Natalie C. Klein

Infections associated with steroid use.

Patients receiving chronic steroids have an increased susceptibility to many different types of infections. The risk of infection is related to the dose of steroid and the duration of therapy. Although pyogenic bacteria are the most common pathogens, chronic steroid use increases the risk of infection with intracellular pathogens such as Listeria, many fungi, the herpes viruses, and certain parasites. Clinicians should consider both common and unusual opportunistic infections in patients receiving chronic steroids.

Third generation cephalosporins.

Third-generation cephalosporins are broad-spectrum antimicrobial agents useful in a variety of clinical situations. No one cephalosporin is appropriate for all infectious disease problems. Cefotaxime and ceftizoxime have the best gram-positive coverage of the third-generation agents. Ceftazidime and cefoperazone are the only third-generation drugs that provide antipseudomonal coverage. Ceftriaxones long half-life allows for once-daily dosing, making ceftriaxone an excellent drug for outpatient antibiotic therapy of community-acquired infections. Ceftriaxone is also useful for the treatment of Lyme disease and sexually transmitted diseases. The third-generation cephalosporins except for cefoperazone penetrate cerebrospinal fluid and are indicated for the treatment of bacterial meningitis. Their proven record of clinical efficacy, favorable pharmacokinetics, and low frequency of adverse effects make third-generation cephalosporins the preferred antibiotic in many clinical situations.

TREATMENT OF FEVER

Fever is an important indicator of disease and should not be routinely suppressed by antipyretics. There is considerable evidence that fever may actually benefit the host defense mechanism. In most patients, fever is short-lived and causes only minor discomfort. Antipyretic agents are effective in lowering temperature, but have significant side effects. Routine antipyretic therapy should be avoided but may be necessary in individual patients with underlying cardiovascular or neurologic disorders.

NEW USES OF OLDER ANTIBIOTICS

Despite the development of extended-spectrum penicillins, cephalosporins, and quinolones, the older antimicrobial agents, doxycycline, minocycline, TMP-SMX, clindamycin, and metronidazole, still play an important role in the treatment of infectious diseases. All of these older drugs are well absorbed by the oral route, attaining serum levels equivalent to those achieved by parenteral administration. The availability of generic forms of the older drugs reduces their cost. Besides traditional uses, some older drugs have become the preferred therapy for newly recognized infectious diseases. Doxycycline is the preferred drug for rickettsial tickborne diseases, ehrlichiosis and early Lyme disease. TMP-SMX is the preferred drug for I. belli and Cyclospora. Minocycline has been used to treat MRSA and MRSE infections. Clindamycin or metronidazole combined with a quinolone is an excellent oral regimen for polymicrobial infections. [table: see text]

Profound and Prolonged Lymphocytopenia with West Nile Encephalitis

Infectious Common HIV/AIDS Typhoid fever Babesiosis Malaria Uncommon Viral hepatitis Tuberculosis Histoplasmosis Brucellosis Noninfectious Common Sarcoidosis Chronic corticosteroid use Antilymphocyte globulin Cancer chemotherapy Radiation therapy Rheumatoid arthritis Systemic lupus erythematosus Hodgkin’s disease Chronic alcohol abuse Uncommon CD4 lymphocytopenia Severe combined immunodeficiency Ataxia telangiectasia Wiskott-Aldridge syndrome Thoracic duct drainage Myasthenia gravis Idiopathic Profound and Prolonged Lymphocytopenia with West Nile Encephalitis

Fatal case of pneumonia associated with pandemic (H1N1) 2009 in HIV-positive patient.

