This is a retrospective study of adult patients admitted to a large urban hospital, who had a nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) test and a lower respiratory tract culture within 48 hours of admission that the culture yielded Staphylococcus aureus. Results showed high sensitivity (93.3%) and negative predictive value (95.2%) of nasal PCR for MRSA in the lower respiratory tract. A nasal MRSA PCR test could guide the discontinuation of MRSA-directed empiric antibiotic therapy in patients who are unlikely to be infected with this organism.
The role at admission of nasal polymerase chain reaction (PCR) for patients with methicillin-resistant Staphylococcus aureus (MRSA) in guiding antibiotic therapy for lower respiratory tract infection is unknown.
To determine whether nasal MRSA PCR at admission can predict the absence of MRSA in lower respiratory tract secretions.
We performed a retrospective study of adult patients admitted to a large urban hospital. Patients had a nasal MRSA PCR test and a lower respiratory tract culture obtained within 48 hours of admission and the culture yielded S aureus.
Main outcome measures:
Sensitivity, specificity, and positive and negative predictive values.
Our results showed high sensitivity (93.3%) and negative predictive value (95.2%) of nasal PCR for MRSA in the lower respiratory tract.
With its high sensitivity and negative predictive value, a nasal MRSA PCR test performed within 48 hours of hospital admission could help guide the discontinuation of MRSA-directed empiric antibiotic therapy in patients who are unlikely to be infected with this organism. A prospective study is needed to confirm these findings.
Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia, estimated to cause 2 million deaths annually. The majority of pneumococcal mortality occurs in developing countries, with serotype 1 a leading cause in these areas. To begin to better understand the larger impact that serotype 1 strains have in developing countries, we characterized virulence and genetic content of PNI0373, a serotype 1 strain from a diseased patient in The Gambia. PNI0373 and another African serotype 1 strain showed high virulence in a mouse intraperitoneal challenge model, with 20% survival at a dose of 1 cfu. The PNI0373 genome sequence was similar in structure to other pneumococci, with the exception of a 100 kb inversion. PNI0373 showed only15 lineage specific CDS when compared to the pan-genome of pneumococcus. However analysis of non-core orthologs of pneumococcal genomes, showed serotype 1 strains to be closely related. Three regions were found to be serotype 1 associated and likely products of horizontal gene transfer. A detailed inventory of known virulence factors showed that some functions associated with colonization were absent, consistent with the observation that carriage of this highly virulent serotype is unusual. The African serotype 1 strains thus appear to be closely related to each other and different from other pneumococci despite similar genetic content.
Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) in at-risk adults. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), or immunologic ‘priming’ with PCV followed by ‘boosting’ with PPV in adults who recovered from pneumococcal pneumonia.
Subjects received PPV followed in 6 months by PCV, or vice-versa. IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline, 4–8 weeks and 6 months after each vaccination.
PPV and PCV stimulated similar IgG levels and OPK at 4–8 weeks. Six months post-PPV, antibody declined to baseline but remained modestly elevated post-PCV. PCV given 6 months post-PPV stimulated modest IgG increases that failed to reach post-PPV peaks. In contrast, PPV 6 months after PCV caused dramatic increases in IgG and OPK to all polysaccharides, consistent with a booster effect. Six months after the second vaccination, however, IgG and OPK in all patients fell precipitously, returning toward original baseline levels.
In high-risk subjects, the effect of PPV is short-lived; PCV stimulates a more prolonged response. PPV as a booster following PCV causes early antibody rises, but IgG declines rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults.
Pneumococcus; Polysaccharide; Vaccine; Protein-conjugate; Pneumonia
Noroviruses (NoVs) are increasingly being recognized as an important enteric pathogen. We investigated a nosocomial NoV outbreak at a university-based hospital that was originally attributed to Clostridium difficile infection (CDI). We describe the unique challenges and the important lessons learned in the identification of noroviruses as the true etiologic pathogen in an outbreak healthcare setting, where CDI is endemic.
