Gabriel-Adrian Popescu

Meningitis due to an unusual human pathogen: Streptococcus equi subspecies equi.

Streptococcus equi subspecies equi is involved in human infection. We present a case of meningitis in a 75-year-old patient with a favorable outcome after ceftriaxone and dexamethasone therapy. To our knowledge, it is the first case reported in an adult.

In the era of broad spectrum antibiotics, is ampicillin still an option?

Background In the era of broad spectrum antibiotics it is sometimes difficult to choose the best antimicrobial regimens. Because of misuse and abuse of antimicrobial usage, the level of resistance is increasing and sometimes we do not have treatment options. Infectious diseases specialists traditionally have the leadership role in optimal use of antimicrobials. Antimicrobial stewardship represents a worldwide accepted concept in order to preserve currently available antibiotics.

The long journey of outpatient parenteral antibiotic therapy in infective endocarditis: from idea to clinical guidelines.

Infective endocarditis (IE) is one of the bacterial infections which usually necessitates long-term antimicrobial treatment, 4 to 6 weeks, and in some situations, even longer. Classically, the IE patient is considered at risk for unexpected complications throughout the duration of therapy and remains hospitalized for this period, with high costs. Two methods have been proposed in order to reduce the financial burden for hospitals: a reduction of antimicrobial course duration and outpatient parenteral antibiotic treatment (OPAT) as completion of therapy after an initial period of hospitalization. Only in very few select cases, a shorter duration of two weeks was accepted, for fear of lack of bacterial eradication and recrudescence risk; the other option, outpatient management of IE, was considered with skepticism, because of the occurrence of acute heart failure, stroke, and severe arrhythmias even during appropriate antimicrobial treatment. However, more than 30 years ago, in 1978, one of the first papers about outpatient therapy in IE was published in The Western Journal of Medicine; and the pros and the cons of this idea are the same, three decades later. First, a good working medical system to deliver intravenous treatment at home, with adequate patient surveillance, is a requirement for OPAT management for IE; a peripherally inserted central catheter (PICC) is a largely accepted solution for antibiotic administration at home, used in up to 79% of all OPAT cases for endocarditis, in a report published in this issue of Southern Medical Journal by Larioza et al. The health system needs to allow a good patient evaluation and hospital monitoring for at least the first week of treatment; after hospital discharge, a fast re-admission of the patient if an unfortunate event occurs, and continuous evaluation for the surgical treatment indications. Second, some antimicrobials active for the most involved germs in IE, with a longer half-life, enabling one administration daily, are needed; among discussed options, ceftriaxone has some advantages: good activity against all streptococci (without Enterococcus spp), and against Haemophilus species (H parainfluenzae, H aphrophilus, and H paraphrophilus), Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species (HACEK group), a favorable pharmacokinetic for endocarditis, and a half-time of 7–9 hours, permitting a daily administration (i.e. 28 doses of ceftriaxone for a 4-week treatment course instead of 168 doses for ampicillin). The potency as inflammation inducer is lower for ceftriaxone as for other third generation cephalosporins, due to a lesser stimulation of PBP3. The American Heart Association (AHA) recommends ceftriaxone 2 g/day for 4 weeks for OPAT; several studies indicated a good outcome with ceftriaxone: 0–4% lethality for 28 days and 2–3% bacterial recrudescence. Another option, teicoplanin, in a small study, represented a good choice for OPAT in staphylococcal endocarditis, with an 80% clinical success rate; but teicoplanin is not available in several countries, including the United States. Moreover, teicoplanin and daptomycin, both convenient for OPAT because of daily administration, must be used as reserve antibiotics for IE due to multiresistant Gram-positive cocci; an overuse increases the pressure selection for antimicrobial resistance. In the report by Larioza et al, the most used antibiotics are beta-lactams and aminoglycosides. The third condition is the need of a prescriber to decide to monitor this patient at home and the patient’s acceptance for OPAT management. Obviously, an inclusion of OPAT in clinical guidelines could solve this last problem. Several clinical and etiological situations have enjoyed a better acceptance of OPAT; the AHA’s 2005 and the European Society of Cardiology’s (ESC) 2004 guidelines consider OPAT for patients with streptococcal endocarditis due to strains highly susceptible to penicillin. The selected patient needs to have a lower risk for heart failure or for embolism (no pulmonary or systemic emboli; no heart failure or acute aortic regurgitation; a small vegetation less than 10 (or 20) From the Matei Bals Infectious Diseases Department, Carol Davila University of Medicine, Bucharest, Romania.

