High-risk febrile neutropenia in Auckland 2003-2004: the influence of the microbiology laboratory on patient treatment and the use of pathogen-specific therapy.

BACKGROUND: International guidelines recommend routine microbiological assessment of patients with febrile neutropenia, but do not recommend a change from broad-spectrum antibiotic therapy to pathogen-specific therapy when a clinically relevant organism has been isolated. The aim of the study was to determine the aetiology of febrile neutropenia in adult haematology patients at Auckland City Hospital, to document the changes in treatment made following isolation of a clinically relevant organism and to assess adverse outcomes in any patient who received pathogen-specific therapy after a positive culture result. METHODS: The results of all microbiological tests together with antibiotic therapy were recorded from consecutive patients with fever and a neutrophil count <0.5 x 10(9)/L over 1 year beginning in May 2003. RESULTS: One thousand one hundred and ninety-six specimens were collected from 81 patients during 116 episodes of febrile neutropenia. A pathogen was isolated from blood cultures in 40 episodes: Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for 35%. Isolation of a pathogen from blood cultures resulted in a change of treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes, antibiotic therapy was optimized to a single pathogen-specific agent. No adverse events or subsequent changes in antibiotic therapy occurred in any of these 12 patients. Isolation of a pathogen from specimens other than blood seldom led to a change in therapy. CONCLUSION: Isolation of a pathogen from blood cultures often allows antibiotic therapy to be simplified to a pathogen-specific regimen. Further study of this approach is warranted.

Good outcome in HIV-infected refugees after resettlement in New Zealand: population study.

BACKGROUND: The aims of this study were to determine the clinical characteristics on arrival and the subsequent clinical outcome of HIV-infected UN quota refugees who settled in New Zealand during the last 11 years and to estimate their rate of HIV transmission. METHODS: A population study was conducted. Data were provided by the Mangere Refugee Resettlement Centre, the infectious disease physicians caring for the subjects, the New Zealand AIDS Epidemiology Group and laboratories carrying out HIV viral load assays. RESULTS: One hundred of 7732 (1.3%) UN quota refugees were HIV positive; mean age 30 years, 56% were men, median initial CD4 count was 320 (range 20-1358). HIV infection was most commonly acquired by heterosexual intercourse (74%). The median follow up was 5.0 years (range 1 month to 9.7 years). Five died and 15 subjects had 16 AIDS-defining illnesses, most commonly tuberculosis (n = 10). Sixty subjects commenced highly active antiretroviral therapy of whom 36/59 (61%) had an undetectable HIV viral load after 1 year of treatment. None of the six children born to HIV-infected women in New Zealand were infected. There were two known cases of horizontal transmission of HIV infection. CONCLUSION: Although HIV-infected quota refugees often have to overcome severe social, cultural and financial handicaps, their clinical outcome is generally very good, with response rates to highly active antiretroviral therapy that are similar to other patient groups. Furthermore, they have not been a significant source of transmission of HIV infection after resettlement in New Zealand.

Cefoperazone in Klebsiella meningitis: a case report.

A 51-year-old man with meningitis due to Klebsiella pneumoniae was treated with cefoperazone 6 to 8 g/day intravenously and was cured. Simultaneous blood and cerebrospinal fluid levels were measured. Trough levels of cefoperazone in cerebrospinal fluid were 9 and 12 mg/L. Cefoperazone should be considered for meningitis due to susceptible organisms resistant to customarily used antibacterial drugs.

Cefoperazone in lower respiratory tract infections.

17 hospitalised patients with a wide variety of common lower respiratory tract infections received at least 6 days of intravenous bolus cefoperazone 1.0g 12-hourly. Disease was caused by Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and mixed anaerobes in 1 patient. All isolates were sensitive to cefoperazone. 11 patients were cured, 4 improved, and 2 failed (1 of whom had an anaerobic empyema). Toxicity and side effects were infrequent. In general cefoperazone was effective therapy for these infections.