To the Editor: Pandemic (H1N1) 2009 virus first appeared in March 2009 in Mexico. In June 2009, a pandemic was declared by the World Health Organization (1). Influenza A virus (H1N1) caused a pandemic in 1918–1919; estimated deaths were ≈100 million worldwide (2). Symptoms of pandemic (H1N1) 2009 are similar to those of seasonal influenza (fever, cough, sore throat, body aches, headache, chills, and fatigue) (3). Pandemic (H1N1) 2009 should be considered in the differential diagnosis of patients with acute febrile respiratory illness who have been in contact with persons with confirmed influenza or reside in areas where influenza has been reported (2). Although most cases of pandemic (H1N1) 2009 in the United States have been mild, 2%–5% of infected persons have required hospitalization (2). Immunosuppressed persons, the elderly, persons with underlying lung or cardiac disease, pregnant women, persons with diabetes, obese persons, and children <5 years of age are at increased risk for this disease (4). We report pneumonia associated with pandemic (H1N1) 2009, which resulted in respiratory and renal failure and death, in a 39-year-old HIV-positive woman. She had type 1 diabetes and a diagnosis of AIDS 7 years ago and had received highly active antiretroviral therapy. She also had an ill child at home with an influenza-like illness. Her medical history included pleuropericardial Nocardia spp. infection, recurrent pleural effusions requiring thoracentesis, and hepatomegaly of unknown cause. Her most recent CD4 cell count was 166 cells/μL with undetectable viral load 1 month before admission. Medications prescribed included combivir, efavirenz, and trimethoprim/sulfamethoxazole but she was noncompliant. She had received the 2008–09 seasonal influenza vaccine and pneumococcal vaccine. The patient was admitted to Winthrop-University Hospital (Mineola, NY, USA) on June 5, 2009, for community-acquired pneumonia. She received empiric moxifloxacin and atovaquone. Because of concern for persistent Nocardia spp. infection, she was also treated with doxycycline. The result of a rapid influenza test (QuickVue; Quidel, San Diego, CA, USA) was negative for a nasal swab specimen on day 1 of hospitalization. Over the next 48 hours, her clinical status deteriorated, and she experienced worsening hypotension and respiratory distress. On admission, she had fever (101°F) for 3 days, pulse rate of 109 beats/min, blood pressure of 86/52 mm Hg, respiratory rate of 22 breaths/min (oxygen saturation of 88% on room air), generalized weakness, nonproductive cough, and increasing shortness of breath. She was alert and oriented. Physical examination showed decreased breath sounds at bases, hepatomegaly, and bilateral edema in the lower extremities. Laboratory tests showed 3,000 leukocytes/mm3 (93% neutrophils, 2% bands, and 3% lymphocytes), hemoglobin level of 12.7 g/dL, and 118,000 platelets/mm3. Other laboratory values were blood urea nitrogen 66 mg/dL, creatinine 2.9 mg/dL, creatinine phosphokinase 2,276 IU/L, and lactic acid 3.6 mmol/L (anion gap 13). A chest radiograph showed moderate pleural effusion in the right lung and retrocardiac air space disease. Test results for influenza virus, respiratory fluorescent antibodies (D3 Ultra DFA Respiratory Virus Screening and Infectious Disease Kit; Diagnostic Hybrids, Inc., Athens, OH, USA), and virus culture were negative. The patient was transferred to the intensive care unit and required intubation, pressor support, and continuous venovenous hemofiltration for fluid removal. Empiric oseltamivir (150 mg 2×/d) was started on hospital day 3; moxifloxicin was discontinued, and meropenem was given for pneumonia (5). Thoracentesis showed transudative fluid negative for acid-fast bacilli, bacteria, and fungi. Results of blood cultures and urine analysis for Legionella spp. antigen were negative. Repeat chest radiography showed a right-sided pneumothorax and worsening bilateral airspace disease. A chest tube was inserted in the right lung, and bronchoscopy was performed on hospital day 5. Results of bronchoalveolar lavage were negative for Pneumocystis jiroveci, virus inclusions, fungi, acid-fast bacilli, bacteria, and mycobacteria. However, clusters of filamentous organisms were seen. On hospital day 5, results of a second rapid influenza test, respiratory fluorescent antibody test, and nasopharyngeal virus culture were negative. Diagnosis was based on a positive result for pandemic (H1N1) 2009 by real-time reverse transcription–PCR (RT-PCR) for a nasopharyngeal swab specimen (New York State Department of Health). Despite empiric treatment with oseltamivir, the patient died on June 15, 2009 (day 11 of hospitalization). Symptoms of pandemic (H1N1) 2009 in HIV-infected persons are not known. However, these persons have a higher risk for complications. In previous seasonal influenza outbreaks, HIV-infected persons had more severe infections and increased hospitalization and mortality rates (6). Although a diagnosis of pandemic (H1N1) 2009 was first considered for our patient because of her ill child, she was not initially treated with oseltamivir because of the negative influenza test result and concern for opportunistic infections. Only the result of an RT-PCR for pandemic (H1N1) 2009 was positive. No other pathogens were detected in her blood, urine, sputum, bronchoalveolar lavage, or thoracenthesis fluid. Empiric treatment in patients with pandemic (H1N1) 2009 should be considered in those seeking treatment for influenza-like symptoms, especially in the setting of sick contacts with respiratory illnesses. Rapid influenza tests, respiratory fluorescent antibody tests, and viral cultures may not provide a diagnosis. An RT-PCR for pandemic (H1N1) 2009 may be needed to provide a diagnosis.

Varicella-zoster virus meningoencephalitis in an immunocompetent patient without a rash

Abstract Varicella-zoster virus (VZV) is an unusual cause of meningoencephalitis in the immunocompetent patient. Most cases of VZV-associated aseptic meningitis or encephalitis are associated with the skin rash of primary varicella, localized herpes zoster, or disseminated zoster. We report a case of VZV meningoencephalitis without a rash occurring in a normal host.

Klebsiella pneumoniae pneumonia

Klebsiella pneumoniae is an uncommon cause of community-acquired pneumonia except in alcoholics. Klebsiella may mimic pulmonary reactivation tuberculosis because it presents with hemoptysis and cavitating lesions. Klebsiella pneumoniae is a difficult infection to treat because of the organisms thick capsule. Klebsiella is best treated with third- and fourth-generation cephalosporins, quinolones, or carbapenems. Monotherapy is just as effective as a combination treatment in Klebsiella pneumoniae because newer agents are used. In the past, older agents with less anti-Klebsiella activity were needed for effective treatment. The patient we present was initially thought to have pulmonary tuberculosis, and when found to have Klebsiella pneumoniae, the suggested treatment was monotherapy with ceftriaxone. The patient was treated parenterally initially, and then was treated for 3 weeks with oral ofloxacin.

