Interesting Articles in 2002 Apr - Jun
The investigators conducted a 14-day, double-blind, placebo-controlled trial of fumagillin, an antimicrobial derived from Aspergillus. They administered 20 mg 3 times daily to patients with positive stool stain and polymerase chain reaction (PCR) for E bieneusi. Other causes of diarrhea were excluded. They monitored stool for spores, stool volume, and patient use of antidiarrheal drugs at baseline, end of therapy, and 2 weeks after therapy ended. They also performed sequential blood D-xylose testing for malabsorption. A total of 10 patients in each group were to be enrolled, with placebo recipients offered drug later.
A total of 12 patients (10 with AIDS, 2 transplant patients) were enrolled before the monitoring group stopped the study because of demonstrated efficacy of the drug. All patients were then treated. The shedding of organism disappeared in all treated patients but in none of the placebo recipients. Similarly, the treated patients had significant improvement in stool consistency, decreased stool weight, less use of loperamide, higher D-xylose concentration, and improved Karnofsky scores. The drug is known to produce significant thrombocytopenia; 3 patients had platelet counts < 75,000/mm3 and 3 had neutropenia < 1000/mm3. Toxicity fortunately appeared short-lived, and relapse occurred only in 2 AIDS patients.
While this drug appears to offer significant promise for an otherwise miserable disease, its toxicity warrants close monitoring. It is not yet available in the United States. Expect it to be available in the future on a compassionate-use basis for patients with microsporidial diarrhea.
The investigators screened and randomized 5257 elective surgical patients to receive mupirocin nasal ointment or placebo twice daily before surgery. Randomization was stratified to different surgical services, and 82.6% of patients received a minimum of 3 doses of drug or placebo before surgery. Pretreatment and preoperative nasal cultures were performed, and patients were systematically followed for a month after the operation. All patients received standard antibiotic prophylaxis as indicated. The primary end point was CDC-defined, culture-proven surgical site infection.
A power analysis suggested that 2023 patients would be needed in each group to demonstrate a 50% decreased rate of S aureus surgical site infections. An adequate number were screened, but only 3864 patients were enrolled, and only 3511 completed the study. Patients in both groups were demographically and clinically similar to those excluded or not completing the study. The only difference between the treatment and placebo groups was a greater proportion of placebo patients with renal disease (17.4% vs 14.9%, P = .04). Nasal carriage of S aureus was eliminated in 83.4% of mupirocin-treated patients compared with 27.4% of placebo recipients (P < .0001). Three to 5 doses of mupirocin eliminated nasal S aureus in 81.3% of carriers, while 6 or more doses eliminated it in 93.3% of carriers. Only 1% of those who were not carriers prior to the operation became so while taking mupirocin, while 5.9% of noncarriers who received placebo became carriers after the operation.
The overall rates of nosocomial infection, nosocomial S aureus infection, surgical site infection, and S aureus surgical site infection did not differ between the 2 groups.
Only in the subset of S aureus nasal carriers did mupirocin decrease nosocomial S aureus infection (4.0% vs 7.7%, odds ratio [OR] = 0.49, 95% CI = 0.25-0.92, P = .02). Mupirocin did not decrease S aureus surgical site infections in any group, even carriers.
Why such disappointing results despite previously described benefit in dialysis patients? Some patients were quite likely colonized in locations other than their nose, and those locations could have contaminated wounds. Also, since 6% of patients became newly colonized after surgery, it is quite likely that others were infected by strains carried by healthcare workers. This was confirmed by differences in pulsed-field gel electrophoretic patterns between strains colonizing noses and infecting wounds. This extraneous background infection coupled with a reasonably low presurgical carriage rate quite simply overpowered any benefit of decolonizing noses. Although it is possible that sampling patients' noses for S aureus and administering mupirocin to those positives prior to elective surgery may result in fewer nosocomial infections in that subgroup, it remains to be seen whether it will be truly cost-effective. At worst, use of mupirocin could lead to overconfidence in a drug, when the better predictor of infection is excellent patient preparation and surgical technique.
The investigators enrolled 148 infants born to 146 mothers in Dallas between 1989 and 1999 who had syphilis and little prenatal care. At the time of delivery, 73% of the women had early syphilis, 64% had received no treatment, and 20% had received treatment within 4 weeks of delivery. The children underwent a battery of clinical and laboratory tests for neurosyphilis, most (92%) on the day of birth. Seventy children (47%) had clinical, x-ray, or conventional laboratory evidence of congenital syphilis. These findings include rash, rhinitis, hepatomegaly, splenomegaly, and generalized lymphadenopathy. No child had abnormal neurologic signs or examination findings. Thirty-one infants had positive spinal fluid rabbit-infectivity tests. Because those with negative rabbit-infectivity tests were more likely to have received prior antibiotics, the investigators had to discard data for 72 of the 148 infants from their subsequent analysis.