Cystic hydatid disease in Auckland, New Zealand, 1967-1982.

The development of anthelmintic chemotherapy has provoked re-evaluation of the management of hydatid disease. We reviewed the case records of 74 patients with 93 episodes admitted to hospitals in Auckland, New Zealand, between 1967 and 1982. Median stay was 29 d (range 1-172). 46 (62%) of the patients were male: 34 (45%) were European and 38 (51%) Maori. The median age was 39 years (range 14-85). The majority of patients presented with symptoms and signs related to local effects of the cyst. 57 (77%) patients had at least one operation and while 34 (60%) had a major surgical complication, only 3 died. At follow-up in 1984, 38 (67%) of the surgical patients and 10 of the 17 (65%) who were not operated on were alive. 9 mebendazole recipients were evaluated: 5 (55%) responded symptomatically, but only one was cured by mebendazole alone. One stopped mebendazole because of side-effects. 2 patients took albendazole: one was cured and one had a symptomatic response. Thus surgery is not always needed. The role of chemotherapy requires further evaluation.

Recurrent skin infection with Rhodococcus in an immunosuppressed patient.

A renal transplant patient taking prednisone and azathioprine has had repeated episodes of skin infection with the soil saphrophyte Rhodococcus. Human disease with this organism has not been proved before. Although the lesions have always responded to antibiotics, frequent recurrence makes the long-term outlook uncertain.

The effects of World Health Organization chemotherapy on imported leprosy in Auckland, New Zealand, 1983-90.

Between January 1983 and December 1990 in Auckland, New Zealand, 87 patients (28 paucibacillary disease (PBD) and 59 multibacillary disease (MBD)) commenced WHO multidrug therapy (MDT). All were immigrants from the Pacific Islands (65) or Asia (22). A total of 57 patients had already received non-WHO regimens, some continuously, but often intermittently, for many years; 30 patients received WHO MDT only. By December 1990, 50 had completed treatment, with 1 relapse and 1 late reaction, both in patients with PBD treated with WHO MDT only. There have been no relapses in those treated with WHO MDT after prior leprosy treatment. In those with MBD, type II leprosy reactions were less common (16%) in those treated only with WHO MDT than in those treated continuously before 1983 with older regimens (64%). Type I leprosy reactions occurred in about 20% of both these groups. The bacterial index fell faster in those who had had a prolonged prior treatment beginning WHO MDT than in those starting WHO MDT as their initial leprosy chemotherapy. Overall we found WHO MDT was well accepted and the compliance good, but 13 patients (15%) left Auckland before treatment was completed and 6 (7%) during follow up.

New challenges in infectious diseases.

Predicting the behaviour of infectious disease is particularly difficult because it is inextricably linked with microbial mutation and the potentially rapid expression of that change. Nevertheless, the dominant issue in infectious disease in New Zealand into the 1990s, and perhaps in all medicine, is the impact of the spread of HIV infection. Many other new agents and new causes for old familiar syndromes have also been unearthed in recent years and will continue to be so. We need to continue to explore aetiology, mechanisms of prevention and treatment for both the old and the new infectious diseases. Optimal vaccine delivery to those who most need it is a continuing challenge. New vaccines coming will complicate this. In treatment there has been a refreshing shift from chemotherapy to alternative approaches, perhaps summarised as attempts to enhance host immunity. All these treatments will need to be evaluated, and potentially uncomfortable cost benefit decisions made about the relative needs of all these competing costs in our health service. There are enormous research implications in this for basic scientists, laboratory microbiologists, infectious disease physicians and those in community health.

Tuberculosis in those with HIV infection.