The Starry Heaven and the Crowded Shelters: Public Health Risks

Starting in 1890, after the most important scientific revolution in microbiology, when Koch first presented his postulates, medicine was never the same. And, not only medicine itself and the medical approach to illness but society and social interventions as well. Administrative measures, such as isolation of presumably transmissible diseases were implemented soon after the idea of contagious diseases came in the spotlight. Isolating homeless people with a transmissible disease is a difficult task. Moreover, living in places with high human density, such as shelters, actually contributes to the spread of communicable infectious diseases. Fortunately, scientific advancements led to the development of vaccines, limiting the role of isolation measures. Primary prevention, by vaccinating susceptible populations, significantly reduced the number and extent of the outbreaks and also reduced the overall morbidity due to the interaction between infectious diseases and a number of chronic diseases. Targeted populations, such as the homeless, usually exhibit certain characteristics that make them more susceptible to acquiring infectious diseases (living in shelters, lower levels of immunity, etc) and to a higher level of associated morbidity (eg decompensation of chronic diseases). The health status of the homeless could represent a clinical and public health problem, due to a higher morbidity and mortality rate as compared to the general population and due to the costs of healthcare and the risk of communicable diseases outbreaks, respectively. Even if these risks are obvious, the burden is difficult to evaluate; the studies of homeless people are rare and provided data have several limitations: almost all are based on self-reports of interviewed people, the selection of populations is biased by a great percentage of refusal to participate or by clinical criteria (hospitalized patients), and frequently long-term homeless patients are over-represented. In this context, the paper published in this issue of the Southern Medical Journal by Wiersma et al represents a valuable enterprise due to the determination to address this rather neglected subject. Respiratory infections are, along with skin infections, the main acute pathology of homeless individuals. Of the very high proportion of respiratory symptoms reported by Wiersma et al, 57.7% could be related to a specific epidemiological situation with an ongoing outbreak of invasive pneumococcal infections. Older studies described a particular epidemiological evolution for respiratory infections in homeless people: the spread from shelter to shelter because of the frequent moving of individuals, without a higher risk for non-shelter population. An estimation performed in Toronto indicated that a shelter user had contact with a mean of 120 other residents in eight days and with 218 if they used more than one shelter in this period of time. However, for more contagious diseases, like influenza, the homeless people involvement in outbreaks spread in the general population could be an important one; the increase in their number and mobility could contribute to this, and preventive measures will be essential to limit the spread of epidemics. In Wiersma et al’s study the percentages of the influenza vaccinated homeless population are quite similar to those of the rest of the population; this finding is notable considering this is a very unstable population in terms of location and access to healthcare. The pneumococcal vaccination coverage still needs improvement in this population at high risk for respiratory infections. Concerning nonvaccine preventable diseases, the Toronto severe acute respiratory syndrome (SARS) experience in 2003 provided several insights for outbreaks in cities with large populations: the need for coordinated public health and homeless service agencies efforts, infection control in shelters, and resource allocation to address the health status of homeless people before and during an epidemic. The harder task will be to locate homeless people who require isolation or quarantine and to ensure their adherence to these restrictions. The mean age of the homeless population increases in many geographic areas and this increases the risk of chronic pathology; a recent study indicated that 85% of homeless persons over the age of 50 had at least one chronic medical condition. In Wiersma et al’s study 36.5% of participants were older than 50 years (median age, 46 years), which is consistent with data from another study that found an increase of median age from 37 to 46 years during a 14-year survey period in San Francisco (1990–2003). In Atlanta 46.2% of 123 participants reported one or more chronic medical condition; this level of chronic problems is certainly underestimated, considering that no participants reported HIV infection when this group is known to be at high risk for this condition. These chronic conditions represent a burden on the health system, and economic analyses indicate that effective primary care for these people could reduce the total costs by limiting the number of admissions in acute care hospitals and the mean duration of hospitalization; encouraging results were obtained in the United Kingdom by involving specialized and partly specialized general practitioners in homeless people care. Even though it might sound utopian at this From the Morristown Memorial Hospital, Morristown, NJ.