Of the 76 remaining infants, 22% had positive rabbit tests. Based on this as the gold standard, the following tests had positive predictive value of > 80%: thrombocytopenia and positive CSF PCR assay. The following tests had positive predictive value of 60% to 79%: abnormal physical exam, abnormal bone radiograph, thrombocytopenia, positive CSF-VDRL, positive serum PCR, and CSF IgM immunoblot. Normal physical exam had a negative predictive value of 97%, as did negative serum or blood IgM immunoblotting. Unfortunately, any abnormality of CSF protein, VDRL, or white count had only 82% sensitivity.
The authors opine that central nervous system infection is infrequent among children with negative examination and conventional serum, CSF, and x-ray studies. Such children should receive a single dose of benzathine penicillin and close follow-up serotesting. If the full evaluation cannot be obtained, or if the child has any abnormalities, they should receive high-dose parenteral penicillin. Certainly, it would be better to treat than to miss a treatable disease. If it were widely available, IgM immunoblotting would help separate the sheep from the goats and could spare individuals from unnecessary therapy in resource-poor areas.
The investigators collected serum and sputum samples from 68 CF patient every 6 months for up to 180 months from enrollment. They used ELISA tests for antibody against P aeruginosa cell lysate antigens from strains PAO1, FRD, and UWP100, as well as antibody against commercially purified exotoxin A and elastase. They quantified isolates from throat swabs or expectorated sputa and monitored clinical and x-ray changes. Finally, they used a stepdown regression model to ascertain relationships between positive serology and a large number of social, economic, and medical risk factors.
The median time to a titer of 1:256 against cell lysate was 17.8 months; exotoxin A, 24.2 months; and elastase, 70.9 months. The first 2 occurred 6-12 months before cultures were positive. Early exotoxin A serology was highly associated with 1 of the 2 centers (OR = 6.52, 95% CI = 2.87-14.80, P < .001). This center was originally crowded and mixed patients of different ages in the waiting room. Oral non-antipseudomonas antibiotic use (OR = 1.96, P = .02) also was associated with earlier exposure. Interestingly, there was an unexplained negative association with family income (OR = 0.56, P = .001) and care provided by a single physician from 1985-90 at the higher risk center (OR = 0.23, P < .001)
Based on these results, the authors urge neonatal screening for CF and segregation by age of positive patients. This is to avoid exposure to infected older CF children. If children are identified early, they might avoid unnecessary and risky hospitalization for diagnosis of unexplained symptoms. The authors also recommend discontinuation of long-term and prophylactic use of antibiotics in young children with CF. Institution of these measures may delay pseudomonal colonization and infection. Early infection might also be recognized months before sputum cultures or symptoms appear, potentially allowing earlier therapy that might be beneficial in preventing established chronic infection.
The investigators asked a simple question: are there enteric pathogens in the table sauces of Mexican restaurants in Mexico and Houston? For a group that has been studying traveler's diarrhea in Guadalajara for decades, it is surprising no one has asked the question before. They obtained 71 sauces of various types from 36 popular Guadalajara restaurants and 25 similar sauces from 12 popular Mexican non-chain restaurants in Houston. After determining the pH of the sauce, the researchers processed the sauce by dilution, homogenization, and then plating onto MacConkey agar plates. They enumerated the amount of E coli in the samples and subjected the isolates to DNA hybridization and Hep-2 adherence assay to determine whether isolates were enterotoxigenic or enteroaggregative E coli, respectively.
The investigators noted that all the sauces in Mexico were sitting on the tables at room temperature, while the sauces in Houston were brought to the table cold. The Mexican samples all contained non-E coli enteropathogens (not specified), and 66% grew E coli, with a median count of 1000 colonies per gram of sauce. Of the Houston samples, 40% grew E coli, but the median colony count was 0. These differences were significant (P < .03). Of the sauces, Guadalajara guacamole was the most frequently contaminated, but pico de gallo had the highest colony counts. Enterotoxigenic and enteroaggregative E coli were found in 9% and 44% of Guadalajara sauces, respectively, but in no Houston sauces. Sauce pH was not related to risk of contamination.
