Milagros P. Reyes

Vancomycin during pregnancy: Does it cause hearing loss or nephrotoxicity in the infant?

Vancomycin was administered intravenously to 10 pregnant women for the treatment of methicillin-resistant Staphylococcus aureus infections. Auditory brainstem response testing and renal function studies were performed on the 10 babies in the experimental group and 10 babies in each of two control groups to determine the safety of vancomycin use during pregnancy. Auditory brainstem responses were not normal at birth in six infants from the three different groups studied (N = 30) but were normal at 3 months in five. The sixth infant had conductive hearing loss unrelated to vancomycin use that spontaneously disappeared at 12 months of age. Renal function was normal in all infants. Vancomycin was detected in cord blood in two patients and in breast milk in one. Adequate serum levels were achieved with routine doses in eight mothers tested; no adverse reactions occurred. It appears that vancomycin use during the second and third trimesters of pregnancy does not produce sensorineural hearing loss or nephrotoxicity in the infant.

Posterior Uveitis in Patients with Positive Serology for Syphilis

The clinical features and ophthalmologic findings of 20 patients with syphilitic posterior uveitis seen at the Detroit Medical Center from November 1993 through February 1996 were reviewed. The mean age was 58 years; 8 patients were male and 12 were female; and all patients were black. Three of 9 patients tested were HIV positive. Patients were divided into 2 groups: those with acute (8) and those with chronic (12) syphilitic posterior uveitis. Chorioretinitis was the predominant uveitic pattern (15/20). Eighteen patients presented with blurred vision. All patients had reactive serum fluorescent treponemal antibody, absorbed (FTA-ABS); 3 had nonreactive rapid plasma reagin (RPR). Mean RPR titer in the chronic uveitis group and in the acute uveitis group was 1:27.3 and 1:209.8, respectively. Seven patients had abnormal cerebrospinal fluid (CSF); CSF VDRL was reactive in 2 patients. All patients were treated with intravenous penicillin G. Eight of 14 patients seen at follow-up showed improvement of ophthalmologic findings. Syphilis should be considered in the differential diagnosis of posterior uveitis.

Coxsackievirus B3 myocarditis in C3H/HeJ mice: Description of an inbred model and the effect of exercise on virulence

The effect of forced exercise on the development of coxsackievirus 133 myocarditis in inbred C3H/HeJ mice was studied. Four groups of mice (30 per group) were formed: infected-exercised (Group I); infected-unexercised (Group II); uninfected-exercised (Group III); and uninfected unexercised (Group IV). Infected mice were inoculated intraperitoneally with 1.0 × 102.1 TCID50 coxsackievirus 133. Exercised animals were swum daily for 60 minutes on days 1–9. Myocardial viral titers were acutely elevated on day 3 of infection and were augmented significantly by exercise on days 6 and 9. Exercise increased the overall mortality from 0–10% to 20–40%; significantly increased heart: body weight ratios on days 6, 9 and 13; and increased the extent of myocardial fiber necrosis. We have reproduced the acceleration of C133 myocarditis by exercise in the inbred C3H model.

Placental histopathology in syphilis

Placental evaluation is important in congenital syphilis (CS) since clinical and serologic findings necessary to fulfill the diagnostic criteria of syphilis may be absent at birth, making early accurate diagnosis difficult. We examined 25 placentas from mothers with syphilis as confirmed by positive RPR rapid plasma reagin and fluorescent treponemal antibody absorption tests to determine which histopathologic features should raise the suspicion of CS. The 25 examined placentas were from 162 syphilitic mothers who delivered at our institution in 1990. Of the 27 infants delivered (including two pairs of twins), four were stillborn and three died at 1 day of age. Eleven of 23 liveborn infants fulfilled the Centers for Disease Control criteria of probable CS. Seven of the 25 placentas showed a well-defined constellation of histopathologic changes that included proliferative vascular changes, chronic villitis, relative villous immaturity, and, in six placentas, acute villitis. All seven of these placentas showed the presence of spirochetes by special stains. Six also had plasma cells in the basal decidua. Recognition of these placental changes, although nondiagnostic, should lead the pathologist to seek additional clinical history and ancillary tests. Placental histopathologic examination is an additional parameter to be considered in the diagnosis of CS.