norovirus; Clostridium difficile; nosocomial diarrhea
Longstanding controversy over the efficacy of 23-valent pneumococcal polysaccharide vaccine (PPV23) led to a recommendation by the Joint Committee on Vaccination and Immunisation (JCVI) of the United Kingdom in March 2011, to discontinue routine use of PPV23 in older adults.1 Following careful review of the evidence and feedback from stakeholders, the JCVI decided to retain the original policy of uniform vaccination of adults >65 years of age, while keeping the subject under continued review. In the United States, the Advisory Committee on Immunization Practices (ACIP) which is also concerned about the efficacy of PPV23 is currently considering a different strategy, i.e. adding 13-valent pneumococcal protein-conjugate vaccine (PCV13) for recommended use in adults, following recent Food and Drug Administration (FDA) approval for this purpose in adults over 50 years of age. It is therefore timely to review the options for prevention of pneumococcal disease in adults.
The impact of an Antibiotic Restriction Program (ARP) on the patterns of antibiotic use in the treatment of community-acquired pneumonia (CAP) was examined. We also evaluated the association between the ARP and the length of hospital stay in regard to CAP treatment and cost savings associated with the implementation of the ARP.
A retrospective cohort study of patients admitted with CAP was conducted at two six-month periods, one prior to the ARP and one after the ARP. The health system’s Computerized Patient Record System (CPRS) was used to obtain demographics, length of hospital stays, readmission rates, blood culture results, co–morbidities, antibiotic use, and durations of therapy. A total of 130 patients met the inclusion criteria for the final analyses. Average drug costs, employee salaries, and the cost of laboratory procedures were used to assess cost savings associated with the ARP.
From a total of 132 antibiotics that were ordered to treat CAP in the pre-ARP period, 28 were restricted (21.2%). However, the number of restricted antibiotics ordered was significantly reduced to 12 out of 114 (10.2%) antibiotics ordered in the post-ARP period (P = 0.024). In post-ARP implementation, mean length of hospital stay was also significantly reduced from 7.6 to 5.8 days (P = 0.017), and although not statistically significant, 30-day readmission rates declined from 16.9% to 6.2% (P = 0.097). The ARP was also associated with $943 savings per patient treated for CAP.
In addition to a decrease in the antibiotic utilization and the mean length of hospital stay, the ARP may have yielded cost savings and reduced the readmission rates for those patients admitted and treated for CAP.
Antibiotic restriction program; infection; antibiotics; hospital
Pneumococcal disease continues to cause substantial morbidity and mortality among the elderly. Older adults may have high levels of anticapsular antibody after vaccination, but their antibodies show decreased functional activity. In addition, the protective effect of the pneumococcal polysaccharide vaccine (PPV) seems to cease as early as 3 to 5 years postvaccination. Recently, it was suggested that PPV elicits human antibodies that use predominantly VH3 gene segments and induce a repertoire shift with increased VH3 expression in peripheral B cells. Here we compared VH3-idiotypic antibody responses in middle-aged and elderly subjects receiving PPV as initial immunization or revaccination. We studied pre- and postvaccination sera from 36 (18 vaccine-naïve and 18 previously immunized subjects) middle-aged and 40 (22 vaccine-naïve and 18 previously immunized subjects) elderly adults who received 23-valent PPV. Concentrations of IgGs to four individual serotypes (6B, 14, 19F, and 23F) and of VH3-idiotypic antibodies (detected by the monoclonal antibody D12) to the whole pneumococcal vaccine were determined by enzyme-linked immunosorbent assay (ELISA). PPV elicited significant IgG and VH3-idiotypic antibody responses in middle-aged and elderly subjects, regardless of whether they were vaccine naïve or undergoing revaccination. Age did not influence the magnitude of the antibody responses, as evidenced by similar postvaccination IgG and VH3 antibody levels in both groups, even after stratifying by prior vaccine status. Furthermore, we found similar proportions (around 50%) of elderly and middle-aged subjects experiencing 2-fold increases in VH3 antibody titers after vaccination. Age or repeated immunization does not appear to affect the VH3-idiotypic immunogenicity of PPV among middle-aged and elderly adults.