HIV-related disparities: it is not all about HAART accessibility.

Simple is not always true or useful in medicine and in particular in public health, where most phenomena have multiple determinants; the lack of data could complicate the attempt to understand some epidemiological situations and leaves an open territory for debate. Studies performed since the first years of the AIDS epidemic described one or more factors related to disparities in clinical outcomes of HIV-infected people; social status, gender, drug usage, sexual minorities, race/ethnicity are the determinants more frequently involved as explanations for these differences. The outcome of HIVinfected people was greatly improved after the introduction of the highly active antiretroviral therapy (HAART) in 1996. But, at the beginning, HAART was available only in some countries; the late and incomplete access to HAART in subSaharan Africa, the region with the largest number of people living with HIV infection, aggravated the racial disparities and the injustice feelings at the global level. Another factor contributed to this perception: even in developed countries, the access to medication was more difficult for people belonging to some minority groups. The situation could be considered as a denial of the right to health as it is defined in international treaties because of: unavailability of HIV-related structures, services or goods; existence of cultural/social/religious barriers to access prevention, diagnosis and/or treatment; disparities in accessibility and lack of quality of HIV management 1 In the past decade racial/ethnic disparities were registered in the United States, with a better clinical outcome for whites when compared with Hispanics or with black Americans, despite the general access to antiviral medication. However, many studies describe only the differences without any explanatory approach, allowing a hypothesis about inequities in the quality of antiretroviral treatment. An attempt to assess the differences in the quality of prescribed therapy was performed for the specific case of white and black people with HIV infection on antiretroviral treatment and the results are published in this issue of Southern Medical Journal. The selected indicator was the percentage of patients on treatment with antiretrovirals who received a HAART regimen. The analysis of a high amount of dataValmost 3 million HIV/AIDS patient visits for a period of 11 yearsVrepresents a very good way to obtain results with great statistical significance; the authors concluded that access to HAARTwas lower for black patients during the years 1996Y1999, but the access rates were similar for both groups of patients since 2000. The authors’ statement could be true, and probably it is related to the access to HAART. Unfortunately, the HAART/all antiretroviral regimens ratio is an imperfect indicator for quality of prescribed therapy. Indeed, some HAART regimens could be inadequate for a given patient due to some pre existing conditions or to opportunistic infections; for example a greater use of nonnucleoside reverse transcriptase inhibitors and a lower use of protease inhibitors (PI) in black American patients, as indicated by authors, could be scientifically sustained as related to more frequent associated infections (ie, tuberculosis); but the database doesn’t include such data and in their absence it is possible to speculate about a greater efficacy of regimens containing PI, more frequently prescribed for white patients. The authors themselves mentioned several other limits of their study: the absence of data concerning the disease stage at the moment of starting therapy (demonstrated to be related to life expectancy), the patients’ adherence to therapy and the missing visits with delayed failure diagnosis (determinants of durability of treatment success). In most parts of the world the same situation exists: equality of access, but disparities of HIV infection outcomes in some groups (ie, defined by age, social status, drug usage, ethnicity) due to the lack of adherence to treatment and to monitoring: virologic failures, viral multiresistance, and heavy burden of associate infections; the explanation often consists in a specific attitude concerning health status and health care. In other countries the formal rights do not imply a real accessibility to healthcare services because of medication shortages, the complete unavailability of medication or a restricted access related to nonmedical criteria. In 2008, the United Nations performed a global analysis of response to HIV at a national level; at least 84 of 133 reporting countries indicated some laws or policies that represent obstacles for the access to Invited Commentary

Immunocompromised host (especially HIV-positive) the target of pyomyositis in temperate regions.