AIMS: To determine the incidence, demography, clinical features, treatments and outcome for patients with tuberculosis and human immunodeficiency virus (HIV) infection in Auckland. METHODS: We reviewed the notes of all patients with HIV infection and tuberculosis seen by the Infectious Disease Unit, at Auckland Hospital since the onset of the HIV epidemic in New Zealand in 1984 until 31 December 1995. RESULTS: Eleven patients have had HIV infection and tuberculosis, 2.4% of all those with HIV infection cared for by this unit. Ten were male and eight homosexual. The median age was 30 years (range 24-57). The incidence in Pakeha was 1.2% (3 of 234), in Maori 20% (5 of 25) and in African 27% (3 of 11). Until 1990 we saw one case every two years and since then one or two cases per year. Six patients had normal chest x-rays and five had abnormal chest x-rays; of the latter, three were typical of tuberculosis and two atypical. Ten of the eleven strains of Mycobacterium tuberculosis cultured were fully sensitive but one was resistant to both rifampicin and isoniazid. Conventional treatment regimens were used. Seven patients have died of HIV infection, three continue treatment and one returned to Africa. One patient relapsed with fully sensitive tuberculosis. Three patients had major side effects to rifampicin necessitating alternative treatment. CONCLUSIONS: Tuberculosis is uncommon amongst those with HIV infection in Auckland but the incidence has risen in recent years. The risks amongst Maori and Africans are high. Multidrug resistant tuberculosis is uncommon. Those caring for patients with tuberculosis need to be mindful of HIV infection: those caring for patients with HIV infection need to be increasingly alert for tuberculosis.

Imported malaria in adults in Auckland.

Malaria is an increasing hazard of tropical travel. Sixty-five cases were notified to the Health Department in 1980 and there is clear evidence of under notification. We reviewed the notes of 19 adults admitted to the infectious disease unit, Auckland Hospital, between 1 January 1979 and 31 March 1982. The typical patient admitted is a young caucasian New Zealander presenting three months after returning from Papua New Guinea where he took prophylaxis: he is febrile, infected with P. vivax, has splenomegaly but is not anaemic. Others presented atypically, especially with the potentially lethal P. falciparum. Four patients are described to highlight particular aspects of malaria management. Suggestions for prophylaxis and therapy are made in the light of changing global patterns of resistance of plasmodia, and particularly of P. falciparum to chloroquine.

A clinical and aetiological study of adult patients hospitalised for acute diarrhoeal disease.

Sixty adult patients with diarrhoea discharged from the infectious disease unit, Auckland Hospital in the 15 months from 1 January 1980 were reviewed. Thirty had diarrhoea due to enteric organisms (Campylobacter fetus 8, Shigella 6, Salmonella typhi 4, Salmonella typhimurium 4, Clostridium difficile causing pseudomembranous colitis 3). Other diagnoses included ulcerative colitis and a colonic carcinoma. Eighteen had no specific diagnosis. Combinations of admission fever, faecal leucocytes and leucocytosis increased the likelihood of definitive diagnosis as did prolonged diarrhoea (less than five days) in hospital. A median 3 stools per patient was examined microbiologically: in only six did a second positive follow an initial negative specimen. We now recommend only two stool specimens be examined routinely for diagnosis of enteric bacterial infection. Antibacterial drugs are infrequently needed for adult enteric bacterial diarrhoea (we treated five of 23 in hospital). Local practitioners also manage adult diarrhoea conservatively with only six of 60 patients taking antibacterials as treatment for their diarrhoea before admission.

The spectrum of systemic candidiasis at Auckland Hospital.

Systemic candidiasis is uncommon. We reviewed our experience with this disease from the infectious disease unit, Auckland Hospital, between 1982 and 1988, because many of these patients are referred to us. We then selected 11 of them to highlight particular presentations, diagnostic or management issues. We included both compromised and noncompromised patients from medical and surgical services. Candida albicans was the most common cause, but we also saw patients infected with C glabrata, C parapsilosis, and C tropicalis and present them to exemplify their different clinical presentations. Demonstrable fungaemia is uncommon in patients with systemic candidiasis, serological techniques are both insensitive and nonspecific and patients are often too ill from underlying disease to allow for invasive diagnostic procedures. Thus diagnosis is often difficult. Parenteral amphotericin B with or without 5-fluorocytosine is still the main antifungal treatment. Triazole antifungals may change that in the future. Systemic candidiasis retains a high mortality: careful individualised management of patients may improve mortality and morbidity.