Resurgence of Pseudomonas Endocarditis in Detroit, 2006-2008

A resurgence of endocarditis due to Pseudomonas aeruginosa was seen in 10 injection drug users (IDUs) in Detroit between 2006 and 2008 (6 men, 4 women; mean age, 48.1 yr). All patients tested negative for the human immunodeficiency virus (HIV). Five patients had left-sided endocarditis of the mitral valve and/or the aortic valve; 3 of 5 patients had prosthetic valve endocarditis. Four of 10 patients had right-sided endocarditis of the tricuspid valve alone. One patient had bilateral involvement of the aortic and tricuspid valves. Nine patients had Pseudomonas endocarditis (PsE); 1 patient had mixed endocarditis with P. aeruginosa and Candida parapsilosis. Seven of 10 patients were treated with a combination of intravenous cefepime, 4-6 g/d, plus high-dose tobramycin (HDT) for at least 6 weeks. Tobramycin, 8 mg/kg per day, was given as a single daily dose intravenously, aiming for peak serum levels of 18-22 &mgr;g/mL and trough levels of <1 &mgr;g/mL. The patient with mixed endocarditis was also treated with fluconazole. Two patients initially treated with other antipseudomonal regimens, including cefepime alone and piperacillin/tazobactam plus tobramycin, failed treatment and were switched to cefepime and HDT. A third patient was switched to cefepime and ciprofloxacin because of nephrotoxicity. Two patients developed nephrotoxicity to tobramycin; 1 patient developed ototoxicity. The overall medical cure rate for both left-sided and right-sided disease was 80% (4/5). All 5 patients who required surgery survived (5/5; 100%). Overall outcome was 90% (9/10). Indications for valve replacement were recurrent Pseudomonas bacteremia (n = 3), recurrent bacteremia and congestive heart failure (n = 1), and persistent bacteremia and fungemia (n = 1). Tricuspid valvulectomy with valve replacement was successful in 2 patients and in a third patient who had successful replacement of both the tricuspid and the aortic valve for recurrent bacteremia and congestive heart failure. Two patients with pure left-sided prosthetic valve endocarditis underwent successful repeat valve replacements. Although this is a small series, the overall mortality rate (1/10; 10%) was low. The patient who did not survive had left-sided involvement of the aortic valve and could not undergo surgery because of a large embolic cerebral infarct. The mortality rate of left-sided disease in the current series was 16.7% (1/6 including the patient with tricuspid and aortic valve PsE) compared to 60% in a series of 15 patients reported in 1990. Our current antimicrobial regimen for PsE consists of a combination of cefepime, 6 g/d, in 3 divided doses, plus HDT, 8 mg/kg per day, given as a single daily dose for 6 weeks. For cefepime-resistant Pseudomonas, imipenem, 4-6 g/d, or meropenem, 6 g/d, plus HDT has been successful. For right-sided disease refractory to medical therapy, surgical intervention is recommended if Pseudomonas bacteremia persists for 2 weeks on appropriate antimicrobial therapy or if bacteremia recurs after a 6-week course of treatment. Tricuspid repair/reconstruction or valvulectomy with valve replacement plus combined antipseudomonal regimen may be the optimal therapy for refractory right-sided endocarditis. This approach not only may prevent the development of severe and permanent impairment of right ventricular function, which is a complication of valvulectomy alone without valve replacement, but also may cure the infection. For left-sided disease, surgery is recommended if blood cultures remain positive for 7 days on appropriate antimicrobial therapy or if Pseudomonas bacteremia recurs after completion of a 6-week course of the combined regimen. Abbreviations: CFU = colony-forming units, CLSI = Clinical and Laboratory Standards Institute, HACEK = Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species, HDT = high-dose tobramycin, HIV = human immunodeficiency virus, IDU = injection drug user, MIC = minimum inhibitory concentration, PFGE = pulse-field gel electrophoresis, PsE = Pseudomonas endocarditis, TEE = transesophageal echocardiogram.