It would appear that sauces probably become contaminated either in preparation or through use at the tables in Guadalajara. The ambient table temperature may be enough to sustain or encourage growth of the bacteria. In Houston, serving refrigerated pre-prepared sauces to each patron probably decreased the risk of infection, even if contaminated. Although low pH is commonly thought to prevent bacterial growth, the pH of these sauces (4.6-4.9) was insufficient for inhibition. This paper provides physicians a practical bit of advice to give their traveling patients.
The authors searched multiple library and electronic resources to find 8 randomized, controlled trials comparing chlorhexidine and povidone-iodine solution preparation for venous catheterization. End points in the studies were catheter colonization and catheter-related bloodstream infection. They provided subgroup analysis as available for risks of infection in central, central-tunneled, and peripheral catheters relative to the 2 solutions used for preparation. They also performed extensive sensitivity analysis.
The 8 studies involved a total of 4143 catheters (1493 central venous, 1361 peripheral venous, 704 peripheral arterial, 395 pulmonary arterial, 75 peripherally inserted central venous, 62 introducer sheaths, and 53 hemodialysis). Individually, 6 of the 8 studies showed chlorhexidine to be associated with less risk of colonization, and only 1 of 7 were associated with less risk of bacteremia, although 5 of the remaining 6 had a trend toward decreased risk. The summary risk ratio, however, was 0.49 (95% CI = 0.31-0.71) for catheter colonization and 0.49 (95% CI = 0.28-0.88) for bacteremia after chlorhexidine scrub. The absolute risk reduction was 7.1% for colonization and 1.1% for catheter-related bloodstream infection. Chlorhexidine risk ratios for both bacteremia and colonization were similarly about 0.50 for all catheter types, all locations of patient care, and varying degrees of stringency of clinical diagnosis.
While the results of a meta-analysis are only as good as the quality of the individual studies of which it is comprised, the larger numbers of cases afford meta-analysis considerable power. There are obviously a number of problems that can occur, including, most significantly, reporting bias, in that negative reports are less likely to be published. Definitions may differ in different studies as well, but this can often be overcome by examining data presented. This meta-analysis appears valuable to the clinician in making a decision about which solution is best for skin preparation before catheterization. The authors express some concern for toxicity and agree that the more expensive chlorhexidine might not prove cost-effective for low-risk patients. With time, data will be available on this point. Until then, it would seem prudent to use chlorhexidine over povidone-iodine for patients at highest risk of infection.
The investigators prospectively evaluated all patients with bacteremia at their 1150-bed university hospital, which services an elderly population in central Tel Aviv. After hearing of a positive blood culture, they sent an experienced infectious disease physician to evaluate the medical record of each case, determine the likely source, and obtain missing information from caregivers and outside records if needed. They excluded usual contaminants from consideration. Finally, using a preconstructed 4-group classification of the time/location/means of acquisition of the bacteremia, they compared etiology and outcome of the groups.
A total of 1028 episodes of bacteremia occurred among 912 patients. Of these episodes, 604 were detected within 48 hours of admission and were thus considered community-acquired. These were ultimately grouped as follows:
Group A: true community-acquired (61%)
Group B: patients discharged 2-30 days previous to current admission (18%)
Group C: outpatient procedure or device-related (9%)
Group D: nursing home-acquired infection (11%)
Patients in Group D were significantly older than those in the other groups (83 years vs 66-71 years), had higher fatality rate (47% vs 16% in Group A), and were more likely to die from infection (35% vs 11% in group A). As expected, Group C was associated with vascular devices and Group D with Foley catheters. The predominant organisms reflected these devices. Even so, E coli and Enterococcus were the most common causes of "true" community-acquired bacteremias (49% and 31% respectively). Also, Group D patients were significantly more likely than Group A patients to have Proteus group organisms and organisms resistant to ceftazidime, gentamicin, ciprofloxacin, ceftriaxone, and cefuroxime.
For the clinician, this new schema may be useful to recognize higher risk of specific infections among patients from nursing homes, recently discharged from the hospital, or getting intravenous therapy at home. The patients in Groups B, C, and D are obviously sicker than those in Group A, and likely would spend more time in the hospital and have higher costs and fatality rates. It seems likely that hospitals and physicians stand to gain the most by recognizing sicker diagnosis-related group subsets of community bacteremias, thereby establishing risk stratification for expected outcome and payment. At the same time, patients may benefit by prompting physicians to consider more specific and aggressive empiric therapy for such patients.