Skin and Soft-Tissue Infections

Skin and soft-tissue infections are common problems in the elderly. In one study of nursing home residents, skin infections accounted for 35% of infections acquired in nursing homes in Maryland (1). The presence of a skin ulcer was the major risk factor for developing an infected ulcer or cellulitis. In addition to the normal changes of the aging skin such as decreased turgor, elasticity, and atrophy, elderly patients often have coexisting peripheral vascular disease or small-vessel disease of diabetes mellitus, which makes them increasingly vulnerable to skin and soft-tissue infections, and may result in delayed healing. The elderly are at risk for all the usual pathogens causing skin and soft-tissue infections but in addition, because of their impaired host defenses and frequent coexisting vascular disease and diabetes mellitus, the elderly are at greater risk of developing necrotizing soft-tissue infection, infected pressure ulcers, and diabetic foot infections (see also Chapter 22). Skin and soft-tissue infections in the elderly consist of the primary pyodermas, erysipelas or cellulitis, necrotizing fasciitis, and the infected ulcer (see Table 1).

West Nile virus aseptic meningitis and stuttering in woman.

To the Editor: West Nile virus (WNV), a mosquito-borne flavivirus, is closely related to St. Louis encephalitis virus and Japanese encephalitis virus (JEV). Most cases of WNV have been mild, but neuroinvasive disease has been observed, especially among older persons and immunocompromised persons (1,2). The most common neurologic manifestations of WNV are aseptic meningitis, meningoencephalitis, and encephalitis with or without acute flaccid paralysis (3). Other less common neurologic manifestations include Guillain-Barre syndrome, chorioretinitis, stroke-like symptoms, and unilateral brachial plexopathy (4,5). We report a case of WNV aseptic meningitis in a 39-year-old immunocompetent woman who had severe headache with new-onset stuttering. Her medical history included lumbar disc herniation and migraines, for which she was taking sumatriptan. Her symptoms started ≈2 weeks before hospitalization and included a severe generalized headache initially thought to be a migraine, but sumatriptan resulted in no improvement. A few days later, she had fever and was intermittently stuttering. She denied recent travel or animal exposure but admitted to having received multiple mosquito bites during the preceding weeks. At admission, she had a temperature of 101.3°F, pulse rate of 92 beats/min, blood pressure of 130/80 mm Hg, and respiratory rate of 16 breaths/min. She appeared mildly ill but was alert and oriented with no nuchal rigidity, photophobia, rash, or limb weakness. Results of a physical examination were unremarkable, and results of a neurologic examination were notable only for stuttering. Laboratory test results included a leukocyte count of 12,300 cells/mm3 (63% neutrophils, 29% lymphocytes, 7% monocytes, 1% basophils) and a platelet count of 204,000 cells/mm3. Other laboratory values were unremarkable, and levels of serum transaminases and creatinine phosphokinase were within reference ranges. Cerebrospinal fluid (CSF) was clear and contained 37 leukocytes/mm3 (2% neutrophils, 78% lymphocytes, 20% monocytes), 2 erythrocytes/mm3, a glucose level of 68 mg/dL, a protein level of 36 mg/dL, and a lactic acid level of 2.1 meq/L. No abnormalities were found on a cranial computed tomography scan. The patient began treatment with acyclovir, 10 mg/kg intravenously, every 8 hours for 3 days. On hospital day 2, she underwent magnetic resonance imaging of the brain; results were within reference limits. On hospital day 3, her headache began to improve and she became afebrile, but she still stuttered occasionally. Results of CSF tests for enterovirus, herpes simplex viruses 1 and 2, and varicella zoster virus and PCR for human herpesvirus 6 were negative, and acyclovir was discontinued. On hospital day 5, she was discharged. Three days later, serum and CSF ELISA results for WNV were positive. A WNV ELISA was performed at ViroMed Laboratories (Minnetonka, MN, USA) by using a Focus Test Kit (Focus Diagnostics, Cypress, CA, USA), and the result was positive. The patient subsequently reported that her stuttering had ceased. A high degree of clinical suspicion for WNV infection should be considered in patients with a recent history of mosquito bites and an acute febrile illness associated with neurologic signs and symptoms (5). Typical CSF findings of infection with WNV include lymphocytic pleocytosis, elevated protein level, reference glucose and lactic acid levels, and no erythrocytes (6). The clinical presentation of WNV infection varied widely from asymptomatic seroconversion to fatal encephalitis. It is possible, but unlikely, that the stuttering in the patient was an indication of a migraine aura. Initially, the patient reported that the headache might have been a migraine, but later reported that its associated symptoms, e.g., photophobia, were not as severe and did not last as long as her usual migraines. Further argument against migraine aura is the lack of response to her migraine medication and the fact that the stuttering continued after the headache resolved. Because WNV resembles JEV, it is interesting to note that a case of stuttering in a young adult infected with JEV has been reported (7). However, the mechanism of stuttering associated with WNV is unknown. One possible explanation is myoclonic contractions of the tongue, i.e., vocal myoclonus.