Neurological disease in patients with human immunodeficiency virus infection.

We followed prospectively all patients with HIV infection admitted to the infectious diseases ward at Auckland Hospital over a seven month period. Neurological manifestations of HIV infection were the primary reason for admission in 18 of the 55 patients (33%). Diagnoses were usually presumptive, based on history, clinical findings, radiological appearances and response to empirical therapy. Eight patients had cerebral toxoplasmosis, three primary cerebral lymphoma, two cytomegalovirus retinitis, two HIV neuropathy, one cryptococcal meningitis, one HIV encephalopathy, and one HIV meningitis. Another patient with HIV infection was admitted to the neurology ward at Auckland Hospital with HIV myelopathy during the same seven month period. The median survival of the patients treated for presumptive toxoplasmosis was 7.5 months. Only two patients had not developed AIDS, one having HIV meningitis and the other HIV myelopathy, and in both, symptoms resolved spontaneously with no relapse at one year follow up. The spectrum of neurological manifestations of HIV infection is wide. Investigations to determine the most likely diagnosis are indicated and specific therapy may lead to both excellent palliation and prolonged survival.

Murine typhus in Kaukapakapa?

We report a patient who had not been outside New Zealand with a fever and maculopapular rash. Serology suggested acute murine typhus due to R typhi. This is the first reported case in New Zealand from a nontraveller.

Salmonella typhi infection in adults is not limited to travellers returning from the tropics.

We reviewed the case notes of 23 adult patients infected with Salmonella typhi and admitted to the infectious disease unit, Auckland Hospital between January 1977 and December 1984. Fifteen had typhoid fever and eight were chronic carriers of S typhi. All isolates were sensitive to amoxycillin, chloramphenicol and cotrimoxazole. Ten of those with typhoid fever had recently been in tropical countries, predominantly Pacific Islands. The remaining five all lived in South Auckland and had not travelled out of New Zealand: we suspect that contaminated shellfish collected from the Manukau Harbour in South Auckland were the source. Typhoid fever should be suspected in young travellers returning to New Zealand with fever, diarrhoea, abdominal pain and headache. Similarly this diagnosis should be suspected in Polynesians and Maoris from South Auckland who have not travelled. All but one patient with typhoid fever responded clinically to the initial regimen which was usually oral amoxycillin given for a median 18 days. One other patient relapsed. Cholescystectomy and subsequent oral antibacterials eradicated S typhi from five biliary carriers with abnormal gallbladders. Prolonged high dose oral amoxycillin alone was effective in one of two carrier patients with normal gallbladders. The role of the Department of Health in identifying carriers of S typhi remains important.

Early clinical experience with imipenem-cilistatin.

We treated 15 patients with 16 proven bacterial infections with imipenem-cilistatin. Nine isolates were gram positive cocci, the remaining ten being gram negative bacilli and all had MICs less than or equal to 2.0 mg/l. Eight patients had respiratory tract infections, four urinary tract infections and there were three others. Twelve of 16 infections were microbiologically cured. There were no important drug side effects or toxicity. Imipenem-cilistatin is a potentially useful formulation.

Imported malaria in Auckland in 1993.