The investigators organized the trial using specific definitions of infection and outcome, using 104 sites on 4 continents from July 1998 to July 1999. The inclusion criterion was a hospitalized patient with presumed MRSA infection. Therapy consisted of linezolid 600 mg IV twice daily or vancomycin 1 g IV twice daily for at least 7 days. When improved, the linezolid patients could be switched to oral therapy at the same dose. Patients could receive concomitant gentamicin or aztreonam, and the specific duration of therapy was reasonably broadly defined. Physicians assessed their patients at the end of therapy for clinical improvement and for microbiologic test of cure at a later visit. The investigators stratified results according to populations based on intent to treat, microbiologic etiology, and whether they adhered to protocol. Although not expressly stated, it can be assumed that the maker of linezolid sponsored the study.
Unfortunately, the study, despite enrolling and randomizing 460 patients, did not achieve the minimum 142 evaluable MRSA-infected patients in each group to exclude type 2 error. Only 56 evaluable MRSA patients received linezolid and 60 received vancomycin. The major cause for this difficulty was lack of microbiologic confirmation of MRSA in 50% of each group, resulting in early discontinuation of drug and inability to evaluate efficacy. Nevertheless, this is apparently the largest reported randomized comparison of these drugs to date.
There was no difference in clinical outcome (73% "cured" in both groups) or microbiologic outcome (59% to 63%) in the most important group, the evaluable MRSA-infected patients, or, for that matter, in any of the other groupings. Overall, both groups of patients had similar mild adverse reaction rates, with a higher rate of diarrhea (3.8% vs 0%) and thrombocytopenia (10% vs 3%) in the patients who received linezolid. Although 60% of patients with linezolid were switched to oral therapy, the 2-day difference in duration of hospitalization (14 vs 16 days for vancomycin patients) was not statistically significant (P = .08).
Although this is the best study available to date based on its size and quality, it still does not offer the clinician the definitive answer on which drug should be used. A formal cost-efficacy study should be performed that includes both intent-to-treat and actual evaluable MRSA-infected patients.
Inuit peoples in Nunavik, the northern region of Quebec, traditionally hunt walrus as part of their subsistence diet. An estimated 2% to 4% of walrus are infected with Trichinella, which unfortunately results in periodic large outbreaks in communities due to raw meat consumption. Because of these epidemics, the health and community authorities established a prevention program consisting of flying meat samples to a regional laboratory for PCR testing prior to consumption. Samples are precisely tagged to specific pieces and carcasses of meat. At the lab, meat is digested, with DNA extraction and analysis performed using Trichinella-specific DNA primers. Results are then called back to the community, where meat is either released or destroyed. By 1997, 6 of 8 Nunavik communities participated in this program, with an average of 7 days between the day of the hunt and reporting of the results. Most of this time was waiting for aircraft to take the meat to the laboratory.
In September 1997, 2 of 5 walrus harvested by one group of hunters were found positive. By the time the call came back to the community 6 days later, meat had already been distributed. Because it was tagged, 40 households had contaminated meat removed and destroyed. Nevertheless, it was found that 27 people had already eaten the meat either raw or cooked. Mebendazole postexposure prophylaxis was given at 100 mg twice daily for 3 days to 16 such individuals. While they were followed for signs of disease, 2 cases were newly identified who hadn't heard about the problem, as well as 2 more cases in a community 200 km away. This latter group included 5 other people who received a gift of walrus meat from the supposedly embargoed sample. Ultimately, 2 of 4 individuals who consumed raw walrus meat without prophylaxis developed clinical disease, as well as 1 of 16 who consumed cooked meat without prophylaxis. Three of 11 persons who ate raw walrus and were later given mebendazole experienced asymptomatic ELISA antibody seroconversion.
Since this outbreak and its attendant publicity, other communities have avidly participated in the program, resulting in 98% of walrus being screened. In 2001, 11% of walrus were infected, and no participating communities suffered any infections. This represents a remarkable community and public health achievement and would serve as a model for cooperative effort in other locales.
The investigators, from The UK Meningococcal Carriage Group, obtained oropharyngeal swabs from adolescents aged 15-17 in multiple locations before a massive group C conjugate vaccine program was instituted in November-December 1999.
They repeated the sampling on 16,583 adolescents a year after the immunization campaign, which reached approximately 70% of the population younger than 18 years of age. Approximately 7% of individuals participated in both samples.