Pyomyositis is an acute endemic infection, initially seen in tropical areas. Over the last several years, however, more cases have been reported in temperate areas, especially among patients with immunodeficiency. This increase could reflect the use of more advanced imaging techniques, but also corresponds to a rising number of immunocompromised patients. In these patients, the incidence of pyomyositis is relatively low, at 1.5 to 3.5 cases per thousand patient years. Less frequently, pyomyositis occurs in patients with diabetes mellitus, rheumatoid arthritis, malignancy, intravenous drug use, hemophilia, and in conjunction with central venous catheter use. IV drug use and muscle injury due to trauma or exercise are recognized risk factors in HIV-positive patients. Pyomyositis has 3 clinical stages: the first, “invasive,” with localized pain; the second, “suppurative,” when local tumefaction and fever appear; and the late stage, with sepsis and systemic disease. Clinical progression in the early stages is often insidious, and symptoms may be absent, making early diagnosis difficult. In more advanced disease, clinical deterioration can be precipitous. Pyomyositis usually involves a single muscle group, but in HIV-positive patients, it may involve multiple sites. Because of the rarity of pyomyositis in temperate areas, the disease is often diagnosed late. Antimicrobial treatment without a clear diagnosis may alleviate the symptoms, making diagnosis difficult. It is therefore important to keep pyomyositis in the differential diagnosis, especially in HIV-positive patients. An MRI examination should help identify muscle inflammation, and define disease extent. Creatine kinase blood level is often within the normal range and is not useful as a screening test for pyomyositis. Pus aspiration from inflammatory foci establishes the diagnosis, and treatment can be initiated at the same time by aspirative drainage. Blood cultures are rarely positive, but a pus culture could identify the microbial agent of pyomyositis. The causative organism is usually Staphylococcus aureus; the second most common cause is group A Streptococcus. In this issue of the Southern Medical Journal, Hull et al report a case from a temperate region with two rare features; pyomyositis involving a 10-year-old boy and a very rare etiology, Streptococcus agalactiae. To the best of our knowledge, there are only 5 published cases of S agalactiae to date. This situation, however, could be related to increasing recognition of group B streptococcal infection in individuals with serious underlying diseases, such as diabetes mellitus, malignancy, and HIV infection. In summary, the case reported by Hull et al supports the need to consider a diagnosis of pyomyositis in HIV-positive patients from temperate regions with undifferentiated fever.

Antimicrobial resistance of Pseudomonas aeruginosa in a Romanian hospital at the dawn of multidrug resistance

Pseudomonas aeruginosa is a clinical and epidemiological significant pathogen involved especially in infections in hospitalized patients, with an increasing antimicrobial resistance over the past few years. Till recently, Romania’s involvement in antimicrobial surveillance networks was weak.1 Therefore, we conducted a study in order to determine the antimicrobial resistance of P. aeruginosa isolated from various clinical specimens. We analyzed the antimicrobial susceptibility profiles of 296 P. aeruginosa strains isolated from patients hospitalized in “Prof. Dr. Matei Bals” National Institute of Infectious Diseases in Bucharest, Romania, between July 1st 2008 and June 30th

An invasive pneumococcal disease during the influenza pandemic successfully treated with ampicillin

We described the case of a 35-year-old man with a history of pulmonary tuberculosis, presented with invasive pneumococcal disease during the influenza pandemic. The patient recovered with ampicillin monotherapy; the differentials and the antibiotic choice for a fully penicillin susceptible strain of

Emerging viral resistance: dealing with uncertainty in human immunodeficiency virus chemoprophylaxis.