Several kinds of laboratory techniques are available to detect Clostridium difficile toxin in fecal samples. Because questions have been raised about the reliability of immunoassays compared to the accepted standard, cytotoxicity assay, we studied three enzyme immunoassays (EIAs) and one rapid EIA, which demonstrated relatively good sensitivities and specificities compared to cytotoxicity assay.
Haemophilus influenzae rarely causes spontaneous bacterial peritonitis. We describe a typical case of spontaneous bacterial peritonitis in which the causative organism was identified as nontypeable H. influenzae, biotype III. Infection progressed despite the presence of adequate serum bactericidal antibody, probably due to the absence of complement in ascites fluid.
An important theme that emerges from all early historical accounts is that in addition to the decreased virulence of Treponema pallidum, the incidence of secondary syphilis has decreased drastically over the past three centuries. Even in the early 20th century, most syphilologists were of the opinion that the disease had undergone changes in its manifestations and that they were dealing with an attenuated form of the spirochete. Such opinions were based primarily on the observations that violent cutaneous reactions and fatalities associated with the secondary stage had become extremely rare. The rate of primary and secondary syphilis in the United States increased in 2002 for the second consecutive year. After a decade-long decline that led to an all-time low in 2000, the recent trend is attributable, to a large extent, by a increase in reported syphilis cases among men, particularly homosexual and bisexual men having sex with men. The present review addresses the clinical and diagnostic criteria for the recognition of secondary syphilis, the clinical course and manifestations of the disease if allowed to proceed past the primary stage of disease in untreated individuals, and the treatment for this stage of the disease.
This study employs time-kill techniques to examine the most common drug combinations used in the therapy of methicillin-resistant Staphylococcus aureus (MRSA) infections, vancomycin plus either gentamicin or rifampin. Community-associated MRSA were more likely to be synergistically inhibited by combinations of vancomycin and gentamicin versus vancomycin alone compared to inhibition associated with hospital-acquired strains.
Previous studies of the antibiotic susceptibility of Streptococcus milleri group organisms have distinguished among species by using phenotypic techniques. Using 44 isolates that were speciated by 16S rRNA gene sequencing, we studied the MICs and minimum bactericidal concentrations of penicillin, ampicillin, ceftriaxone, and clindamycin for Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus. None of the organisms was resistant to beta-lactam antibiotics, although a few isolates were intermediately resistant; one strain of S. anginosus was tolerant to ampicillin, and another was tolerant to ceftriaxone. Six isolates were resistant to clindamycin, with representation from each of the three species. Relatively small differences in antibiotic susceptibilities among species of the S. milleri group show that speciation is unlikely to be important in selecting an antibiotic to treat infection caused by one of these isolates.
Nontypeable Streptococcus pneumoniae is a common cause of epidemic conjunctivitis. A previous molecular fingerprinting study identified a clone of nontypeable pneumococcus that was responsible for a recent outbreak of conjunctivitis. In the present study, we examined the extent to which pneumococci that cause sporadic cases of conjunctivitis are related to this epidemic strain. Using arbitrarily primed BOX-PCR, we have determined that, of 10 nontypeable pneumococci causing sporadic conjunctivitis, 5 were clonal and closely related to a previous outbreak strain, whereas 5 others were genetically diverse.
We reviewed the results of microscopic Gram stain examination and routine culture for 2,635 cerebrospinal fluid (CSF) samples processed in an adult hospital microbiology laboratory during 55 months. There were 56 instances of bacterial or fungal meningitis (16 associated with central nervous system [CNS] shunt infection), four infections adjacent to the subarachnoid space, four cases of sepsis without meningitis, and an additional 220 CSF specimens with positive cultures in which the organism isolated was judged to be a contaminant. Because 121 of these contaminants were isolated in broth only, elimination of the broth culture would decrease unnecessary work. However, 25% of the meningitis associated with CNS shunts would have been missed by this practice. The most common cause of meningitis was Cryptococcus neoformans, followed by Streptococcus pneumoniae and Neisseria meningitidis. In 48 of 56 (88%) of cases, examination of the Gram-stained specimen revealed the causative organism. If patients who had received effective antimicrobial therapy prior to lumbar puncture are excluded, the CSF Gram stain is 92% sensitive. Microscopic examination incorrectly suggested the presence of organisms in only 3 of 2,635 (0.1%) CSF examinations. Thus, microscopic examination of Gram-stained, concentrated CSF is highly sensitive and specific in early diagnosis of bacterial or fungal meningitis.