Between the 2 periods, there was a significant drop in meningococcal disease in children younger than 18 years of age. The percentage of individuals carrying all serogroups of meningococcus, serogroup B, serogroup W-135, serogroup Y, and non-groupable strains did not change. The serogroup C carriage dropped from 0.45% to 0.15%, (OR = 0.34, P = .0013). Based on a carriage rate of 0.127% in vaccinated vs 0.342% in unvaccinated individuals in 2000, the vaccine had a calculated protective effectiveness against carriage of 63%, while the overall carriage rate dropped by 66%. The nature of those serogroup C isolates in vaccinees remains to be characterized.
This study must be considered preliminary, in that the duration of protection from carriage is unknown. Also, it is not clear that herd immunity is really playing a role, since the serogroup C carriage rate in the unvaccinated group dropped from 0.45% only to 0.342%. At the same time, the consequences of waning circulation of serogroup C strains in the population are unclear if major epidemics are caused by new clones for which the vaccine offers little protection. In the same vein, could there be a need to reimmunize teenagers now who received the conjugated Haemophilus influenzae B vaccine years ago? There is no doubt that conjugated vaccines have been a major advance. They appear to have an effect on decreasing the incidence of both disease and carriage. How best to maintain this desirable state of affairs needs to be determined.
The investigators conducted active and passive surveillance for cases of murine typhus in the Corpus Christi area during 1997-1998. Case definition was a compatible syndrome of fever, headache +/- rash, and a 4-fold rise in indirect immunoflurorescence assay (IFA) titer to R typhi. During 1998, they subjected trapped and subsequently euthanized opossums to ELISA dot technique assay for antibodies to R typhi and to IFA assays for R typhi and R felis. Fleas were combed from the opossums, ground up, and assayed by PCR for R felis. Finally, a geographic correlation was made between cases and location of trapped seropositive opossums.
During May-June 1997, there was an apparent increase in the number of cases of murine typhus in Corpus Christi. Patients ranged from 5 to 79 years in age. Fifty-five percent were Hispanic and 62% female. Symptoms included fever (100%), headache (56%), nausea/vomiting (51%), malaise/fatigue (44%), rash (27%), myalgia (22%), and diarrhea (20%). Only 15% of patients reported a history of fleabite, and only 13% had exposure to cats and 11% exposure to opossums. Serologic studies on 149 opossums showed 25% EIA seropositive to R typhi, with 8% positive to R typhi by IFA and 22% positive to R felis by IFA. (There is probable cross-reaction on both assays.) There was good correlation between the home of patients and trapped seropositive opossum, with 58% of patients living within the maximal range of a positive trapped opossum. Of the 3401 collected fleas (mean 23/opossum), over 99% were the cat flea Ctenocephalides felis. There were 529 fleas from 144 opossums tested by PCR. One percent of these fleas were positive for R typhi and 2% positive for R felis.
This study is interesting in that opossums are a huge nuisance in Corpus Christi and some other areas of the Southwestern United States. Although trapped in great numbers (> 6000 per year in Corpus Christi), they are capable of establishing a zoonotic cycle involving cat fleas and possibly cats. The cat flea is rather nondiscriminating in its taste and apparently aggressive enough to attack humans. R felis can maintain itself in fleas by transovarial infection. All of this leads to a high potential for human infection. Clinicians in the United States should ask their patients with unexplained fever about the possibility of exposure to cats, cat fleas, and opossums. A short course of doxycycline for those with affirmative answers may be curative.
The investigators performed a retrospective review of all cases of Group G streptococcal bacteremia identified through laboratory and clinical records at their 550-bed community hospital between 1990 and 1999. They used conventional microbiologic methods and analyzed trends using publicly available software. They then compared their results with previous reports.
The annual rate of bacteremia with Group G streptococcus steadily increased from 0/1000 admissions in 1990 to 0.41/1000 admissions in 1999 (trend P < .001). By 1999, there were more patients with bacteremia from Group G than Group A streptococci. Group G constituted 1.3% of all bacteremias. Throughout the study period, the mean rates of Group A bacteremia and all bacteremia were stable at 0.4 +/- 0.1 /1000 and 28/1000 admissions, respectively. Important demographic and clinical characteristics of the Group G-infected patients included age > 75 (63%); male gender (80%); skin source -- including pressure sore, usually of the lower extremities (93%); unspecified "complications" (33%); and mortality (15%).
In contrast to previous case series, this report did not demonstrate a high rate of endocarditis or underlying malignancy in the patients with this infection. The authors attribute this to their patients being representative of community dwellers, rather than very ill hospitalized patients. This report does demonstrate that streptococcal skin infections in infirm elderly men may be increasing and have significant consequence. Clinicians should be alert to this disease in their own patient population.