The therapeutic decision, a good example for choice theory, can become a hard task when many options exist in the absence of well-defined criteria to support it. The difficulties are greater in infectious diseases, where the treatment or chemoprophylaxis often needs to be initiated in the absence of resistance data concerning the antimicrobial susceptibility of etiological agent(s). This could result in suboptimal therapy increasing the risk of failure due to lack of activity against the etiological agent, or excessive therapy promoting an unnecessary risk of germ resistance. One disease with fast-increasing resistance is human immunodeficiency virus (HIV), due to pressure exercised by multiple drug regimens and high genetic variability of the virus. Levels of transmitted resistance detected in newly HIVdiagnosed patients exceeding 10% are a common feature correlated with antiviral use. In this issue of the Southern Medical Journal, Youmans et al evaluate the primary resistance in South Carolina, finding a high rate of resistance mutation in a population previously considered to be at a lower risk. As the authors mentioned, these data underestimate the real level of transmitted resistance because the tests were not restricted solely to recent infections and were performed on all newly diagnosed patients. Some of these patients had a longer duration of infection (42% diagnosed in acquired immune deficiency syndrome [AIDS] stage), and subsequently had a greater probability to have a wild genotype of HIV. The major risk involved with this increasing problem of resistance transmission is a more difficult and less optimal management of HIV infection. In the absence of resistance data, the success of treatment is less and less predictable. On the therapeutic level, the choice of antiviral regimen in the absence of HIV genotyping data could be ineffective. The cost-effectiveness analysis indicates a 5% regional prevalence of resistance as a threshold to test baseline genotypic HIV resistance for all patients before initiating treatment. The 2008 International AIDS Society-USA guidelines recommend testing all patients in developed countries at the time of diagnosis of HIV-1 infection. In recent years, a HIV-transmitted primary resistance as low as 4% in an area with access to antiretroviral treatment, such as in the recently published Japanese study of Gatanaga et al, is a very rare situation. Unfortunately, genotype data could be a great problem in some developing countries where antiretroviral treatment is already available, but access to molecular diagnosis laboratory facilities is difficult. The great challenge will be the chemoprophylaxis of HIV-1. Unfortunately, resistance data are not available in most situations (unknown, or multiple sources); subsequently, the post-exposure chemoprophylaxis will be performed with a regimen presumed to be active. Also, the new approach of pre-exposure chemoprophylaxis will be conducted virtually entirely in the absence of individual resistance data. At this time, we don’t have studies to indicate an increased risk of failure of chemoprophylaxis due to infection with a (multi)resistant strain of HIV, but such correlation could be presumed. Moreover, the pattern of HIV resistance mutation registers great variations among geographic regions, especially related to differences in the level of consumption for each antiretroviral drug class. A recommendation from one region could be ineffective for another. To alleviate these risks, the proposed regimen needs to include drugs with a high genetic barrier to resistance; the risk of selecting HIV resistance due to chemoprophylaxis could be reduced more effectively with such regimens. The surveillance of a pattern of resistance in defined areas and risk groups could be helpful in order to exclude the drugs with greater probability to be ineffective from local recommended antiviral regimens. The study published in this issue indicates a higher level of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI), with almost 10% of participants, and only 3% resistance to protease inhibitors (PI). These data indicate that it may be a rational option to not include NNRTI in a chemoprophylaxis regimen in South Carolina. Unfortunately, epidemiological data are not available in many parts of the world. To complicate the regimen choice further, many people are moving around, and the source patient could be infected in another region with a different resistance pattern. We need to know which side of the Pyrenees Mountains we’re on, so to speak, in order to decide if a chemoprophylaxis regimen may be active or not. Patient movement and unpredictable resistance are double trouble for HIV chemoprophylaxis. The epidemiological investigations attempting to define these resistance patterns are helpful. Future studies should be tasked with defining the threshold level of resistance at which to drop out a specific antiviral agent. At the same time, we must understand that a unique prophylactic intervention with 100% efficacy will not exist for years, and the role of nonspecific interventions such as safe sex and safe invasive procedures cannot yet be replaced with a worldwide magic bullet. From the Carol Davila University of Medicine, Bucharest, Romania.

Successful oral therapy switch to trimethoprim/sulfamethoxazole in the case of an Enterococcus faecium liver abscess