AIM: To determine the number of people with malaria in Auckland in 1993 and determine species, sources, exposure history, use of chemoprophylaxis, outcome and geographic attack rates. METHODS: We prospectively obtained the numbers of people with laboratory diagnosed malaria from all haematology departments in Auckland and then contacted the patients and their doctors to elicit further details. RESULTS: Forty three people, 30 men and 13 women, had malaria. Twenty eight were New Zealanders, 10 migrants, three temporary visitors and two not determined. Thirty two had P vivax infection, 11 P falciparum: none had complications. The highest attack rate was in travellers to the Solomon Islands. Eighty two per cent took prophylaxis. CONCLUSIONS: Malaria is an uncommon diagnosis in Auckland. Most patients took prophylaxis. The disease is undernotified. No one died of malaria in 1993 in Auckland.

Human immunodeficiency virus infection in women in Auckland: an evolving epidemic.

AIMS: To study the epidemiology, presenting features and outcome of HIV infection among women in Auckland. METHODS: Retrospective review of the medical records of all HIV infected women cared for by the adult infectious disease unit or the sexual health clinic at Auckland Hospital up to the end of December, 1993. RESULTS: Thirty women with HIV infection were cared for between September 1986 and December 1993. Heterosexual intercourse, often with a man from a country with endemic heterosexual HIV transmission, was the most common means of acquiring HIV infection. Late diagnosis of infection probably contributed to the brief median survival seen in the nine women who developed AIDS. CONCLUSIONS: Increased education is necessary to inform women about the risks of acquiring HIV infection. This education should encourage safer sexual behaviour and the use of needle exchange programmes to minimise the growth of this epidemic.

Experience with pneumocystis carinii pneumonia in patients with AIDS.

We have reviewed admission data, some diagnostic tests, treatment and outcome of 31 male homosexual patients infected with the human immunodeficiency virus with 37 consecutive episodes of presumptive Pneumocystis carinii pneumonia treated at the infectious disease unit, Auckland Hospital, between 1985 and 30 June 1988. The median age was 39 years. Eight episodes were proven Pneumocystis carinii pneumonia, 18 satisfied Centres for Disease Control criteria for presumptive Pneumocystis carinii pneumonia and 11 lacked one Centres for Disease Control criterion. Patients began intravenous or oral cotrimoxazole in 32 episodes, initially 20 mg/k/d of trimethoprim component, but since early 1988 10 mg/k/d. In nine episodes treatment was changed to intravenous pentamidine because of side effects or failure to respond while five received pentamidine as their only drug. Cotrimoxazole caused side effects in 20 of 32 episodes (rash in 11) and pentamidine in 10 of 14 (renal impairment in nine). Two patients died (ie, a 5% mortality for all 37 episodes or 8% for 26 proven and Centres for Disease Control presumptive episodes). Median hospital stay for survivors was 11 days. Fourteen other patients have subsequently died a median eight months after the initial episode. Pneumocystis carinii pneumonia is an important infection in patients infected with the human immunodeficiency virus.

The evidence for rickettsial disease arising in New Zealand.

AIM: To describe the first cases of serologically proven riskettsial disease reported in non-travelling New Zealanders. METHODS: We used clinical and laboratory based surveillance, review of clinical records and patient interviews. Information collected included demographics, presenting signs and symptoms, laboratory results, treatment and outcome. A limited seroprevalence study of rural-living friends and relatives was performed. We tested for rickettsial antibodies in the sera of possums trapped on properties close to the area of residence of the first two cases. RESULT: Serological results support the diagnosis of a rickettsial disease in nine patients. Clinical findings at presentation were nonspecific but included fever, rigors and headache. A rash was noted in four (44%). All had abnormal liver enzymes. Eight were hospitalised. No patient died but two were admitted to intensive care. CONCLUSIONS: There is strong clinical and serological evidence that Rickettsia typhi (the causative organism of murine typhus) or a Rickettsia typhi-like organism is present in the greater Auckland region. To prove it, the organism will need to be cultured or rickettsial DNA detected by molecular methods. Rickettsial infection needs to be included in the differential diagnosis of patients presenting with fever, headache and myalgia, particularly in those with rural lifestyles at least in the greater Auckland area.