The resurgence of congenital syphilis: A cocaine-related problem

The relationship of maternal illicit drug use to congenital syphilis was studied in a population of newborn infants (N = 1012) who were screened for intrauterine exposure to illicit drugs by meconium analysis and whose mothers were screened for syphilis by the rapid plasmin reagin fluorescent treponemal antibody, absorbed (RPR/FTA-ABS) test. The result of the meconium drug screening was positive in 449 (44.3%) infants: 401 (39.6%) screening results were positive for cocaine, 71 (7%) positive for opiate, and 31 (3.1%) positive for cannabinoid. The maternal RPR/FTA-ABS result was positive in 72 (7.1%) women, and congenital syphilis was diagnosed in 46 (4.5%) infants on the basis of Centers for Disease Control and Prevention definitions. The incidence of positive RPR/FTA-ABS result (10.5% vs 4.4%) and congenital syphilis (7% vs 2.5%) was significantly higher (p < 0.01) among infants with positive results compared with those with negative drug screening results. Similarly, the incidence of positive RPR/FTA-ABS (11% vs 4.6%) and congenital syphilis (8% vs 2.3%) was significantly (p < 0.01) higher among infants with cocaine-positive results compared with those with cocaine-negative results. We conclude that maternal illicit drug use, specifically cocaine, is significantly related to the resurgence of congenital syphilis among newborn infants.

Chronic interstitial pulmonary fibrosis following mycoplasma pneumoniae pneumonia

An unusual case of chronic interstitial fibrosis that developed as a sequela of Mycoplasma pneumoniae pneumonia is described. Predominant manifestations included progressive exertional dyspnea, shortness of breath, persisting lung infiltrates, low lung volumes, and low pulmonary diffusing capacity. Open lung biopsy one year after the acute stage of mycoplasma pneumonia revealed focal interstitial fibrosis with early pleural thickening, hypertrophic alveolar lining cells, and peribronchiolar lymphoid cell infiltrates. Improvement in clinical manifestations, radiologic findings, and pulmonary function results occurred with steroid therapy.

Granulocytopenia Associated with Carbenicillin Five Episodes in Two Patients

Abstract Dose-related reversible granulocytopenias were observed in two patients receiving large amounts of carbenicillin intravenously, one for life-threatening Escherichia coli bronchopneumonia and the other for Pseudomonas spondylitis. After repeated relapses in the latter patient, carbenicillin was re-administered (three times) because of the absence of an alternative option. Severe granulocytopenias appeared after a mean dosage of 609 g of carbenicillin given over a period of about 16 days. In the bone marrow, myeloid but not erythroid precursors were depressed. Neither serum iron nor iron saturation was increased. Leukoagglutinins could not be demonstrated. We have continued to give carbenicillin in lesser suppressive amounts to one of these patients without leukopenia. This adverse reaction to carbenicillin is probably due to a cytotoxic effect and not to an immunologic mechanism.

Mouse Strain-related Variation as a Factor in the Pathogenesis of Coxsackievirus B3 Murine Myocarditis

Coxsackievirus B3 (CB3) is a well known cause of acute heart muscle disease in humans and experimental animals. After virus is cleared from the heart, a subacute myocarditis or cardiomyopathy may ensue and these conditions are thought to be due to host immune response. During the acute phase of myocarditis, however, the pathogenesis of myocardial fibre destruction remains uncertain. One theory proposing an immune mechanism is based on the 2 to 3 day delay in pathological changes observed after peak virus titres in the heart and their chronological synchrony with the development of cytotoxic T lymphocyte (CTL) activity in the spleen of infected animals (Khatib et al., 1980; Woodruff & Woodruff, 1974). Moreover, adoptively transferred, Cr-labelled sensitized T cells are re-routed to the heart at about the time when myocardial fibre damage becomes apparent by light microscopy (Reyes et al., 1984).

Coxsackievirus-positive cervices in women with febrile illnesses during the third trimester in pregnancy.

Coxsackievirus B5 infection was demonstrated in five of seven third-trimester pregnant women with undifferentiated febrile illnesses or aseptic meningitis. Coxsackievirus B5 was recovered from the cervix and throat in four women and from the rectum in three. No obvious illnesses were evident in the babies. These findings suggest that previously unrecognized cervical enterovirus carriage or infection is common in infected pregnant women in the last trimester and that subsequent neonatal infection at delivery may result.