Sir, The appropriate treatment for liver abscess consists of surgical drainage and antimicrobial therapy, according to the isolated bacteria. Mortality is still high: 8% to 12.8% for a single abscess and 11% to 21% for multiple abscesses, – 3 despite the introduction of guided percutaneous drainage of abscesses and new antibiotics. Enterococcus faecium has been implicated in liver abscess, and its antimicrobial resistance limits therapeutic options. We present a case of a patient with a liver abscess due to E. faecium treated with medical treatment alone, which involved an intravenous to oral switch. A 73-year-old woman was admitted to the infectious diseases department with a 10 day history of fever, chills, nausea and vomiting. She had a history of cholecystectomy with biliaryenteric anastomosis 11 years ago. On the 4th day of the illness, the patient was admitted to the intensive care unit of a district hospital. Laboratory tests showed high C-reactive protein (107 mg/L) and low platelets (96 000/mm). Chest X-ray and abdominal and cardiac ultrasound were normal. She received cefazolin and amikacin. The fever persisted after 6 days of treatment, and she was transferred to the infectious diseases department. Physical examination revealed that she was febrile (38.58C), dehydrated and hypotensive (BP 1⁄4 90/60 mmHg). Laboratory tests confirmed inflammation (C-reactive protein 1⁄4 148 mg/L and procalcitonin .10 ng/mL), high WBCs (19.8 10/L with 88% neutrophils), leucocyturia, slightly elevated aspartate transaminase, 1.44 upper limit of the normal range (ULN), and alkaline phosphatase, 1.32 ULN. Abdominal CT scan showed a 5 cm hypodense area with peripheral enhancement in the seventh hepatic segment, centred on the biliary duct, suggestive of a hepatic abscess and aerobilia. Antimicrobial treatment was switched to imipenem. E. faecium was isolated from urine and blood cultures on the 3rd day, identified with the API System (ATB Expression System, ID32 RapidStrep, bioMerieux, Mercy l’Etoile, France). The strain was susceptible to chloramphenicol, trimethoprim/sulfamethoxazole and teicoplanin and resistant to ampicillin, ampicillin/sulbactam, carbapenems, aminoglycosides (high-level resistance), fluoroquinolones, rifampicin and tetracycline. The antimicrobial treatment was changed to teicoplanin, 400 mg/day after a loading dose of 800 mg on the first day. The patient refused surgical intervention. The patient improved clinically and the blood and urine cultures became negative on day 7; C-reactive protein was 2.7 mg/L on day 25. On day 27, a new CT scan showed a reduction in the liver hypodense area to 2.5 cm in diameter. Teicoplanin was replaced with oral trimethoprim/sulfamethoxazole (10 mg of trimethoprim/kg/day), and the patient was discharged from the hospital the next day. During follow-up, the patient remained apyrexial. Forty days after the patient was discharged, a CT scan showed the complete resolution of the abscess, allowing us to stop the antimicrobial treatment. After 6 months without antibiotic, the patient exhibited no signs of recurrence. The literature is very limited regarding antimicrobial intravenous-to-oral switch therapy for liver abscesses. Most of the antimicrobials that are active against ampicillin-resistant enterococci cannot be given orally; linezolid could be an option for a ‘back up’ therapy, but side effects, costs and the risk of selection of resistant strains are against its prolonged administration. Our patient had risk factors for an infection with resistant bacteria: previous admission to an intensive care unit and inefficient antibiotic treatment; the E. faecium isolate was resistant to b-lactams and fluoroquinolones. Trimethoprim/sulfamethoxazole has activity against Gram-positive bacteria including communityassociated methicillin-resistant Staphylococcus aureus and ampicillin-resistant enterococci. Trimethoprim/sulfamethoxazole efficacy in enterococcal infections is debatable. The selection of resistant bacteria from the normal microflora is a potential risk of its use; however, there is a low selection rate even in immunocompromised patients who receive trimethoprim/ sulfamethoxazole for a long time for pneumocystosis prophylaxis; a report indicated that a 2 year accidental administration of a therapeutic dosage of trimethoprim/sulfamethoxazole had no significant impact on microflora. Data from some areas have shown a 74% to 80% in vitro susceptibility of enterococci to trimethoprim/sulfamethoxazole, as well as therapeutic success with trimethoprim/sulfamethoxazole alone or associated with ciprofloxacin. Our case illustrates that trimethoprim/sulfamethoxazole can be used for the treatment of severe enterococcal infections, with abscess regression and no relapse after 6 months. In such cases, it is difficult to decide how long treatment should be continued, owing to the risk of relapse, estimated as 6.5% to 13.2% in two studies. For patients treated solely with antibiotics, the duration of the therapy could be 2–6 months. Because inflammation markers normalize rapidly, the CT scan surveillance is more useful: the complete resolution of the liver abscess is the sign that usually indicates the moment to stop the treatment. In conclusion, trimethoprim/sulfamethoxazole could be considered for the treatment of susceptible enterococcal infections, especially as oral switch after initial intravenous treatment, as long as other antienterococcal antibiotics for oral administration are not available.