Seven patients with amebic liver abscess presenting as pleuropulmonary disease were admitted to hospital initially because of pulmonary symptoms and were found to have amebic liver disease. Three categories of pleuropulmonary involvement included reactive inflammation of the pleura or lung, rupture of a hepatic abscess into the pleural space and rupture of a hepatic abscess into the bronchial airways. The preferred medical treatment is with metronidazole, but rupture of hepatic amebic abscess into the pleural space requires drainage in addition to medical therapy. In contrast, rupture into the bronchus may provide spontaneous drainage so that only medical therapy is needed. Recovery from amebiasis in all three categories is generally complete. Morbidity and mortality increase with failure to correctly identify amebic infection of the liver as the underlying cause. Because, in new cases, no findings specifically suggest that pleuropulmonary disease is a complication of hepatic amebic abscess, this possibility needs to be considered, especially in persons who are at risk of having been infected with amebae.
The in vivo and in vitro immunoglobulin G plaque-forming cell responses to sheep erythrocytes (SRBC) are nearly obliterated during disseminated syphilitic infection (3 to 8 weeks post-intravenous injection) in rabbits. Splenic and lymph node cells obtained from infected rabbits during this time period were capable of suppressing the normal in vitro responses of uninfected, SRBC-primed cells. Cell-free washings of cells from infected animals were also suppressive. This finding coupled with the fact that treatment of infected cells with proteolytic enzymes abrogated the suppressive effect constitute arguments against involvement of a specific suppressor cell population. The incidence of elevated levels of circulating immune complexes in the sera of rabbits with disseminated disease was also significantly different from that of uninfected controls or infected rabbits before the onset or after the regression of lesions. When added to cultures of lymphocytes from uninfected, SRBC-sensitized rabbits, sera containing complexes caused dose-related suppression of the in vitro immunoglobulin responses. Unlike immune complexes, no correlation was found between the presence of mucopolysaccharide materials and the stage of infection or the ability of serum to suppress the immunoglobulin responses to SRBC.
Methenamine is frequently prescribed for patients who have chronic urinary infection to suppress bacterial growth during active infection or to prevent recurrence once an infection has been brought under control. We have examined the effect of methenamine mandelate and ascorbic acid on bacteriuria in para- and quadriplegics from a spinal cord unit. Patients with indwelling urinary catheters and those on a program of intermittent catheterization were included. No suppressive or prophylactic effect of this regimen was observed in any of our patients. Methenamine does not appear to be an effective antimicrobial agent in subjects who have an indwelling urinary catheter or in patients with spinal cord injury who are on intermittent catheterization. Since there appears to be reason to question the efficacy of methenamine in situations in which it is usually prescribed, evidence should be sought for a therapeutic effect in other cases. If no benefit is observed, the drug should not be used.
Suppression of cellular immunity during primary and secondary infection may explain, in part, the unusual clinical evolution of syphilis. We have previously shown that lymphocytes from normal subjects undergo blastic transformation when exposed in vitro to Treponema refringens. This response was suppressed in patients with syphilis. the suppression being unrelated to serum factors. In the present paper we studied lymphocyte response in vitro to T. refringens, T. reiter, and T. pallidum as well as to monilia and trychophytins. The response to these antigens was suppressed in patients with syphilis although the response to phytohemagglutinin. pokeweed mitogen, and streptolysin was normal. These data support the hypothesis that human infection with T. pallidum is followed by a complex interaction between cellular and humoral immunity, the former being suppressed in primary and secondary stages.
Using an in vitro system that simulates the dynamics of the urinary tract, we have shown that concentrations of formaldehyde ≥ 25 μg/ml can be achieved in urine containing ≥ 0.6 mg of methenamine per ml at pH ≤ 5.7 or ≥ 1 mg/ml at pH ≤ 5.85. Exposure to this concentration of formaldehyde for 2 h produced a measurable antibacterial effect. These studies suggest that an effective bacteriostatic level of formaldehyde is likely to be achieved with currently used dosages of methenamine when the urine pH is less than 5.7 to 5.85.
