One American-trained woman, for example, did her internship over a three-year period during a time