The American opossum is the only experimental animal that regularly develops bacterial endocarditis spontaneously. There was no relation between the ability of opossums to clear bacteria from the bloodstream and the subsequent development of endocarditis.
Several lines of evidence suggest that cell-mediated immunity (CMI) is suppressed in the early stages of infection caused by Treponema pallidum and becomes activated at the time that latency is induced. In the studies reported in this paper, rabbits were infected intravenously with T. pallidum and subsequently challenged with Listeria monocytogenes. Enhanced ability to suppress the growth of Listeria was detected in their livers between 3 and 5 weeks after infection with T. pallidum, corresponding to the onset and regression of the generalized syphilitic eruption. A second infection of T. pallidum 4 weeks after the first, at a time when suppression was beginning to wane, prolonged the listericidal activity. These observations support the hypothesis that infection by T. pallidum stimulates CMI, which, in turn, may play a role in inducing latency.
The response of lymphocytes from patients with syphilis and normal subjects was studied in vitro by using phytohemagglutinin (PHA), pokeweed mitogen (PWM), streptolysin O (SLO), and a preparation of Treponema refringens. Normal lymphocytes exhibited a dose-response curve to treponemes. Although lymphocytes from patients with primary and secondary syphilis responded normally to PHA and PWM, their response to SLO was suppressed and they failed to show significant stimulation by treponemes. Serum from syphilitic patients did not affect normal lymphocytes, and culturing lymphocytes from patients with syphilis in normal serum did not restore their responsiveness. Six to 10 weeks after syphilitic patients had been treated, the degree of stimulation by treponemes was the same as for normal subjects. These data give indirect support to the hypothesis that immunological suppression occurs during active infection with T. pallidum.
Acetohydroxamic acid (AHA) is a potent inhibitor of urease which prevents alkalinization of urine and stone formation in rats in the presence of infection caused by urease-producing bacteria. Because an antibacterial effect of AHA, and synergy between kanamycin and AHA have also been described, we studied the interaction between AHA and 12 antibiotics against 14 gram-negative bacteria. Synergy, sometimes to a striking degree, was found in 17% of interactions; however, antagonism was detected in 5%. Infecting organisms would need to be studied individually before the antibacterial effect of AHA and an antibiotic could be predicted.
In vitro testing shows nearly all strains of Proteus to be susceptible to methenamine. However, infection by urease-producing bacteria alkalinizes the urine in vivo and prevents generation of formaldehyde, the active metabolite, from methenamine. We have previously shown acetohydroxamic acid (AHA) to be an effective inhibitor of bacterial urease in vitro and in vivo. We now present data obtained by use of static and dynamic in vitro systems, which show that, by preventing urease-induced alkalinization of urine, AHA enables methenamine to exert its antibacterial effect against representative Proteus species.
Macrophages from mice infected with facultative intracellular organisms such as Listeria monocytogenes and BCG have been shown to resist infection by antigenically unrelated intracellular bacterial parasites. This study compares phagocytosis, bacterial growth inhibition, and oxidation of glucose by macrophages from normal mice, mice infected with listeria or BCG, or mice immunized with killed listeria in incomplete Freund's adjuvant. Macrophages from listeria- and BCG-infected mice ingested more listeria; 67 and 57%, respectively, had three or more cell-associated bacteria versus 22% of controls (P < 0.001). Peritoneal macrophages from listeria- and BCG-infected animals significantly (P < 0.001 covariance analysis) inhibited growth of listeria in suspension, whereas control macrophages had no such inhibitory effect. The rate of oxidation of glucose-1-14C was higher in macrophages from listeria- and BCG-infected mice than from either uninfected animals or those immunized with killed listeria. During phagocytosis of killed or live bacteria, or latex particles, the rate of glucose oxidation was increased (P < 0.01). These data suggest that the cellular immunity after infection by an intracellular organism is associated with an increase in metabolic activity of macrophages, namely, an increase in the rate of glucose oxidation resulting in enhancement of phagocytosis and killing.